Toxics

11 pages, 2673 KiB

Open AccessArticle

Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells

by Joseph H. Lucas, Qixin Wang, Thivanka Muthumalage and Irfan Rahman

Toxics 2021, 9(6), 144; https://doi.org/10.3390/toxics9060144 - 19 Jun 2021

Cited by 8 | Viewed by 2686

Multi-walled carbon nanotubes are engineered nanomaterials (ENMs) that have a fiber-like structure which may be a concern for the development of cellular senescence. Premature senescence, a state of irreversible cell cycle arrest, is implicated in the pathogenesis of chronic lung diseases such as [...] Read more.

Multi-walled carbon nanotubes are engineered nanomaterials (ENMs) that have a fiber-like structure which may be a concern for the development of cellular senescence. Premature senescence, a state of irreversible cell cycle arrest, is implicated in the pathogenesis of chronic lung diseases such as pulmonary fibrosis (PF). However, the crosstalk between downstream pathways mediating fibrotic and senescent responses of MWCNTs is not well-defined. Here, we exposed human bronchial epithelial cells (BEAS-2B) to MWCNTs for up to 72 h and demonstrate that MWCNTs increase reactive oxygen species (ROS) production accompanied by inhibition of cell proliferation. In addition, MWCNT exposure resulted in the increase of p21 protein abundance and senescence associated β-galactosidase (SA β-gal) activity. We also determined that co-exposure with the cytokine, transforming growth factor-β (TGF-β) exacerbated cellular senescence indicated by increased protein levels of p21, p16, and γH2A.X. Furthermore, the production of fibronectin and plasminogen activator inhibitor (PAI-1) was significantly elevated with the co-exposure compared to MWCNT or TGF-β alone. Together, our study suggests that the cellular senescence potential of MWCNTs may be enhanced by pro-fibrotic mediators, such as TGF-β in the surrounding microenvironment. Full article

(This article belongs to the Section Toxicology)

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17 pages, 7851 KiB

Open AccessReview

Recent Advances in Colorimetric Detection of Arsenic Using Metal-Based Nanoparticles

by Haradhan Kolya, Kazuharu Hashitsume and Chun-Won Kang

Toxics 2021, 9(6), 143; https://doi.org/10.3390/toxics9060143 - 17 Jun 2021

Cited by 25 | Viewed by 6096

Abstract

Nowadays, arsenic (III) contamination of drinking water is a global issue. Laboratory and instrument-based techniques are typically used to detect arsenic in water, with an accuracy of 1 ppb. However, such detection methods require a laboratory-based environment, skilled labor, and additional costs for [...] Read more.

Nowadays, arsenic (III) contamination of drinking water is a global issue. Laboratory and instrument-based techniques are typically used to detect arsenic in water, with an accuracy of 1 ppb. However, such detection methods require a laboratory-based environment, skilled labor, and additional costs for setup. As a result, several metal-based nanoparticles have been studied to prepare a cost-effective and straightforward detector for arsenic (III) ions. Among the developed strategies, colorimetric detection is one of the simplest methods to detect arsenic (III) in water. Several portable digital detection technologies make nanoparticle-based colorimetric detectors useful for on-site arsenic detection. The present review showcases several metal-based nanoparticles that can detect arsenic (III) colorimetrically at a concentration of ~0.12 ppb or lower in water. A literature survey suggests that biomolecule-based metal nanoparticles could serve as low-cost, facile, susceptible, and eco-friendly alternatives for detecting arsenic (III). This review also describes future directions, perspectives and challenges in developing this alternative technology, which will help us reach a new milestone in designing an effective arsenic detector for commercial use. Full article

(This article belongs to the Section Environmental Chemistry)

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26 pages, 509 KiB

Open AccessReview

Mechanisms of Metal-Induced Mitochondrial Dysfunction in Neurological Disorders

by Hong Cheng, Bobo Yang, Tao Ke, Shaojun Li, Xiaobo Yang, Michael Aschner and Pan Chen

Toxics 2021, 9(6), 142; https://doi.org/10.3390/toxics9060142 - 17 Jun 2021

Cited by 33 | Viewed by 4695

Abstract

Metals are actively involved in multiple catalytic physiological activities. However, metal overload may result in neurotoxicity as it increases formation of reactive oxygen species (ROS) and elevates oxidative stress in the nervous system. Mitochondria are a key target of metal-induced toxicity, given their [...] Read more.

Metals are actively involved in multiple catalytic physiological activities. However, metal overload may result in neurotoxicity as it increases formation of reactive oxygen species (ROS) and elevates oxidative stress in the nervous system. Mitochondria are a key target of metal-induced toxicity, given their role in energy production. As the brain consumes a large amount of energy, mitochondrial dysfunction and the subsequent decrease in levels of ATP may significantly disrupt brain function, resulting in neuronal cell death and ensuing neurological disorders. Here, we address contemporary studies on metal-induced mitochondrial dysfunction and its impact on the nervous system. Full article

(This article belongs to the Special Issue Neurotoxicity of Environmental Metal Toxicants)

15 pages, 1772 KiB

Open AccessArticle

Particle-Bound Mercury Characterization in the Central Italian Herbarium of the Natural History Museum of the University of Florence (Italy)

by Francesco Ciani, Laura Chiarantini, Pilario Costagliola and Valentina Rimondi

Toxics 2021, 9(6), 141; https://doi.org/10.3390/toxics9060141 - 15 Jun 2021

Cited by 3 | Viewed by 2598

Abstract

Museums air quality can be negatively affected by treatments with heavy metals compounds employed to prevent pest infestations. Among these, the past use of mercury dichloride (HgCl₂) on herbaria artifacts currently produces high levels of indoor atmospheric gaseous mercury (Hg⁰ [...] Read more.

Museums air quality can be negatively affected by treatments with heavy metals compounds employed to prevent pest infestations. Among these, the past use of mercury dichloride (HgCl₂) on herbaria artifacts currently produces high levels of indoor atmospheric gaseous mercury (Hg⁰) and possibly of particulate bound Hg (PBM), i.e., the particulate matter containing Hg. This study evaluates the PBM pollution in the Central Italian Herbarium (Natural History Museum of the University of Florence, Italy), characterizing the size range and chemical speciation with SEM-EDS microanalysis. The analysis of the total Hg concentration in the samples allowed to calculate the workers exposure risk to this pollutant. PBM is almost totally classifiable as fine particulate with a significant dimensional increase in a period of scarce attendance of the Herbarium rooms. The microanalysis indicates that Hg is essentially bound to S, highlighting the change of Hg speciation from the original association with Cl. The average Hg concentration reveals a potential health risk for workers as result of multiple Hg exposure pathways, mainly by ingestion. The study provides information for characterizing PBM pollution that could affect a workplace atmosphere and a useful basis to evaluate and correctly design solution strategies to reduce the contamination levels and protect workers’ health. Full article

(This article belongs to the Special Issue Mercury Cycling and Potential Impacts on Ecosystems and Human Health: Current Research and Emerging Trends)

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18 pages, 1074 KiB

Open AccessReview

Estimation of the Inhaled Dose of Pollutants in Different Micro-Environments: A Systematic Review of the Literature

by Francesca Borghi, Andrea Spinazzè, Simone Mandaglio, Giacomo Fanti, Davide Campagnolo, Sabrina Rovelli, Marta Keller, Andrea Cattaneo and Domenico Maria Cavallo

Toxics 2021, 9(6), 140; https://doi.org/10.3390/toxics9060140 - 12 Jun 2021

Cited by 17 | Viewed by 3514

Abstract

Recently, the need to assess personal exposure in different micro-environments has been highlighted. Further, estimating the inhaled dose of pollutants is considerably one of the most interesting parameters to be explored to complete the fundamental information obtained through exposure assessment, especially if associated [...] Read more.

Recently, the need to assess personal exposure in different micro-environments has been highlighted. Further, estimating the inhaled dose of pollutants is considerably one of the most interesting parameters to be explored to complete the fundamental information obtained through exposure assessment, especially if associated with a dose-response approach. To analyze the main results obtained from the studies related to the estimation of the inhaled dose of pollutants in different micro-environments (environments in which an individual spends a part of his day), and to identify the influence of different parameters on it, a systematic review of the literature was performed. The principal outcomes from the considered studies outlined that (i) exposure concentration and residence time are among the most important parameters to be evaluated in the estimation of the inhaled dose, especially in transport environments. Further, (ii) the pulmonary ventilation rate can be of particular interest during active commuting because of its increase, which increases the inhalation of pollutants. From a methodological point of view, the advent of increasingly miniaturized, portable and low-cost technologies could favor these kinds of studies, both for the measurement of atmospheric pollutants and the real-time evaluation of physiological parameters used for estimation of the inhaled dose. The main results of this review also show some knowledge gaps. In particular, numerous studies have been conducted for the evaluation (in terms of personal exposure and estimation of the inhaled dose) of different PM fractions: other airborne pollutants, although harmful to human health, are less represented in studies of this type: for this reason, future studies should be conducted, also considering other air pollutants, not neglecting the assessment of exposure to PM. Moreover, many studies have been conducted indoors, where the population spends most of their daily time. However, it has been highlighted how particular environments, even if characterized by a shorter residence time, can contribute significantly to the dose of inhaled pollutants. These environments are, therefore, of particular importance and should be better evaluated in future studies, as well as occupational environments, where the work results in a high pulmonary ventilation rate. The attention of future studies should also be focused on these categories of subjects and occupational studies. Full article

(This article belongs to the Section Exposome Analysis and Risk Assessment)

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13 pages, 2977 KiB

Open AccessArticle

The Potential for PE Microplastics to Affect the Removal of Carbamazepine Medical Pollutants from Aqueous Environments by Multiwalled Carbon Nanotubes

by Xiaoyu Sheng, Junkai Wang, Wei Zhang and Qiting Zuo

Toxics 2021, 9(6), 139; https://doi.org/10.3390/toxics9060139 - 12 Jun 2021

Cited by 12 | Viewed by 3330

Abstract

Microplastics are ubiquitous in aquatic environments and interact with other kinds of pollutants, which affects the migration, transformation, and fate of those other pollutants. In this study, we employ carbamazepine (CBZ) as the contaminant to study the influence of polyethylene (PE) microplastics on [...] Read more.

Microplastics are ubiquitous in aquatic environments and interact with other kinds of pollutants, which affects the migration, transformation, and fate of those other pollutants. In this study, we employ carbamazepine (CBZ) as the contaminant to study the influence of polyethylene (PE) microplastics on the adsorption of CBZ pollutants by multiwalled carbon nanotubes (MCNTs) in aqueous solution. The adsorption capacity of CBZ by MCNTs in the presence of PE microplastics was obviously lower than that by MCNTs alone. The influencing factors, including the dose of microplastics, pH, and CBZ solution concentration, on the adsorption of CBZ by MCNTs and MCNTs−PE were thoroughly investigated. The adsorption rate of CBZ by MCNTs decreased from 97.4% to 90.6% as the PE microplastics dose increased from 2 g/L to 20 g/L. This decrease occurred because the MCNTs were coated on the surface of the PE microplastics, which further decreased the effective adsorption area of the MCNTs. This research provides a framework for revealing the effect of microplastics on the adsorption of pollutants by carbon materials in aqueous environments. Full article

(This article belongs to the Special Issue New Technologies to Decontaminate Pollutants in Water)

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11 pages, 1297 KiB

Open AccessArticle

Necessity of Assessing Biological Exposure to Arsenic Species by Two Representative Analytical Methods

by Jeong-Wook Seo and Young-Seoub Hong

Toxics 2021, 9(6), 138; https://doi.org/10.3390/toxics9060138 - 11 Jun 2021

Cited by 4 | Viewed by 2368

Abstract

Arsenic (As) exists as highly toxic chemical species. Chronic exposure to its inorganic form can cause multiple organ failure and skin cancer in humans, warranting the need to determine the toxicity of each chemical species. This study evaluated the proportions of exposure to [...] Read more.

Arsenic (As) exists as highly toxic chemical species. Chronic exposure to its inorganic form can cause multiple organ failure and skin cancer in humans, warranting the need to determine the toxicity of each chemical species. This study evaluated the proportions of exposure to four chemical species of As (cAs), namely arsenite (AsIII), arsenate (AsV), monomethylarsinic acid (MMA), and dimethylarsenic acid (DMA), and it confirmed the necessity of evaluating biological exposure to cAs. Urine samples were collected from 457 subjects residing near 103 abandoned metal mines. Hydride generation atomic absorption spectroscopy (HG-AAS) was performed to measure the combined concentration of four cAs (hAs_AAS). High-performance liquid chromatography and inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) were performed to determine the concentrations of the individual cAs and the sum of the four cAs (hAs_ICP). The proportions of AsV and MMA were relatively higher in the low-hAs_ICP concentration section. These findings suggest that hAs_AAS, which is mainly used for its cost-efficiency, is limited for evaluating exposure. Though hAs_AAS was found to exist in a low concentration, highly toxic AsV and MMA could be observed in high concentrations. Therefore, HPLC-ICP-MS is recommended for assessing cAs in environmentally vulnerable areas such as abandoned metal mines. Full article

(This article belongs to the Special Issue Biomonitoring of Human Exposure: From Individual to Group Exposure Assessment)

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18 pages, 1674 KiB

Open AccessArticle

Acute and Cumulative Effects of Repeated Exposure to Chlorpyrifos on the Liver and Kidney Function among Egyptian Adolescents

by Ahmed A. Ismail, Olfat Hendy, Gaafar Abdel Rasoul, James R. Olson, Matthew R. Bonner and Diane S. Rohlman

Toxics 2021, 9(6), 137; https://doi.org/10.3390/toxics9060137 - 10 Jun 2021

Cited by 11 | Viewed by 3069

Abstract

Background: There is a paucity of research that tracks changes in liver and kidney function among pesticide applicators. The aim of the current study was to investigate the role of repeated seasonal exposure to the organophosphorus pesticide, chlorpyrifos, on serum measures of liver [...] Read more.

Background: There is a paucity of research that tracks changes in liver and kidney function among pesticide applicators. The aim of the current study was to investigate the role of repeated seasonal exposure to the organophosphorus pesticide, chlorpyrifos, on serum measures of liver and kidney function. Methods: Pesticide exposure was assessed by measuring the urinary concentrations of 3,5,6-trichloro-2 pyridinol (TCPy), a specific biomarker for chlorpyrifos. Chlorpyrifos exposure and 8 serum markers of liver and kidney function were measured at 15 timepoints over 3 years prior to, during, and following the end of seasonal pesticide application among adolescent applicators and non-applicators from 4 field stations in Menoufia, Egypt. Results: Urinary TCPy levels showed increases during the application cycles and recovery at the end of each application season. Altered serum markers of liver and kidney function were associated with chlorpyrifos exposure, with some markers recovering 3 months after the end of exposure each year, while other measures demonstrated progressive increase up to 300% the baseline levels at the end of 3 years. Conclusion: The study demonstrated that frequent assessment of liver and kidney function is a sound practice to evaluate cellular injury following chronic repeated occupational and environmental exposure to chlorpyrifos. Full article

(This article belongs to the Special Issue Pesticides: An update of Exposure and Toxicity)

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20 pages, 2328 KiB

Open AccessFeature PaperArticle

A Quantitative ¹H NMR Method for Screening Cannabinoids in CBD Oils

by Ines Barthlott, Andreas Scharinger, Patricia Golombek, Thomas Kuballa and Dirk W. Lachenmeier

Toxics 2021, 9(6), 136; https://doi.org/10.3390/toxics9060136 - 10 Jun 2021

Cited by 21 | Viewed by 6281

Abstract

Toxicologically relevant levels of the psychoactive ∆⁹-tetrahydocannabinol (∆⁹-THC) as well as high levels of non-psychoactive cannabinoids potentially occur in CBD (cannabidiol) oils. For consumer protection in the fast-growing CBD oil market, facile and rapid quantitative methods to determine the [...] Read more.

Toxicologically relevant levels of the psychoactive ∆⁹-tetrahydocannabinol (∆⁹-THC) as well as high levels of non-psychoactive cannabinoids potentially occur in CBD (cannabidiol) oils. For consumer protection in the fast-growing CBD oil market, facile and rapid quantitative methods to determine the cannabinoid content are crucial. However, the current standard method, i.e., liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS), requires a time-consuming multistep sample preparation. In this study, a quantitative nuclear magnetic resonance spectroscopy (qNMR) method for screening cannabinoids in CBD oils was developed. Contrary to the HPLC-MS/MS method, this qNMR features a simple sample preparation, i.e., only diluting the CBD oil in deuterochloroform. Pulse length-based concentration determination (PULCON) enables a direct quantification using an external standard. The signal intensities of the cannabinoids were enhanced during the NMR spectra acquisition by means of multiple suppression of the triglycerides which are a major component of the CBD oil matrix. The validation confirmed linearity for CBD, cannabinol (CBN), ∆⁹-THC and ∆⁸-THC in hemp seed oil with sufficient recoveries and precision for screening. Comparing the qNMR results to HPLC-MS/MS data for 46 commercial CBD oils verified the qNMR accuracy for ∆⁹-THC and CBD, but with higher limits of detection. The developed qNMR method paves the way for increasing the sample throughput as a complementary screening before HPLC-MS/MS. Full article

(This article belongs to the Topic Instrumental and Bioanalytical Methods for Food Contaminant Detection)

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18 pages, 2403 KiB

Open AccessFeature PaperArticle

Food Contaminants Effects on an In Vitro Model of Human Intestinal Epithelium

by Marion Guibourdenche, Johanna Haug, Noëllie Chevalier, Madeleine Spatz, Nicolas Barbezier, Jérôme Gay-Quéheillard and Pauline M. Anton

Toxics 2021, 9(6), 135; https://doi.org/10.3390/toxics9060135 - 9 Jun 2021

Cited by 7 | Viewed by 4341

Abstract

Pesticide residues represent an important category of food contaminants. Furthermore, during food processing, some advanced glycation end-products resulting from the Maillard reaction can be formed. They may have adverse health effects, in particular on the digestive tract function, alone and combined. We sought [...] Read more.

Pesticide residues represent an important category of food contaminants. Furthermore, during food processing, some advanced glycation end-products resulting from the Maillard reaction can be formed. They may have adverse health effects, in particular on the digestive tract function, alone and combined. We sought to validate an in vitro model of the human intestinal barrier to mimic the effects of these food contaminants on the epithelium. A co-culture of Caco-2/TC7 cells and HT29-MTX was stimulated for 6 h with chlorpyrifos (300 μM), acrylamide (5 mM), N^ε-Carboxymethyllysine (300 μM) alone or in cocktail with a mix of pro-inflammatory cytokines. The effects of those contaminants on the integrity of the gut barrier and the inflammatory response were analyzed. Since the co-culture responded to inflammatory stimulation, we investigated whether this model could be used to evaluate the effects of food contaminants on the human intestinal epithelium. CPF alone affected tight junctions’ gene expression, without inducing any inflammation or alteration of intestinal permeability. CML and acrylamide decreased mucins gene expression in the intestinal mucosa, but did not affect paracellular intestinal permeability. CML exposure activated the gene expression of MAPK pathways. The co-culture response was stable over time. This cocktail of food contaminants may thus alter the gut barrier function. Full article

(This article belongs to the Special Issue Effects of Food Contaminants on Human Health)

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16 pages, 7429 KiB

Open AccessArticle

Effects of Phthalate Esters (PAEs) on Cell Viability and Nrf2 of HepG2 and 3D-QSAR Studies

by Huan Liu, Huiying Huang, Xueman Xiao, Zilin Zhao and Chunhong Liu

Toxics 2021, 9(6), 134; https://doi.org/10.3390/toxics9060134 - 5 Jun 2021

Cited by 10 | Viewed by 3531

Abstract

Phthalate esters (PAEs) are a widespread environmental pollutant, and their ecological and environmental health risks have gradually attracted attention. To reveal the toxicity characteristics of these compounds, ten PAEs were selected as research objects to establish a cell model. CCK-8 was used to [...] Read more.

Phthalate esters (PAEs) are a widespread environmental pollutant, and their ecological and environmental health risks have gradually attracted attention. To reveal the toxicity characteristics of these compounds, ten PAEs were selected as research objects to establish a cell model. CCK-8 was used to determine cell viability, Western blots were used to determine the content of Nrf₂ in HepG2, and the LD₅₀ collected for the 13 PAEs administered to rats. On this basis, 3D-QSAR models of IC₅₀, LD₅₀ and Nrf2 were established. The experimental results showed that as the time of PAEs exposure increased (24, 48 and 72 h), cell viability gradually decreased. The test concentration (62.5 /125/250 μM) of PAEs exposed for 48 h could significantly increase the content of Nrf2, and the 1000 μM PAEs could inhibit the content of Nrf2. The model is relatively stable and predicts well that the introduction of large and hydrophobic groups may significantly affect the toxic effects of PAEs on cells. The present study provided a potential tool for predicting the LD50 and Nrf2 of new PAEs, and provide a reference for the design of new less toxic PAEs in the future. Full article

(This article belongs to the Special Issue Phthalate Exposure: From Quantification to Risk Assessment)

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14 pages, 1142 KiB

Open AccessFeature PaperArticle

Nutritional Evaluation and Risk Assessment of the Exposure to Essential and Toxic Elements in Dogs and Cats through the Consumption of Pelleted Dry Food: How Important Is the Quality of the Feed?

by Ana Macías-Montes, Manuel Zumbado, Octavio P. Luzardo, Ángel Rodríguez-Hernández, Andrea Acosta-Dacal, Cristian Rial-Berriel, Luis D. Boada and Luis Alberto Henríquez-Hernández

Toxics 2021, 9(6), 133; https://doi.org/10.3390/toxics9060133 - 5 Jun 2021

Cited by 11 | Viewed by 5773

Abstract

Dry feed for pets lacks specific legislation regarding maximum residue limits for inorganic elements. The aim of the present study was to determine the content of 43 inorganic elements in dog and cat feed, studying whether there were differences according to the supposed [...] Read more.

Dry feed for pets lacks specific legislation regarding maximum residue limits for inorganic elements. The aim of the present study was to determine the content of 43 inorganic elements in dog and cat feed, studying whether there were differences according to the supposed quality of the food and performing the risk assessment for health. Thirty-one and thirty packages of pelleted dry food for cats and dogs, respectively, were analyzed. After acidic microwave-assisted digestion, elements were detected and quantified by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In general, we did not observe important differences in the content of elements according to the supposed quality of the brand. Among trace elements, selenium and manganese are above the dietary reference value. Arsenic and mercury showed the highest acute hazard indexes, which make them risk factors for the health of dogs and cats. Aluminum, uranium, antimony and vanadium contents were above the toxic reference value and showed the highest acute hazard indexes. It is necessary to improve the legislation regarding the food safety of pets, for their health and to protect the rights of consumers. Full article

(This article belongs to the Special Issue Environmental and Biological Monitoring: Analytical Methods and Assessment)

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27 pages, 3528 KiB

Open AccessReview

Adrenergic and Glucocorticoid Receptors in the Pulmonary Health Effects of Air Pollution

by Myles X. Hodge, Andres R. Henriquez and Urmila P. Kodavanti

Toxics 2021, 9(6), 132; https://doi.org/10.3390/toxics9060132 - 4 Jun 2021

Cited by 9 | Viewed by 7114

Abstract

Adrenergic receptors (ARs) and glucocorticoid receptors (GRs) are activated by circulating catecholamines and glucocorticoids, respectively. These receptors regulate the homeostasis of physiological processes with specificity via multiple receptor subtypes, wide tissue-specific distribution, and interactions with other receptors and signaling processes. Based on their [...] Read more.

Adrenergic receptors (ARs) and glucocorticoid receptors (GRs) are activated by circulating catecholamines and glucocorticoids, respectively. These receptors regulate the homeostasis of physiological processes with specificity via multiple receptor subtypes, wide tissue-specific distribution, and interactions with other receptors and signaling processes. Based on their physiological roles, ARs and GRs are widely manipulated therapeutically for chronic diseases. Although these receptors play key roles in inflammatory and cellular homeostatic processes, little research has addressed their involvement in the health effects of air pollution. We have recently demonstrated that ozone, a prototypic air pollutant, mediates pulmonary and systemic effects through the activation of these receptors. A single exposure to ozone induces the sympathetic–adrenal–medullary and hypothalamic–pituitary–adrenal axes, resulting in the release of epinephrine and corticosterone into the circulation. These hormones act as ligands for ARs and GRs. The roles of beta AR (βARs) and GRs in ozone-induced pulmonary injury and inflammation were confirmed in a number of studies using interventional approaches. Accordingly, the activation status of ARs and GRs is critical in mediating the health effects of inhaled irritants. In this paper, we review the cellular distribution and functions of ARs and GRs, their lung-specific localization, and their involvement in ozone-induced health effects, in order to capture attention for future research. Full article

(This article belongs to the Special Issue Effects of Exposure to Air Pollution on Respiratory Health)

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19 pages, 2077 KiB

Open AccessReview

Nanopesticides in Agriculture: Benefits and Challenge in Agricultural Productivity, Toxicological Risks to Human Health and Environment

by Marco Chaud, Eliana B. Souto, Aleksandra Zielinska, Patricia Severino, Fernando Batain, Jose Oliveira-Junior and Thais Alves

Toxics 2021, 9(6), 131; https://doi.org/10.3390/toxics9060131 - 4 Jun 2021

Cited by 156 | Viewed by 18105

Abstract

Nanopesticides are nanostructures with two to three dimensions between 1 to 200 nm, used to carry agrochemical ingredients (AcI). Because of their unique properties, the loading of AcI into nanoparticles offers benefits when compared to free pesticides. However, with the fast development of [...] Read more.

Nanopesticides are nanostructures with two to three dimensions between 1 to 200 nm, used to carry agrochemical ingredients (AcI). Because of their unique properties, the loading of AcI into nanoparticles offers benefits when compared to free pesticides. However, with the fast development of new engineered nanoparticles for pests’ control, a new type of environmental waste is being produced. This paper describes the nanopesticides sources, the harmful environmental and health effects arising from pesticide exposure. The potential ameliorative impact of nanoparticles on agricultural productivity and ecosystem challenges are extensively discussed. Strategies for controlled release and stimuli-responsive systems for slow, sustained, and targeted AcI and genetic material delivery are reported. Special attention to different nanoparticles source, the environmental behavior of nanopesticides in the crop setting, and the most recent advancements and nanopesticides representative research from experimental results are revised. This review also addresses some issues and concerns in developing, formulating and toxicity pesticide products for environmentally friendly and sustainable agriculture. Full article

(This article belongs to the Special Issue Current Research on the Cytotoxicity of Drugs to Humans and Animals)

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14 pages, 2322 KiB

Open AccessArticle

Daytime Restricted Feeding Modifies the Temporal Expression of CYP1A1 and Attenuated Damage Induced by Benzo[a]pyrene in Rat Liver When Administered before CYP1A1 Acrophase

by Oscar Samuel Ávila-Rosales, Mauricio Díaz-Muñoz, Rafael Camacho-Carranza, Elvia Coballase-Urrutia, José Pedraza-Chaverri, Jorge Omar García-Rebollar and Jesús Javier Espinosa-Aguirre

Toxics 2021, 9(6), 130; https://doi.org/10.3390/toxics9060130 - 4 Jun 2021

Cited by 3 | Viewed by 2567

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate CYP1A1 expression, a gene involved in the biotransformation of benzo[a]pyrene (BaP). The AhR pathway shows daily variations under the control of the circadian [...] Read more.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate CYP1A1 expression, a gene involved in the biotransformation of benzo[a]pyrene (BaP). The AhR pathway shows daily variations under the control of the circadian timing system. Daytime restricted feeding (DRF) entrains the expression of genes involved in the processing of nutrients and xenobiotics to food availability. Therefore, we evaluate if temporal AhR, ARNT, and CYP1A1 hepatic expression in rats are due to light/dark cycles or fasting/feeding cycles promoted by DRF. Our results show that AhR oscillates throughout the 24 h period in DRF and ad libitum feeding rats (ALF), showing maximum expression at the same time points. DRF modified the peak of ARNT expression at ZT5; meanwhile, ALF animals showed a peak of maximum expression at ZT17. An increased expression of CYP1A1 was linked to the meal time in both groups of animals. Although a high CYP1A1 expression has been previously associated with BaP genotoxicity, our results show that, compared with the ALF group, DRF attenuated the BaP-CYP1A1 induction potency, the liver DNA-BaP adducts, the liver concentration of unmetabolized BaP, and the blood aspartate aminotransferase and alanine aminotransferase activities when BaP is administered prior to the acrophase of CYP1A1 expression. These results demonstrate that DRF modifies the ARNT and CYP1A1 expression and protects from BaP toxicity. Full article

(This article belongs to the Section Toxicology)

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13 pages, 2923 KiB

Open AccessArticle

Distribution and Seasonal Variation of Microplastics in Tallo River, Makassar, Eastern Indonesia

by Ega Adhi Wicaksono, Shinta Werorilangi, Tamara S. Galloway and Akbar Tahir

Toxics 2021, 9(6), 129; https://doi.org/10.3390/toxics9060129 - 1 Jun 2021

Cited by 51 | Viewed by 6518

Abstract

Attention towards microplastic (MP) pollution in various environments is increasing, but relatively little attention has been given to the freshwater-riverine environment. As the biggest city in the eastern Indonesia region, Makassar can be a potential source of MP pollution to its riverine area. [...] Read more.

Attention towards microplastic (MP) pollution in various environments is increasing, but relatively little attention has been given to the freshwater-riverine environment. As the biggest city in the eastern Indonesia region, Makassar can be a potential source of MP pollution to its riverine area. This study aimed to determine the spatial trends, seasonal variation, and characteristics of MPs in the water and sediment of Tallo River, as the main river in Makassar. Water samples were collected using a neuston net and sediment samples were collected using a sediment corer. The samples collected contained MPs with an abundance ranging from 0.74 ± 0.46 to 3.41 ± 0.13 item/m³ and 16.67 ± 20.82 to 150 ± 36.06 item/kg for water and sediment samples, respectively. The microplastic abundance in the Tallo River was higher in the dry season and tended to increase towards the lower river segment. Fragments (47.80–86.03%) and lines (12.50–47.80%) were the predominant shapes, while blue (19.49–46.15%) and transparent (14.29–38.14%) were the most dominant color. Polyethylene and polypropylene were the common MP polymers found in the Tallo river. Actions to prevent MP pollution in the Makassar riverine area are needed before MP pollution becomes more severe in the future. Full article

(This article belongs to the Special Issue Microplastics in Aquatic Environments: Occurrence, Distribution and Effects)

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18 pages, 2737 KiB

Open AccessArticle

Role of Macrophages in Cytotoxicity, Reactive Oxygen Species Production and DNA Damage in 1,2-Dichloropropane-Exposed Human Cholangiocytes In Vitro

by Abigail Ekuban, Cai Zong, Frederick Adams Ekuban, Yusuke Kimura, Ryoya Takizawa, Kota Morikawa, Kazuo Kinoshita, Sahoko Ichihara, Seiichiroh Ohsako and Gaku Ichihara

Toxics 2021, 9(6), 128; https://doi.org/10.3390/toxics9060128 - 1 Jun 2021

Cited by 5 | Viewed by 4200

Abstract

1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated organic compound, was extensively used in the past in offset color proof-printing. In 2014, the International Agency for Research on Cancer (IARC) reclassified 1,2-DCP from its initial Group 3 to Group 1. Prior to the reclassification, cholangiocarcinoma was [...] Read more.

1,2-Dichloropropane (1,2-DCP), a synthetic chlorinated organic compound, was extensively used in the past in offset color proof-printing. In 2014, the International Agency for Research on Cancer (IARC) reclassified 1,2-DCP from its initial Group 3 to Group 1. Prior to the reclassification, cholangiocarcinoma was diagnosed in a group of workers exposed to 1,2 -DCP in an offset color proof-printing company in Japan. In comparison with other forms of cholangiocarcinoma, 1,2-DCP-induced cholangiocarcinoma was of early onset and accompanied by extensive pre-cancerous lesions in large bile ducts. However, the mechanism of 1,2-DCP-induced cholangiocarcinoma is poorly understood. Inflammatory cell proliferation was observed in various sites of the bile duct in the noncancerous hepatic tissues of the 1,2-DCP-induced cholangiocarcinoma. The aim of this study was to enhance our understanding of the mechanism of 1,2-DCP-related cholangiocarcinogenesis. We applied an in vitro system to investigate the effects of 1,2-DCP, using MMNK-1 cholangiocytes cultured alone or with THP-1 macrophages. The cultured cells were exposed to 1,2-DCP at 0, 0.1, 0.2, 0.4, and 0.8 mM for 24 h, and then assessed for cell proliferation, cell cytotoxicity, DNA damage, and ROS production. Exposure to 1,2-DCP increased proliferation of MMNK-1 cholangiocytes cultured alone, but not those cultured with macrophages. 1,2-DCP also increased LDH cytotoxicity, DNA damage, and ROS production in MMNK-1 cholangiocytes co-cultured with macrophages but not those cultured alone. 1,2-DCP increased TNFα and IL-1β protein expression in macrophages. The results highlight the role of macrophages in enhancing the effects of 1,2-DCP on cytotoxicity, ROS production, and DNA damage in cholangiocytes. Full article

(This article belongs to the Section Toxicology)

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2 pages, 149 KiB

Open AccessEditorial

Gut Microbiota Manipulation to Mitigate the Detrimental Effects of Environmental Pollutants

by Lianguo Chen

Toxics 2021, 9(6), 127; https://doi.org/10.3390/toxics9060127 - 1 Jun 2021

Cited by 19 | Viewed by 2679

Abstract

The ecotoxicology and human health risks of environmental pollutants are creating global concern, especially in the context of the prevalent and severe contamination of environmental abiotic and biotic compartments [...] Full article

(This article belongs to the Special Issue Dysbiosis of Gut Microbiota by Environmental Pollutants: Implications for Host Health)

13 pages, 685 KiB

Open AccessArticle

Temperature and Aging Affect Glyphosate Toxicity and Fatty Acid Composition in Allonychiurus kimi (Lee) (Collembola)

by June Wee, Yun-Sik Lee, Yongeun Kim, Jino Son and Kijong Cho

Toxics 2021, 9(6), 126; https://doi.org/10.3390/toxics9060126 - 31 May 2021

Cited by 6 | Viewed by 2817

Abstract

Glyphosate is the most used herbicide worldwide, but enormous use of glyphosate has raised concerned about its environmental loadings. Although glyphosate is considered non-toxic, toxicity data for soil non-target organisms according to temperature and aging are scarce. This study examined the toxicity of [...] Read more.

Glyphosate is the most used herbicide worldwide, but enormous use of glyphosate has raised concerned about its environmental loadings. Although glyphosate is considered non-toxic, toxicity data for soil non-target organisms according to temperature and aging are scarce. This study examined the toxicity of glyphosate with the temperature (20 °C and 25 °C) and aging times (0 day and 7 days) in soil using a collembolan species, Allonychiurus kimi (Lee). The degradation of glyphosate was investigated. Fatty acid composition of A. kimi was also investigated. The half-life of glyphosate was 2.38 days at 20 °C and 1.69 days at 25 °C. At 20 °C with 0 day of aging, the EC₅₀ was estimated to be 93.5 mg kg⁻¹. However, as the temperature and aging time increased, the glyphosate degradation increased, so no significant toxicity was observed on juvenile production. The proportions of the arachidonic acid and stearic acid decreased and increased with the glyphosate treatment, respectively, even at 37.1 mg kg⁻¹, at which no significant effects on juvenile production were observed. Our results showed that the changes in the glyphosate toxicity with temperature and aging time were mostly dependent on the soil residual concentration. Furthermore, the changes in the fatty acid compositions suggest that glyphosate could have a chronic effect on soil organisms. Full article

(This article belongs to the Section Ecotoxicology)

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31 pages, 4530 KiB

Open AccessFeature PaperArticle

Which Is More Toxic? Evaluation of the Short-Term Toxic Effects of Chlorpyrifos and Cypermethrin on Selected Biomarkers in Common Carp (Cyprinus carpio, Linnaeus 1758)

by Elenka Georgieva, Vesela Yancheva, Stela Stoyanova, Iliana Velcheva, Ilia Iliev, Tonka Vasileva, Veselin Bivolarski, Eleonora Petkova, Brigitta László, Krisztián Nyeste and László Antal

Toxics 2021, 9(6), 125; https://doi.org/10.3390/toxics9060125 - 31 May 2021

Cited by 27 | Viewed by 4454

Abstract

The general aim of this study was to investigate the negative short-term effects of different concentrations of chlorpyrifos (CPF) and cypermethrin (CYP), based on the EU legislation (MAC-EQS) in common carp (Cyprinus carpio Linnaeus, 1758) under laboratory conditions and to compare their [...] Read more.

The general aim of this study was to investigate the negative short-term effects of different concentrations of chlorpyrifos (CPF) and cypermethrin (CYP), based on the EU legislation (MAC-EQS) in common carp (Cyprinus carpio Linnaeus, 1758) under laboratory conditions and to compare their toxicity. The fish were exposed to the pesticides for 96 h and then different histological and biochemical biomarkers were investigated in the gills and liver, and bioaccumulation analyses were conducted. The chemical studies showed increased pesticide concentrations in the gills as the first site for pollutants compared to the liver at the 96th hour. In addition, the histological analyses showed severe alterations in the gills and liver after exposure to both tested pesticides. In the gills, we found mainly intense proliferative and, to a lesser extent, degenerative changes and alterations in the circulatory system, such as necrosis and vasodilation. In the liver, regressive and progressive lesions, as well as circulatory disturbances and inflammation, were observed. The regressive lesions showed a higher degree of expression compared to the other changes. Furthermore, we found altered enzymatic activities—catalase, glutathione reductase, and glutathione peroxidase—in the liver, compared to the control. Overall, both tested pesticides impacted the studied biomarkers in common carp, even at concentrations lower than those permitted by law. However, the results of the comparative analysis showed a relatively higher toxicity of CYP compared to CPF in the fish. Still, questions persist as to whether the observed changes are adaptive or entirely destructive. To avoid any danger or risk, these pesticides must be applied cautiously, especially near water bodies. Full article

(This article belongs to the Special Issue Impacts of Agrochemicals on Aquatic Ecosystems: Assessing Responses across Biological Scales)

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12 pages, 1824 KiB

Open AccessArticle

Tissue-Specific Distribution of Legacy and Emerging Organophosphorus Flame Retardants and Plasticizers in Frogs

by Yin-E Liu, Xiao-Jun Luo, Ke-Lan Guan, Chen-Chen Huang, Xue-Meng Qi, Yan-Hong Zeng and Bi-Xian Mai

Toxics 2021, 9(6), 124; https://doi.org/10.3390/toxics9060124 - 31 May 2021

Cited by 4 | Viewed by 3021

Abstract

Five types of tissues, including the liver, kidney, intestine, lung, and heart, were collected from black-spotted frogs and bullfrogs to study the tissue-specific accumulation of organophosphorus flame retardants (PFRs) and plasticizers. Thirteen PFRs and nine plasticizers were detected, with average total concentrations of [...] Read more.

Five types of tissues, including the liver, kidney, intestine, lung, and heart, were collected from black-spotted frogs and bullfrogs to study the tissue-specific accumulation of organophosphorus flame retardants (PFRs) and plasticizers. Thirteen PFRs and nine plasticizers were detected, with average total concentrations of 1.4–13 ng/g ww and 858–5503 ng/g ww in black-spotted frogs, 3.6–46 ng/g ww and 355–3504 ng/g ww in bullfrogs. Significant differences in pollutant concentrations among different tissues in the two frog species were found, indicating the specific selectivity distribution of PFRs and plasticizers. Overall, liver tissues exhibited significantly higher pollutant concentrations. The pollutant concentration ratios of other tissue to the sum of liver tissue and other tissues (OLR, C_other/(C_other + C_liver)) corresponding to male frogs were significantly greater than those of females, suggesting that male frogs could have higher metabolic potentials for PFRs and plasticizers. No obvious correlations between OLR and log K_OW were found, indicating that the other factors (e.g., bioaccumulation pathway and metabolism) besides lipophicity could influence the deposition of PFRs and plasticizers in frog livers. Different parental transfer patterns for PFRs and plasticizers were observed in frogs when using different tissues as parental tissues. Moreover, the liver tissues had similar parental transfer mechanism with muscle tissues. Full article

(This article belongs to the Special Issue Fate, Bioaccumulation and Risk Assessments of Persistent Organic Pollutants (POPs))

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17 pages, 5673 KiB

Open AccessArticle

Biosynthesized Iron Oxide Nanoparticles from Petroselinum crispum Leaf Extract Mitigate Lead-Acetate-Induced Anemia in Male Albino Rats: Hematological, Biochemical and Histopathological Features

by Sabry M. El-Bahr, Amal M. Elbakery, Nashwa El-Gazzar, Aziza A. Amin, Saad Al-Sultan, Mohammed A. Alfattah, Saad Shousha, Sameer Alhojaily, Mohammad Shathele, Islam I. Sabeq and Ahlam F. Hamouda

Toxics 2021, 9(6), 123; https://doi.org/10.3390/toxics9060123 - 31 May 2021

Cited by 17 | Viewed by 3442

Abstract

This study aimed to investigate the ameliorative effects of iron oxide nanoparticles (IONPs) prepared from leaf extract of Petroselinum crispum compared to those prepared using a chemical method in lead-acetate-induced anemic rats. Twenty rats were divided into four groups (five rats each). Throughout [...] Read more.

This study aimed to investigate the ameliorative effects of iron oxide nanoparticles (IONPs) prepared from leaf extract of Petroselinum crispum compared to those prepared using a chemical method in lead-acetate-induced anemic rats. Twenty rats were divided into four groups (five rats each). Throughout the experimental period (8 weeks), the rats in group 1 were not given any therapy. The rats in groups 2, 3 and 4 were given 400 ppm lead acetate orally for 2 weeks to make them anemic. Following that, these rats were either left untreated, given 27 ppm of chemical IONPs orally or given 27 ppm of natural IONPs orally for the remaining 6 weeks of the experiment. TEM analysis indicated that the chemically and naturally prepared IONPs had sizes of 6.22–9.7 and 64–68 nm, respectively. Serum ferritin and iron concentrations were reduced, whereas the total iron-binding capacity (TIBC), ALT, AST, urea and creatinine were significantly increased in the non-treated lead-acetate-induced anemic rats compared to those of the control. In addition, congestion, hemorrhage, necrosis, vacuolation and leukocytic infiltration in the kidneys, liver and spleen were observed in non-treated lead-acetate-induced anemic rats compared to the control. The effects of lead acetate were mitigated by IONPs, particularly the natural one. In conclusion, IONPs produced from Petroselinum crispum leaf extract can be used as an efficient and safe therapy in lead-acetate-induced anemic rats. Full article

(This article belongs to the Section Toxicology)

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13 pages, 1093 KiB

Open AccessFeature PaperArticle

Large-Scale Spraying of Roads with Water Contributes to, Rather Than Prevents, Air Pollution

by Fengzhu Tan, Yuming Guo, Wei Zhang, Xingyan Xu, Ming Zhang, Fan Meng, Sicen Liu, Shanshan Li and Lidia Morawska

Toxics 2021, 9(6), 122; https://doi.org/10.3390/toxics9060122 - 28 May 2021

Cited by 3 | Viewed by 3884

Abstract

Spraying roads with water on a large scale in Chinese cities is one of the supplementary precaution or mitigation actions implemented to control severe air pollution events or heavy haze-fog events in which the mechanisms causing them are not yet fully understood. These [...] Read more.

Spraying roads with water on a large scale in Chinese cities is one of the supplementary precaution or mitigation actions implemented to control severe air pollution events or heavy haze-fog events in which the mechanisms causing them are not yet fully understood. These air pollution events were usually characterized by higher air humidity. Therefore, there may be a link between this action and air pollution. In the present study, the impact of water spraying on the PM_2.5 concentration and humidity in air was assessed by measuring chemical composition of the water, undertaking a simulated water spraying experiment, measuring residues and analyzing relevant data. We discovered that spraying large quantities of tap or river water on the roads leads to increased PM_2.5 concentration and humidity, and that daily continuous spraying produces a cumulative effect on air pollution. Spraying the same amount of water produces greater increases in humidity and PM_2.5 concentration during cool autumn and winter than during hot summer. Our results demonstrate that spraying roads with water increases, rather than decreases, the concentration of PM_2.5 and thus is a new source of anthropogenic aerosol and air pollution. The higher vapor content and resultant humidity most likely create unfavorable meteorological conditions for the dispersion of air pollution in autumn and winter with low temperature. Full article

(This article belongs to the Special Issue Integrated Effects of Air Pollutions and Climate Change on Human Health)

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14 pages, 1381 KiB

Open AccessFeature PaperArticle

Ocean Warming May Enhance Biochemical Alterations Induced by an Invasive Seaweed Exudate in the Mussel Mytilus galloprovincialis

by Hugo C. Vieira, Andreia C. M. Rodrigues, Sílvia F. S. Pires, Jacinta M. M. Oliveira, Rui J. M. Rocha, Amadeu M. V. M. Soares and Maria D. Bordalo

Toxics 2021, 9(6), 121; https://doi.org/10.3390/toxics9060121 - 28 May 2021

Cited by 6 | Viewed by 3765

Abstract

Ocean warming and biological invasions are among the most pervasive factors threatening coastal ecosystems with a potential to interact. Ongoing temperature rise may affect physiological and cellular mechanisms in marine organisms. Moreover, non-indigenous species spread has been a major challenge to biodiversity and [...] Read more.

Ocean warming and biological invasions are among the most pervasive factors threatening coastal ecosystems with a potential to interact. Ongoing temperature rise may affect physiological and cellular mechanisms in marine organisms. Moreover, non-indigenous species spread has been a major challenge to biodiversity and ecosystem functions and services. The invasive red seaweed Asparagopsis armata has become successfully established in Europe. Its exudate has been considered deleterious to surrounding native species, but no information exists on its effect under forecasted temperature increase. This study evaluated the combined effects of temperature rise and A. armata exudate exposure on the native mussel Mytilus galloprovincialis. Oxidative stress, neurophysiological and metabolism related biomarkers were evaluated after a 96 h-exposure to exudate (0% and 2%) under present (20 °C) and warming (24 °C) temperature scenarios. Short-term exposure to A. armata exudate affected the oxidative stress status and neurophysiology of the mussels, with a tendency to an increasing toxic action under warming. Significant oxidative damage at protein level was observed in the digestive gland and muscle of individuals exposed simultaneously to the exudate and temperature rise. Thus, under a climate change scenario, it may be expected that prolonged exposure to the combined action of both stressors may compromise M. galloprovincialis fitness and survival. Full article

(This article belongs to the Special Issue Combined Effects of Climate Change and Emerging Chemicals on Ecosystems)

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9 pages, 910 KiB

Open AccessArticle

Factors Predicting Acute Brain Injury in Cases of Carbon Monoxide Poisoning: A Prospective Registry-Based Study

by Hoon Lim, Young Hwan Lee, Sangun Nah, Sungwoo Choi, Young Soon Cho, Gi Woon Kim, Ji Eun Moon and Sangsoo Han

Toxics 2021, 9(6), 120; https://doi.org/10.3390/toxics9060120 - 27 May 2021

Cited by 2 | Viewed by 3122

Abstract

Carbon monoxide (CO) is one of the most common poisoning substances worldwide. Since acute brain injury (ABI) is an important determinant of the neurological outcome in CO poisoning, screening for patients at a high risk of developing ABI is essential for the proper [...] Read more.

Carbon monoxide (CO) is one of the most common poisoning substances worldwide. Since acute brain injury (ABI) is an important determinant of the neurological outcome in CO poisoning, screening for patients at a high risk of developing ABI is essential for the proper treatment. This study identified predictors of ABI in patients with CO poisoning. This prospective registry-based study was conducted in patients who visited a tertiary care hospital for CO poisoning from August 2016 to June 2020. ABI was defined as the presence of acute hypoxic lesions on diffusion-weighted magnetic resonance imaging. Multiple logistic regression analysis was performed to identify the predictors of ABI. Of 231 patients, 64 (27.7%) showed ABI. Multiple logistic regression analysis showed that a Glasgow Coma Scale (GCS) score <9 at presentation (odds ratio [OR] 3.28, 95% confidence interval (CI) 1.08–10.01), creatinine level >1.2 mg/dL (OR 3.04, 95% CI 1.16–8.01), and C-reactive protein (CRP) level >9.2 mg/L (OR 4.38, 95% CI 1.41–13.65) predicted ABI in cases of acute CO poisoning. In CO poisoning, the GCS score at presentation, and serum creatinine and CRP levels, were useful predictors of ABI, and may help clinicians identify high-risk patients for whom treatment should be prioritized. Full article

(This article belongs to the Special Issue Toxic Neuropathy: Mechanisms, Causes, Risk Exposure, Diagnosis, Prevention and Therapeutic Options)

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22 pages, 5178 KiB

Open AccessArticle

Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques

by Muhammad Kamil, Arifa Fatima, Sami Ullah, Gowhar Ali, Rasool Khan, Naila Ismail, Mughal Qayum, Marius Irimie, Catalina Georgeta Dinu, Hanadi Talal Ahmedah and Maria Elena Cocuz

Toxics 2021, 9(6), 119; https://doi.org/10.3390/toxics9060119 - 25 May 2021

Cited by 5 | Viewed by 3127

Abstract

Toxicity studies were conducted to provide safety data of potential drug candidates by determining lethal and toxic doses. This study was designed for pre-clinical evaluation of novel cyclohexenone derivative with respect to the acute and sub-acute toxicity along with the diabetogenic potential. Acute [...] Read more.

Toxicity studies were conducted to provide safety data of potential drug candidates by determining lethal and toxic doses. This study was designed for pre-clinical evaluation of novel cyclohexenone derivative with respect to the acute and sub-acute toxicity along with the diabetogenic potential. Acute and sub-acute toxicity were assessed after intraperitoneal (i.p) injection of the investigational compound through selected doses for 21 days. This was followed by assessment of isolated body organs (liver, kidney, heart and pancreas) via biochemical indicators and histopathological techniques. No signs of toxicity were revealed in the study of acute toxicity. Similarly, a sub-acute toxicity study showed no significant difference in biochemical indicators on 11th and 21st days between treated and control groups. However, in blood urea nitrogen (BUN) and random blood glucose/sugar (RBS) values, significant differences were recorded. Histopathological evaluation of liver, kidney, pancreas and heart tissues revealed mild to severe changes in the form of steatosis, inflammation, fibrosis, necrosis and myofibrillary damages on 11th and 21st days of treatment. In conclusion, the median lethal dose of the tested compound was expected to be greater than 500 mg/kg. No significant change occurred in selected biomarkers, except BUN and RBS levels, but a histopathological study showed moderate toxic effect on liver, kidney, pancreas and heart tissues by the cyclohexenone derivative. Full article

(This article belongs to the Section Toxicology)

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14 pages, 3267 KiB

Open AccessFeature PaperArticle

Pharmacological Modulation of Serotonin Levels in Zebrafish Larvae: Lessons for Identifying Environmental Neurotoxicants Targeting the Serotonergic System

by Melissa Faria, Eva Prats, Marina Bellot, Cristian Gomez-Canela and Demetrio Raldúa

Toxics 2021, 9(6), 118; https://doi.org/10.3390/toxics9060118 - 25 May 2021

Cited by 18 | Viewed by 3715

Abstract

This study examines the effects of acute pharmacological modulation of the serotonergic system over zebrafish larvae’s cognitive, basic, and defense locomotor behaviors, using a medium to high throughput screening assay. Furthermore, the relationship between behavior, enzyme activity related to neurotransmitter metabolism, neurotransmitter levels, [...] Read more.

This study examines the effects of acute pharmacological modulation of the serotonergic system over zebrafish larvae’s cognitive, basic, and defense locomotor behaviors, using a medium to high throughput screening assay. Furthermore, the relationship between behavior, enzyme activity related to neurotransmitter metabolism, neurotransmitter levels, and gene expression was also determined. Modulation of larvae serotonergic system was accomplished by 24 h exposure to single and opposite pharmacodynamics co-exposure to three model psychopharmaceuticals with antagonistic and agonistic serotonin signaling properties: 2.5 mM 4-Chloro-DL-phenylalanine (PCPA) and 5 µM deprenyl and 0.5 µM fluoxetine, respectively. Similar behavioral outcome was observed for deprenyl and fluoxetine, which was reflected as hypolocomotion, decrease in larvae defensive responses, and cognitive impairment. Contrarily, PCPA induced hyperlocomotion and increase in larvae escape response. Deprenyl exposure effects were more pronounced at a lower level of organization than fluoxetine, with complete inhibition of monoamine oxidase (MAO) activity, dramatic increase of 5-HT and dopamine (DA) levels, and downregulation of serotonin synthesis and transporter genes. PCPA showed mainly effects over serotonin and dopamine’s main degradation metabolites. Finally, co-exposure between agonistic and antagonist serotonin signaling drugs reviled full recovery of zebrafish impaired locomotor and defense responses, 5-HT synthesis gene expression, and partial recovery of 5-HT levels. The findings of this study suggest that zebrafish larvae can be highly sensitive and a useful vertebrate model for short-term exposure to serotonin signaling changes. Full article

(This article belongs to the Special Issue Behavioral Impairment in Aquatic Organisms Exposed to Neurotoxic Pollutants)

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13 pages, 1778 KiB

Open AccessArticle

Effects of Acrylamide-Induced Vasorelaxation and Neuromuscular Blockage: A Rodent Study

by Wei-De Lin, Chu-Chyn Ou, Shih-Hao Hsiao, Chih-Han Chang, Fuu-Jen Tsai, Jiunn-Wang Liao and Yng-Tay Chen

Toxics 2021, 9(6), 117; https://doi.org/10.3390/toxics9060117 - 24 May 2021

Cited by 2 | Viewed by 2619

Abstract

Acrylamide (ACR), which is formed during the Maillard reaction, is used in various industrial processes. ACR accumulation in humans and laboratory animals results in genotoxicity, carcinogenicity, neurotoxicity, and reproductive toxicity. In this study, we investigated the mechanisms by which ACR may induce vasorelaxation [...] Read more.

Acrylamide (ACR), which is formed during the Maillard reaction, is used in various industrial processes. ACR accumulation in humans and laboratory animals results in genotoxicity, carcinogenicity, neurotoxicity, and reproductive toxicity. In this study, we investigated the mechanisms by which ACR may induce vasorelaxation and neuromuscular toxicity. Vasorelaxation was studied using an isolated rat aortic ring model. The aortic rings were divided into the following groups: with or without endothelium, with nitric oxide synthase (NOS) inhibition, with acetylcholine receptor inhibition, and with extracellular calcium inhibition. Changes in tension were used to indicate vasorelaxation. Neuromuscular toxicity was assessed using a phrenic nerve–diaphragm model. Changes in muscle contraction stimulated by the phrenic nerve were used to indicate neuromuscular toxicity. ACR induced the vasorelaxation of phenylephrine-precontracted aortic rings, which could be significantly attenuated by NOS inhibitors. The results of the phrenic nerve–diaphragm experiments revealed that ACR reduced muscle stimulation and contraction through nicotinic acetylcholine receptor (AChR). ACR-induced vasotoxicity was regulated by NOS through the aortic endothelium. Nicotinic AChR regulated ACR-induced neuromuscular blockage. Full article

(This article belongs to the Special Issue Dietary Acrylamide: An Update on Exposure and the In Vitro and Epidemiological Evidence of Health Risks)

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11 pages, 1785 KiB

Open AccessFeature PaperArticle

Differential Modulation of the Central and Peripheral Monoaminergic Neurochemicals by Deprenyl in Zebrafish Larvae

by Marina Bellot, Helena Bartolomé, Melissa Faria, Cristian Gómez-Canela and Demetrio Raldúa

Toxics 2021, 9(6), 116; https://doi.org/10.3390/toxics9060116 - 23 May 2021

Cited by 9 | Viewed by 2859

Abstract

Zebrafish embryos and larvae are vertebrate models increasingly used in translational neuroscience research. Behavioral impairment induced by the exposure to neuroactive or neurotoxic compounds is commonly linked to changes in modulatory neurotransmitters in the brain. Although different analytical methods for determining monoaminergic neurochemicals [...] Read more.

Zebrafish embryos and larvae are vertebrate models increasingly used in translational neuroscience research. Behavioral impairment induced by the exposure to neuroactive or neurotoxic compounds is commonly linked to changes in modulatory neurotransmitters in the brain. Although different analytical methods for determining monoaminergic neurochemicals in zebrafish larvae have been developed, these methods have been used only on whole larvae, as the dissection of the brain of hundreds of larvae is not feasible. This raises a key question: Are the changes in the monoaminergic profile of the whole larvae predictive of the changes in the brain? In this study, the levels of ten monoaminergic neurotransmitters were determined in the head, trunk, and the whole body of zebrafish larvae in a control group and in those treated for 24 h with 5 M deprenyl, a prototypic monoamine-oxidase B inhibitor, eight days post-fertilization. In control larvae, most of the monoaminergic neurochemicals were found at higher levels in the head than in the trunk. Significant changes were found in the distribution of some neurochemicals after deprenyl-treatment, with serotonin and norepinephrine increasing in both the head and the trunk, whereas dopamine, L-DOPA, and homovanillic acid levels were only modulated in the head. In fact, the highly significant increase in dopamine levels observed in the head after deprenyl-treatment was not detected in the whole-body analysis. These results indicate that the analysis of neurotransmitters in the zebrafish larvae whole-body should not be used as a general surrogate of the brain. Full article

(This article belongs to the Special Issue Fish Models for Human Toxicology)

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15 pages, 1018 KiB

Open AccessFeature PaperArticle

Evaluation of the Potential of Sewage Sludge Mycobiome to Degrade High Diclofenac and Bisphenol-A Concentrations

by Ulises Conejo-Saucedo, Alejandro Ledezma-Villanueva, Gabriela Ángeles de Paz, Mario Herrero-Cervera, Concepción Calvo and Elisabet Aranda

Toxics 2021, 9(6), 115; https://doi.org/10.3390/toxics9060115 - 23 May 2021

Cited by 13 | Viewed by 3563

Abstract

One of the most challenging environmental threats of the last two decades is the effects of emerging pollutants (EPs) such as pharmaceutical compounds or industrial additives. Diclofenac and bisphenol A have regularly been found in wastewater treatment plants, and in soils and water [...] Read more.

One of the most challenging environmental threats of the last two decades is the effects of emerging pollutants (EPs) such as pharmaceutical compounds or industrial additives. Diclofenac and bisphenol A have regularly been found in wastewater treatment plants, and in soils and water bodies because of their extensive usage and their recalcitrant nature. Due to the fact of this adversity, fungal communities play an important role in being able to safely degrade EPs. In this work, we obtained a sewage sludge sample to study both the culturable and non-culturable microorganisms through DNA extraction and massive sequencing using Illumina MiSeq techniques, with the goal of finding degraders adapted to polluted environments. Afterward, degradation experiments on diclofenac and bisphenol A were performed with the best fungal degraders. The analysis of bacterial diversity showed that Dethiosulfovibrionaceae, Comamonadaceae, and Isosphaeraceae were the most abundant families. A predominance of Ascomycota fungi in the culturable and non-culturable population was also detected. Species such as Talaromyces gossypii, Syncephalastrum monosporum, Aspergillus tabacinus, and Talaromyces verruculosus had remarkable degradation rates, up to 80% of diclofenac and bisphenol A was fully degraded. These results highlight the importance of characterizing autochthonous microorganisms and the possibility of selecting native fungal microorganisms to develop tailored biotransformation technologies for EPs. Full article

(This article belongs to the Special Issue Advanced Technologies to Remove Toxic Compounds in Wastewater)

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