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14 pages, 4897 KiB

Open AccessArticle

A Phenotypic and Genotypic Evaluation of Developmental Toxicity of Polyhexamethylene Guanidine Phosphate Using Zebrafish Embryo/Larvae

by Jeongah Song, Kojo Eghan, Sangwoo Lee, Jong-Su Park, Seokjoo Yoon, Wittaya Pimtong and Woo-Keun Kim

Toxics 2020, 8(2), 33; https://doi.org/10.3390/toxics8020033 - 2 May 2020

Cited by 3 | Viewed by 4712

Abstract

Polyhexamethylene guanidine-phosphate (PHMG-P), a guanidine-based cationic antimicrobial polymer, is an effective antimicrobial biocide, potent even at low concentrations. Due to its resilient bactericidal properties, it has been used extensively in consumer products. It was safely used until its use in humidifiers led to [...] Read more.

Polyhexamethylene guanidine-phosphate (PHMG-P), a guanidine-based cationic antimicrobial polymer, is an effective antimicrobial biocide, potent even at low concentrations. Due to its resilient bactericidal properties, it has been used extensively in consumer products. It was safely used until its use in humidifiers led to a catastrophic event in South Korea. Epidemiological studies have linked the use of PHMG-P as a humidifier disinfectant to pulmonary fibrosis. However, little is known about its harmful impacts other than pulmonary fibrosis. Thus, we applied a zebrafish embryo/larvae model to evaluate developmental and cardiotoxic effects and transcriptome changes using RNA-sequencing. Zebrafish embryos were exposed to 0.1, 0.2, 0.3, 0.4, 0.5, 1, and 2 mg/L of PHMG-P from 3 h to 96 h post fertilization. 2 mg/L of PHMG-P resulted in total mortality and an LC₅₀ value at 96 h was determined at 1.18 mg/L. Significant developmental changes were not observed but the heart rate of zebrafish larvae was significantly altered. In transcriptome analysis, immune and inflammatory responses were significantly affected similarly to those in epidemiological studies. Our qPCR analysis (Itgb1b, TNC, Arg1, Arg2, IL-1β, Serpine-1, and Ptgs2b) also confirmed this following a 96 h exposure to 0.4 mg/L of PHMG-P. Based on our results, PHMG-P might induce lethal and cardiotoxic effects in zebrafish, and crucial transcriptome changes were linked to immune and inflammatory response. Full article

(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)

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8 pages, 1907 KiB

Open AccessCommunication

New Insights into the Toxicokinetics of 3,4-Dichloroaniline in Early Life Stages of Zebrafish (Danio rerio)

by Sabrina Schiwy, Ann-Kathrin Herber, Henner Hollert and Markus Brinkmann

Toxics 2020, 8(1), 16; https://doi.org/10.3390/toxics8010016 - 1 Mar 2020

Cited by 12 | Viewed by 3653

Abstract

In the fish embryo toxicity (FET) test with zebrafish (Danio rerio) embryos, 3,4-dichloroaniline (3,4-DCA) is often employed as a positive control substance. Previous studies have characterized bioconcentration and transformation of 3,4-DCA in this test under flow-through conditions. However, the dynamic changes [...] Read more.

In the fish embryo toxicity (FET) test with zebrafish (Danio rerio) embryos, 3,4-dichloroaniline (3,4-DCA) is often employed as a positive control substance. Previous studies have characterized bioconcentration and transformation of 3,4-DCA in this test under flow-through conditions. However, the dynamic changes of chemical concentrations in exposure media and embryos were not studied systematically under the commonly used semi-static exposure conditions in multiwell plates. To overcome these limitations, we conducted semi-static exposures experiments where embryolarval zebrafish were exposed to 0.5, 2.0, and 4.0 mg L⁻¹ of 3,4-DCA for up to 120 hpf, with 24-h renewal intervals. During each renewal interval, concentrations of 3,4-DCA were quantified in water samples at 0, 6, 18, and 24 h using high-performance liquid chromatography with diode array detection. Levels of 3,4-DCA in larvae were measured after 120 h exposure. Concentrations of 3,4-DCA in the test vessels decreased rapidly during exposure. Taking these dynamics into account, bioconcentration factors in the present study ranged from 12.9 to 29.8 L kg⁻¹, depending on exposure concentration. In summary, this study contributed to our knowledge of chemical dynamics in the FET test with embryolarval zebrafish, which will aid in defining suitable exposure conditions for future studies. Full article

(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)

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14 pages, 5394 KiB

Open AccessArticle

Toxic Effects of Paclobutrazol on Developing Organs at Different Exposure Times in Zebrafish

by Wen-Der Wang, Chang-Yi Wu and Bonick Kartini Lonameo

Toxics 2019, 7(4), 62; https://doi.org/10.3390/toxics7040062 - 6 Dec 2019

Cited by 20 | Viewed by 8654

Abstract

To enhance crop productivity and economic profit, farmers often use pesticides that modulate plant growth and prevent disease. However, contamination of ecosystems with agricultural pesticides may impair the health of resident biota. Paclobutrazol (PBZ), an aromatic-containing triazole, is widely applied to many crops [...] Read more.

To enhance crop productivity and economic profit, farmers often use pesticides that modulate plant growth and prevent disease. However, contamination of ecosystems with agricultural pesticides may impair the health of resident biota. Paclobutrazol (PBZ), an aromatic-containing triazole, is widely applied to many crops in order to promote flowering and fruit setting, while also regulating plant growth and preventing fungus-related diseases. Due to its high mobility, high stability and potential for bioaccumulation, the risks of PBZ to the health of organisms and ecological systems have become a serious concern. In previous studies, we documented the toxicity of PBZ on developing heart, eyes, liver, pancreas and intestine of zebrafish. In this study, we sought to further understand the developmental stage-specific impacts of PBZ on digestive organs and other tissues. Zebrafish were exposed to PBZ beginning at different embryonic stages, and the toxic effects on organs were evaluated at 120 hpf (hours post-fertilization) by in situ hybridization staining with tissue-specific marker genes, such as liver, intestine and pancreas. Unsurprisingly, early-stage embryos exhibited higher sensitivity to PBZ-induced death and developmental hypoplasia of digestive organs. Interestingly, the developing liver and pancreas were more sensitive to PBZ than intestine when embryos were exposed at early stages, but these tissues showed lower sensitivity at later stages. Our delineation of the differential toxic effects of PBZ on developing organs at different exposure timings can serve as a powerful reference for further studies into the mechanisms of PBZ organ toxicity. Full article

(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)

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21 pages, 3101 KiB

Open AccessArticle

Exposure of Larval Zebrafish to the Insecticide Propoxur Induced Developmental Delays that Correlate with Behavioral Abnormalities and Altered Expression of hspb9 and hspb11

by Jeremiah N. Shields, Eric C. Hales, Lillian E. Ranspach, Xixia Luo, Steven Orr, Donna Runft, Alan Dombkowski, Melody N. Neely, Larry H. Matherly, Jeffrey W. Taub, Tracie R. Baker and Ryan Thummel

Toxics 2019, 7(4), 50; https://doi.org/10.3390/toxics7040050 - 21 Sep 2019

Cited by 6 | Viewed by 4838

Abstract

Recent studies suggest that organophosphates and carbamates affect human fetal development, resulting in neurological and growth impairment. However, these studies are conflicting and the extent of adverse effects due to pesticide exposure warrants further investigation. In the present study, we examined the impact [...] Read more.

Recent studies suggest that organophosphates and carbamates affect human fetal development, resulting in neurological and growth impairment. However, these studies are conflicting and the extent of adverse effects due to pesticide exposure warrants further investigation. In the present study, we examined the impact of the carbamate insecticide propoxur on zebrafish development. We found that propoxur exposure delays embryonic development, resulting in three distinct developmental stages: no delay, mild delay, or severe delay. Interestingly, the delayed embryos all physically recovered 5 days after exposure, but behavioral analysis revealed persistent cognitive deficits at later stages. Microarray analysis identified 59 genes significantly changed by propoxur treatment, and Ingenuity Pathway Analysis revealed that these genes are involved in cancer, organismal abnormalities, neurological disease, and hematological system development. We further examined hspb9 and hspb11 due to their potential roles in zebrafish development and found that propoxur increases expression of these small heat shock proteins in all of the exposed animals. However, we discovered that less significant increases were associated with the more severely delayed phenotype. This raises the possibility that a decreased ability to upregulate these small heat shock proteins in response to propoxur exposure may cause embryos to be more severely delayed. Full article

(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)

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17 pages, 2636 KiB

Open AccessArticle

Toxicity of Aqueous L-Selenomethionine and Tert-Butyl Hydroperoxide Exposure to Zebrafish (Danio rerio) Embryos Following Tert-Butyl Hydroquinone Treatment

by Allyson K. Gerhart and David M. Janz

Toxics 2019, 7(3), 44; https://doi.org/10.3390/toxics7030044 - 29 Aug 2019

Cited by 4 | Viewed by 4469

Abstract

Aqueous L-selenomethionine (SeMet) embryo exposures represent a rapid and simplified method for investigating the embryotoxic effects of SeMet. Using zebrafish (Danio rerio) as a model organism, the objective of the present study was to characterize the effects of waterborne exposure to [...] Read more.

Aqueous L-selenomethionine (SeMet) embryo exposures represent a rapid and simplified method for investigating the embryotoxic effects of SeMet. Using zebrafish (Danio rerio) as a model organism, the objective of the present study was to characterize the effects of waterborne exposure to both SeMet and tert-butyl hydroperoxide (tBOOH) to early life stages of zebrafish pre-treated with the antioxidant tert-butyl hydroquinone (tBHQ) in an attempt to investigate the mechanism of Se toxicity as it relates to oxidative stress. During the initial concentration range finding experiment, recently fertilized embryos were exposed for five days to 5, 25, 125, and 625 µg Se/L (as SeMet). These exposures informed the second experiment in which embryos were exposed to two concentrations of SeMet (25 and 125 µg Se/L) and 75 mg/L tBOOH either with (tBOOH-t, 25-t, 125-t) or without (tBOOH, 25, 125) a 4 h 100 µg/L tBHQ pre-treatment. Survival, hatchability, time to hatch, the frequency and severity of deformities (total and type), and changes in the expression of seven antioxidant-associated genes were determined. Exposures to SeMet and tBOOH reduced hatchability, increased time to hatch, decreased survival, increased the incidence and severity of deformities, and increased glutathione-disulfide reductase (gsr) expression in the pre-treated tBOOH treatment group. Full article

(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)

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23 pages, 3909 KiB

Open AccessArticle

Health Impact Assessment of Sulfolane on Embryonic Development of Zebrafish (Danio rerio)

by Soham M. Shah, Michael Wahba, Linlong Yu, Gopal Achari and Hamid R. Habibi

Toxics 2019, 7(3), 42; https://doi.org/10.3390/toxics7030042 - 23 Aug 2019

Cited by 15 | Viewed by 4540

Abstract

Sulfolane is a widely used polar, aprotic solvent that has been detected by chemical analysis in groundwater and creeks around the world including Alberta, Canada (800 µg/mL), Louisiana, USA (2900 µg/mL) and Brisbane, Australia (4344 µg/mL). Previous research provided information on adverse effects [...] Read more.

Sulfolane is a widely used polar, aprotic solvent that has been detected by chemical analysis in groundwater and creeks around the world including Alberta, Canada (800 µg/mL), Louisiana, USA (2900 µg/mL) and Brisbane, Australia (4344 µg/mL). Previous research provided information on adverse effects of sulfolane on mammals, but relatively little information is available on aquatic organisms. This study tested the effects of sulfolane (0–5000 µg/mL) on early development of zebrafish larvae, using various morphometric (survival, hatching, yolk sac and pericardial oedema, haemorrhaging, spinal malformations, swim bladder inflation), growth (larval length, eye volume, yolk sac utilisation), behavioural (touch response, locomotor activity and transcript abundance parameters (ahr1a, cyp1a, thraa, dio1, dio2, dio3, 11βhsd2, gr, aqp3a, cyp19a1b, ddc, gria2b and hsp70) for 120 h. Embryos were chronically exposed to sulfolane throughout the experimental period. For locomotor activity, however, we also investigated acute response to 2-h sulfolane treatment. Sulfolane sensitivity causing significant impairment in the observed parameters were different depending on parameters measured, including survival (concentrations greater than 800 µg/mL), morphometric and growth (800–1000 µg/mL), behaviour (500–800 µg/mL) and transcript abundance (10 µg/mL). The overall results provide novel information on the adverse health impacts of sulfolane on an aquatic vertebrate species, and an insight into developmental impairments following exposure to environmental levels of sulfolane in fish embryos. Full article

(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)

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10 pages, 1890 KiB

Open AccessArticle

Cytotoxicity and Toxicity Evaluation of Xanthone Crude Extract on Hypoxic Human Hepatocellular Carcinoma and Zebrafish (Danio rerio) Embryos

by Shazrul Fazry, Muhammad Akram Mohd Noordin, Salahuddin Sanusi, Mahanem Mat Noor, Wan Mohd Aizat, Azwan Mat Lazim, Herryawan Ryadi Eziwar Dyari, Nur Hidayah Jamar, Juwairiah Remali, Babul Airianah Othman, Douglas Law, Nik Marzuki Sidik, Yew Hoong Cheah and Yi Chieh Lim

Toxics 2018, 6(4), 60; https://doi.org/10.3390/toxics6040060 - 9 Oct 2018

Cited by 15 | Viewed by 4463

Abstract

Xanthone is an organic compound mostly found in mangosteen pericarp and widely known for its anti-proliferating effect on cancer cells. In this study, we evaluated the effects of xanthone crude extract (XCE) and α-mangostin (α-MG) on normoxic and hypoxic human hepatocellular carcinoma (HepG2) [...] Read more.

Xanthone is an organic compound mostly found in mangosteen pericarp and widely known for its anti-proliferating effect on cancer cells. In this study, we evaluated the effects of xanthone crude extract (XCE) and α-mangostin (α-MG) on normoxic and hypoxic human hepatocellular carcinoma (HepG2) cells and their toxicity towards zebrafish embryos. XCE was isolated using a mixture of acetone and water (80:20) and verified via high performance liquid chromatography (HPLC). Both XCE and α-MG showed higher anti-proliferation effects on normoxic HepG2 cells compared to the control drug, 5-fluorouracil (IC₅₀ = 50.23 ± 1.38, 8.39 ± 0.14, and 143.75 ± 15.31 μg/mL, respectively). In hypoxic conditions, HepG2 cells were two times less sensitive towards XCE compared to normoxic HepG2 cells (IC₅₀ = 109.38 ± 1.80 μg/mL) and three times less sensitive when treated with >500 μg/mL 5-fluorouracil (5-FU). A similar trend was seen with the α-MG treatment on hypoxic HepG2 cells (IC₅₀ = 10.11 ± 0.05 μg/mL) compared to normoxic HepG2 cells. However, at a concentration of 12.5 μg/mL, the α-MG treatment caused tail-bend deformities in surviving zebrafish embryos, while no malformation was observed when embryos were exposed to XCE and 5-FU treatments. Our study suggests that both XCE and α-MG are capable of inhibiting HepG2 cell proliferation during normoxic and hypoxic conditions, more effectively than 5-FU. However, XCE is the preferred option as no malformation was observed in surviving zebrafish embryos and it is more cost efficient than α-MG. Full article

(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)

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Review

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12 pages, 237 KiB

Open AccessReview

Dietary Contaminants and Their Effects on Zebrafish Embryos

by Marc Tye and Mark A. Masino

Toxics 2019, 7(3), 46; https://doi.org/10.3390/toxics7030046 - 7 Sep 2019

Cited by 7 | Viewed by 4139

Abstract

Dietary contaminants are often an over-looked factor in the health of zebrafish. Typically, water is considered to be the source for most contaminants, especially within an aquatic environment. For this reason, source water for zebrafish recirculating systems is highly regulated and monitored daily. [...] Read more.

Dietary contaminants are often an over-looked factor in the health of zebrafish. Typically, water is considered to be the source for most contaminants, especially within an aquatic environment. For this reason, source water for zebrafish recirculating systems is highly regulated and monitored daily. Most facilities use reverse osmosis or de-ionized water filtration systems to purify incoming water to ensure that contaminants, as well as pathogens, do not enter their zebrafish housing units. However, diets are rarely tested for contaminants and, in the case of manufactured zebrafish feeds, since the product is marketed for aquaculture or aquarium use it is assumed that the feed is acceptable for animals used for research. The following provides examples as to how contaminants could lead to negative effects on development and behavior of developing zebrafish. Full article

(This article belongs to the Special Issue Contaminant Effects on Zebrafish Embryos)

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