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Toxics
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Drug Metabolism and Toxicological Mechanisms
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Drug Metabolism and Toxicological Mechanisms

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 17534

Special Issue Editors

Prof. Dr. Qi Wang

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Guest Editor
Department of Toxicology, Peking University, Beijing, China
Interests: cellular and computational toxicology
Dr. Youbo Zhang

E-Mail Website
Guest Editor
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Interests: natural products analysis; pharmacological research; nuclear receptor function; metabolic diseases
Special Issues, Collections and Topics in MDPI journals
Dr. An Zhu

E-Mail Website
Guest Editor
Research Centre of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
Interests: drug toxicology; computational toxicology; epitranscriptomics

Special Issue Information

Dear Colleagues,

Absorption, distribution, metabolism, and excretion (ADME) processes are of importance in understanding how the body disposes and responds to drugs. These processes play a pivotal role in assessing the efficacy and safety of drugs, while also enabling the prediction of potential adverse reactions or toxicities. A parent drug can undergo biotransformation by drug-metabolizing enzymes, leading to the formation of either toxic metabolites (metabolic activation) or non-toxic metabolites (detoxification). Thus, drug metabolism can be a key determinant of drug toxicity. Recently, new approach methodologies such as in silico methods, based on non-animal data, have been developed and applied in regulatory practices.

This Special Issue mainly focuses on drug metabolism and toxicological mechanisms. It extensively covers a range of topics, including drug metabolism, physiologically based pharmacokinetic (PBK) modeling, toxicokinetics–toxicodynamics (TK–TD), ADME characterization, the identification and toxicity of metabolites, high-throughput pharmacokinetics (HT-PK), organ-specific toxicity, and toxicological mechanisms.

Prof. Dr. Qi Wang
Dr. Youbo Zhang
Dr. An Zhu
Guest Editors

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Keywords

  • drug metabolism
  • toxicity
  • mechanism
  • preclinical study
  • clinical trial

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Published Papers (11 papers)

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11 pages, 209 KiB  
Article
Ethephon Poisoning: Clinical Characteristics and Outcomes
by Satariya Trakulsrichai, Kanokrat Chuayaupakarn, Phantakan Tansuwannarat, Panee Rittilert, Achara Tongpoo, Charuwan Sriapha and Winai Wananukul
Toxics 2025, 13(2), 115; https://doi.org/10.3390/toxics13020115 - 31 Jan 2025
Viewed by 383
Abstract
Ethephon (2-chloroethylphosphonic acid) is a generally used plant growth regulator, but the data on its toxic effects, especially in humans, are very limited. This study was conducted to describe the clinical characteristics, management, and outcomes of patients exposed to products containing ethephon. We [...] Read more.
Ethephon (2-chloroethylphosphonic acid) is a generally used plant growth regulator, but the data on its toxic effects, especially in humans, are very limited. This study was conducted to describe the clinical characteristics, management, and outcomes of patients exposed to products containing ethephon. We performed an 8-year retrospective study using data from the Ramathibodi Poison Center database (2013–2020), which included 252 patients. Most patients were male, with a median age of 32 years. Almost all patients were exposed through ingestion, mainly in unintentional circumstances. The clinical presentations included local effects, gastrointestinal (GI), neurological, and respiratory symptoms. Some patients required hospital admission; specifically, seven patients received inotropic drugs, and six were intubated with ventilator support. Most patients had either no or only minor clinical effects. However, six patients experienced moderate/severe effects, and two patients died. Age, intentional exposure, and the presence of initial neurological symptoms could prognosticate moderate to fatal outcomes. In conclusion, exposure to ethephon predominantly resulted in no or minor effects, and GI symptoms were the most common clinical manifestation. The cholinergic toxic syndrome was not frequently observed. The mortality rate was very low. Patients presenting with factors associated with worse outcomes should be monitored closely for clinical deterioration and appropriately managed. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
15 pages, 3568 KiB  
Article
Bisphenol S Induces Lipid Metabolism Disorders in HepG2 and SK-Hep-1 Cells via Oxidative Stress
by Kai-Xing Lin, Zi-Yao Wu, Mei-Lin Qin and Huai-Cai Zeng
Toxics 2025, 13(1), 44; https://doi.org/10.3390/toxics13010044 - 8 Jan 2025
Viewed by 579
Abstract
Bisphenol S (BPS) is a typical endocrine disruptor associated with obesity. To observe BPS effects on lipid metabolism in HepG2 and SK-Hep-1 human HCC cells, a CCK-8 assay was used to assess cell proliferation in response to BPS, and the optimal concentration of [...] Read more.
Bisphenol S (BPS) is a typical endocrine disruptor associated with obesity. To observe BPS effects on lipid metabolism in HepG2 and SK-Hep-1 human HCC cells, a CCK-8 assay was used to assess cell proliferation in response to BPS, and the optimal concentration of BPS was selected. Biochemical indices such as triglyceride (TG) and total cholesterol (T-CHO), and oxidative stress indices such as malondialdehyde (MDA) and catalase (CAT) were measured. ROS and MDA levels were significantly increased after BPS treatment for 24 h and 48 h (p < 0.05), indicating an oxidative stress response. Alanine aminotransferase (ALT), T-CHO, and low-density lipoprotein cholesterol (LDL-C) levels also increased significantly after 24 or 48 h BPS treatments (p < 0.05). RT-PCR and Western blot analyses detected mRNA or protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein 1c (SREBP1C). The results indicated that BPS could inhibit the mRNA expression of PPARα and carnitine palmitoyl transferase 1B (CPT1B), reduce lipid metabolism, promote mRNA or protein expression of SREBP1C and fatty acid synthase (FASN), and increase lipid synthesis. Increased lipid droplets were observed using morphological Oil Red O staining. Our study demonstrates that BPS may cause lipid accumulation by increasing oxidative stress and perturbing cellular lipid metabolism. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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23 pages, 4606 KiB  
Article
Modulation of Paracetamol-Induced Hepatotoxicity by Acute and Chronic Ethanol Consumption in Mice: A Study Pilot
by Allan Cristian Gonçalves, Aline Meireles Coelho, Maria Laura da Cruz Castro, Renata Rebeca Pereira, Natalia Pereira da Silva Araújo, Flávia Monteiro Ferreira, Pedro Alves Machado Júnior, Sirlaine Pio, Camilo Elber Vital, Frank Silva Bezerra, André Talvani, William de Castro Borges, Emerson Cruz de Oliveira and Daniela Caldeira Costa
Toxics 2024, 12(12), 857; https://doi.org/10.3390/toxics12120857 - 27 Nov 2024
Viewed by 1130
Abstract
Paracetamol (APAP) overdose is the leading cause of drug-induced liver injury, leading to acute liver failure. However, the role of concurrent acute or chronic ethanol ingestion in this context requires further clarification. In this study, we investigated the effects of acute and chronic [...] Read more.
Paracetamol (APAP) overdose is the leading cause of drug-induced liver injury, leading to acute liver failure. However, the role of concurrent acute or chronic ethanol ingestion in this context requires further clarification. In this study, we investigated the effects of acute and chronic ethanol ingestion on APAP-induced hepatotoxicity. Male C57BL/6 mice were randomly allocated into four groups: control (C; water 2×/day for 7 days); APAP (single dose of APAP, 500 mg/kg); acute ethanol (AE; a single ethanol dose—10 mL/kg, and one hour later an overdose of APAP—500 mg/kg); chronic ethanol (CE; ethanol—10 mL/kg, 2×/day for 7 days; and on the last day, an overdose of APAP—500 mg/kg). The results showed that AE induced heightened liver damage, increased necrotic area, and elevated levels of ALT, AST, TBARS, and oxidized glutathione compared to the control group. The AE group exhibited diminished glutathione availability and elevated CYP2E1 levels compared to the other groups. CE maintained a hepatic profile similar to that of the control group in terms of necrosis index, ALT and AST levels, GSH/GSSG ratio, and CYP2E1 activity, along with the upregulation of gene expression of the glucuronidation enzyme compared to the APAP group. Proteomic analysis revealed that the AE protein profile closely resembled that of the APAP group, whereas the C and CE groups were clustered together. In conclusion, ethanol consumption differentially modulated APAP overdose-induced liver damage. Acute consumption exacerbated hepatotoxicity, similar to an APAP overdose alone, whereas chronic consumption appeared to mitigate this injury, at least within the parameters assessed in this study. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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16 pages, 11135 KiB  
Article
The Acute Toxicity and Cardiotoxic Effects of Protocatechuic Aldehyde on Juvenile Zebrafish
by Jiufeng Yin, Hui Wang, Feng Zhao, Dan Liang, Wenqing Yang and Dan Zhang
Toxics 2024, 12(11), 799; https://doi.org/10.3390/toxics12110799 - 3 Nov 2024
Cited by 1 | Viewed by 2630
Abstract
Protocatechuic aldehyde (PCA) is a natural phenolic acid compound with pharmacological effects such as anti-oxidative stress, antibacterial, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, and anti-tumor. Despite the favorable therapeutic effects of PCA, it is imperative to recognize that adverse drug reactions can arise even with [...] Read more.
Protocatechuic aldehyde (PCA) is a natural phenolic acid compound with pharmacological effects such as anti-oxidative stress, antibacterial, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, and anti-tumor. Despite the favorable therapeutic effects of PCA, it is imperative to recognize that adverse drug reactions can arise even with satisfactory quality assurance measures and during standard clinical application and dosing. Additionally, the acute toxicity and cardiotoxic sequelae of PCA are frequently under reported in the available documentation. To investigate the acute toxicity and cardiotoxic effects of PCA, the present study comprehensively assessed the acute toxicity and cardiotoxic effects of PCA by administering different concentrations of PCA and by monitoring the phenotypic changes in zebrafish, using AB wild-type Tg(cmlc2:EGFP) zebrafish as the experimental model organism. Meanwhile, the target genes of PCA that may cause cardiotoxicity were predicted and validated using a network pharmacology approach. Our findings indicated that PCA exhibited severe acute toxicity and cardiotoxic effects in zebrafish at 70 μg/mL and 80 μg/mL. Furthermore, PIK3CA, PARP1, and GSK3β may be involved in the mechanism of action of the cardiotoxicity-inducing effects of this compound. The present investigation has afforded a deeper insight into the acute toxicity and cardiotoxic impacts of PCA on zebrafish and has established a significant theoretical foundation for the evaluation of toxicity in pharmaceuticals incorporating PCA. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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19 pages, 6688 KiB  
Article
Actin Dysregulation Mediates Nephrotoxicity of Cassiae Semen Aqueous Extracts
by Jinlan Yang, Sheng Xiao, Ludi Li, An Zhu, Wusheng Xiao and Qi Wang
Toxics 2024, 12(8), 556; https://doi.org/10.3390/toxics12080556 - 30 Jul 2024
Viewed by 1170
Abstract
Cassiae semen, commonly consumed as roasted tea, has been widely used for both medicinal purposes and dietary supplements. In this study, we investigated the nephrotoxic effects and underlying mechanisms of Cassiae semen aqueous extracts (CSAEs) using computational and animal models. Both male and [...] Read more.
Cassiae semen, commonly consumed as roasted tea, has been widely used for both medicinal purposes and dietary supplements. In this study, we investigated the nephrotoxic effects and underlying mechanisms of Cassiae semen aqueous extracts (CSAEs) using computational and animal models. Both male and female Sprague Dawley rats were treated with 4.73–47.30 g/kg (body weight) of CSAEs by oral gavage twice a day for 7–28 days. We found that serum and urinary biomarkers of kidney injury and kidney coefficients were increased in a dose-dependent manner, and were accompanied by morphological alterations in the kidneys of CSAEs-treated rats. Computational and molecular docking approaches predicted that the three most abundant components of CSAEs—obtusifolin, aurantio-obtusin, and obtusin—exhibited strong affinity for the binding of F-actin, ROCK1, and Rac1, and the RhoA–ROCK pathway was identified as the most likely regulatory mechanism mediating the nephrotoxicity of CSAEs. Consistently, immunofluorescence staining revealed F-actin and cytoskeleton were frequently disturbed in renal cells and brush borders at high doses of CSAEs. Results from gene expression analyses confirmed that CSAEs suppressed the key proteins in the RhoA–ROCK signaling pathway and consequently the expression of F-actin and its stabilization genes. In summary, our findings suggest that Cassiae semen can depolymerize and destabilize actin cytoskeleton by inhibition of the RhoA–ROCK pathway and/or direct binding to F-actin, leading to nephrotoxicity. The consumption of Cassiae semen as a supplement and medicine warrants attention. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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12 pages, 541 KiB  
Article
Risk Factors of Optic Neuropathy in Ethambutol Users: Interaction with Isoniazid and Other Associated Conditions of Toxic Optic Neuropathy
by Jiyeong Kim and Seong Joon Ahn
Toxics 2024, 12(8), 549; https://doi.org/10.3390/toxics12080549 - 30 Jul 2024
Viewed by 1276
Abstract
(1) Background: To investigate the risk factors associated with optic neuropathy (ON) and validate the hypothesis that concomitant isoniazid use and other causes of toxic ON affect the development of ON in ethambutol users. (2) Methods: This cohort study identified ethambutol users who [...] Read more.
(1) Background: To investigate the risk factors associated with optic neuropathy (ON) and validate the hypothesis that concomitant isoniazid use and other causes of toxic ON affect the development of ON in ethambutol users. (2) Methods: This cohort study identified ethambutol users who initiated ethambutol therapy between January 2015 and December 2021 and had no ON prior to ethambutol therapy. ON incidence up to 31 December 2022 was evaluated. The users were grouped on the basis of the presence of ON. Demographic and clinical characteristics were investigated for risk factor analyses of ON. Odds ratios (ORs) were calculated using multivariate logistic regression analyses. (3) Results: Among 204,598 ethambutol users, 5277 (2.6%) patients developed ON over the study period. Patients with ON included a higher percentage of women and had a higher mean age than patients without ON. In the multivariate analyses, the risk factors for ON and visual impairment included sex, age, cumulative dose, extrapulmonary indications for ethambutol use, and systemic conditions such as diabetes, hypertension, hyperlipidemia, diabetes, kidney disease, and liver disease. Malnutrition or nutritional disorders significantly increased the risk of ON (OR = 1.27, 95% confidence interval [CI] = 1.19–1.34), whereas concomitant isoniazid use decreased the risk (OR = 0.78, 95% CI = 0.72–0.86). (4) Conclusion: An increased risk of ON in patients with systemic diseases and nutritional deficiency was identified, whereas concomitant isoniazid use was associated with a decreased risk of ON. Patients with these risk factors should be carefully monitored to minimize the vision-threatening ON. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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12 pages, 2682 KiB  
Article
Rutaecarpine Aggravates Acetaminophen-Induced Acute Liver Injury by Inducing CYP1A2
by Meiqi Wan, Hua Gao, Xiaoyan Liu and Youbo Zhang
Toxics 2024, 12(7), 515; https://doi.org/10.3390/toxics12070515 - 18 Jul 2024
Viewed by 1637
Abstract
In this study, we investigated whether rutaecarpine could aggravate acetaminophen-induced acute liver damage in vivo and in vitro. CCK-8 and apoptosis assays were performed to verify the cytotoxicity of acetaminophen to L02 cells with or without rutaecarpine. The expression levels of the target [...] Read more.
In this study, we investigated whether rutaecarpine could aggravate acetaminophen-induced acute liver damage in vivo and in vitro. CCK-8 and apoptosis assays were performed to verify the cytotoxicity of acetaminophen to L02 cells with or without rutaecarpine. The expression levels of the target proteins and genes were determined using Western blotting and qRT-PCR. The liver pathological changes were evaluated with hematoxylin and eosin staining, while the aspartate aminotransferase (AST) and alanine aminotransferase (AST) levels in plasma were measured to assess the liver damage. Our results revealed that pretreatment of the cell and mice with rutaecarpine significantly aggravated the acetaminophen-induced liver damage. Mechanistically, rutaecarpine induces the CYP1A2 protein, which accelerates the metabolism of acetaminophen to produce a toxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI), leading to severe liver inflammation. Rutaecarpine exacerbated the liver damage by upregulating CYP1A2 and proinflammatory factors. These findings highlight the importance of carefully considering the dosage of rutaecarpine when combined with acetaminophen in drug design and preclinical trials. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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19 pages, 7555 KiB  
Article
Ribosomal Dysregulation in Metastatic Laryngeal Squamous Cell Carcinoma: Proteomic Insights and CX-5461’s Therapeutic Promise
by Miao Gao, Ting Liu, Kairui Hu, Songling Chen, Shixin Wang, Di Gan, Zhihan Li and Xiaohuang Lin
Toxics 2024, 12(5), 363; https://doi.org/10.3390/toxics12050363 - 13 May 2024
Cited by 1 | Viewed by 1979
Abstract
One of the main barriers to the successful treatment of laryngeal squamous cell carcinoma (LSCC) is postoperative progression, primarily due to tumor cell metastasis. To systematically investigate the molecular characteristics and potential mechanisms underlying the metastasis in laryngeal cancer, we carried out a [...] Read more.
One of the main barriers to the successful treatment of laryngeal squamous cell carcinoma (LSCC) is postoperative progression, primarily due to tumor cell metastasis. To systematically investigate the molecular characteristics and potential mechanisms underlying the metastasis in laryngeal cancer, we carried out a TMT-based proteomic analysis of both cancerous and adjacent non-cancerous tissues from 10 LSCC patients with lymph node metastasis (LNM) and 10 without. A total of 5545 proteins were quantified across all samples. We identified 57 proteins that were downregulated in LSCC with LNM, which were enriched in cell adhesion pathways, and 69 upregulated proteins predominantly enriched in protein production pathways. Importantly, our data revealed a strong correlation between increased ribosomal activity and the presence of LNM, as 18 ribosomal subunit proteins were found to be upregulated, with RPS10 and RPL24 being the most significantly overexpressed. The potential of ribosomal proteins, including RPS10 and RPL24, as biomarkers for LSCC with LNM was confirmed in external validation samples (six with LNM and six without LNM) using Western blotting and immunohistochemistry. Furthermore, we have confirmed that the RNA polymerase I inhibitor CX-5461, which impedes ribosome biogenesis in LSCC, also decreases the expression of RPS10, RPL24, and RPS26. In vitro experiments have revealed that CX-5461 moderately reduces cell viability, while it significantly inhibits the invasion and migration of LSCC cells. It can enhance the expression of the epithelial marker CDH1 and suppress the expression of the mesenchymal markers CDH2, VIM, and FN at a dose that does not affect cell viability. Our study broadens the scope of the proteomic data on laryngeal cancer and suggests that ribosome targeting could be a supplementary therapeutic strategy for metastatic LSCC. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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25 pages, 8842 KiB  
Article
Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/β-Catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity
by Qibin Wu, Xinyue Gao, Yifan Lin, Caijin Wu, Jian Zhang, Mengting Chen, Jiaxin Wen, Yajiao Wu, Kun Tian, Wenqiang Bao, Pengming Sun and An Zhu
Toxics 2024, 12(5), 339; https://doi.org/10.3390/toxics12050339 - 7 May 2024
Cited by 3 | Viewed by 1994
Abstract
Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin [...] Read more.
Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, β-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/β-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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17 pages, 7132 KiB  
Article
Biochemical Toxicological Study of Insulin Overdose in Rats: A Forensic Perspective
by Cunhao Bian, Xin He, Qi Wang, Zhe Zheng, Yongtai Zhang, Hongli Xiong, Yongguo Li, Mingzhu Zhao and Jianbo Li
Toxics 2024, 12(1), 17; https://doi.org/10.3390/toxics12010017 - 23 Dec 2023
Cited by 1 | Viewed by 2215
Abstract
Due to nonspecific pathological changes and the rapid degradation of insulin in postmortem blood samples, the identification of the cause of death during insulin overdose has always been a difficulty in forensic medicine. At present, there is a lack of studies on the [...] Read more.
Due to nonspecific pathological changes and the rapid degradation of insulin in postmortem blood samples, the identification of the cause of death during insulin overdose has always been a difficulty in forensic medicine. At present, there is a lack of studies on the toxicological changes and related mechanisms of an insulin overdose, and the specific molecular markers of insulin overdose are still unclear. In this study, an animal model of insulin overdose was established, and 24 SD rats were randomly divided into a control group, insulin overdose group, and a recovery group (n = 8). We detected the biochemical changes and analyzed the toxicological mechanism of an insulin overdose. The results showed that after insulin overdose, the rats developed irregular convulsions, Eclampsia, Opisthotonos, and other symptoms. The levels of glucose, glycogen, and C-peptide in the body decreased significantly, while the levels of lactate, insulin, and glucagon increased significantly. The decrease in plasma K+ was accompanied by the increase in skeletal muscle K+. The PI3K-AKT signaling pathway was significantly activated in skeletal muscle, and the translocation of GLUT4/Na+-K+-ATPase to sarcolemma was significantly increased. Rare glycogenic hepatopathy occurred in the recovery group after insulin overdose. Our study showed that insulin overdose also plays a role in skeletal muscle cells, mainly through the PI3K-Akt signaling pathway. Therefore, the detection of signaling pathway proteins of the skeletal muscle cell membrane GLUT4 and Na+-K+-ATPase has a certain auxiliary diagnostic value for forensic insulin overdose identification. Glycogen detection in the liver and skeletal muscle is important for the diagnosis of insulin overdose, but it still needs to be differentiated from other causes of death. Skeletal muscle has great potential for insulin detection, and the ratio of insulin to the C-peptide (I:C) can determine whether an exogenous insulin overdose is present. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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Review

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11 pages, 1137 KiB  
Review
The Perils of Methanol Exposure: Insights into Toxicity and Clinical Management
by Mohammed Alrashed, Norah S. Aldeghaither, Shatha Y. Almutairi, Meshari Almutairi, Abdulrhman Alghamdi, Tariq Alqahtani, Ghada H. Almojathel, Nada A. Alnassar, Sultan M. Alghadeer, Abdulmajeed Alshehri, Mohammed Alnuhait and Omar A. Almohammed
Toxics 2024, 12(12), 924; https://doi.org/10.3390/toxics12120924 - 20 Dec 2024
Viewed by 1218
Abstract
Methanol is a widely used industrial and household alcohol that poses significant health risks upon exposure. Despite its extensive use, methanol poisoning remains a critical public health concern globally, often resulting from accidental or intentional ingestion and outbreaks linked to contaminated beverages. Methanol [...] Read more.
Methanol is a widely used industrial and household alcohol that poses significant health risks upon exposure. Despite its extensive use, methanol poisoning remains a critical public health concern globally, often resulting from accidental or intentional ingestion and outbreaks linked to contaminated beverages. Methanol toxicity stems from its metabolic conversion to formaldehyde and formic acid, leading to severe metabolic acidosis and multiorgan damage, including profound CNS effects and visual impairments. Epidemiological data underscore the widespread impact of methanol poisoning, with alarming case fatality rates reported in various countries. Comprehensive prevention and effective management strategies are urgently needed to address the significant morbidity and mortality associated with methanol poisoning. The clinical manifestations of methanol toxicity vary between adult and pediatric populations and between acute and chronic exposure. Adults typically present with gastrointestinal and neurological symptoms, whereas pediatric patients often exhibit more severe outcomes due to differences in metabolism and body weight. The diagnosis of methanol poisoning involves a combination of clinical evaluation, laboratory testing, and advanced diagnostic techniques. The identification of metabolic acidosis, elevated anion and osmolal gaps, and confirmation through methanol and formate levels are critical for accurate diagnosis. Timely intervention is crucial, and the management of methanol poisoning includes securing the airway, breathing, and circulation; addressing metabolic acidosis with sodium bicarbonate; administering antidotes such as fomepizole or ethanol; and administering hemodialysis, which plays a pivotal role in eliminating methanol and its toxic metabolites, especially in severe cases. The complexity of methanol poisoning necessitates a comprehensive approach encompassing early recognition, prompt intervention, and coordinated care among healthcare providers. Increased awareness, effective prevention strategies, and timely treatment protocols are essential to mitigate severe health consequences and improve patient survival and recovery. Full article
(This article belongs to the Special Issue Drug Metabolism and Toxicological Mechanisms)
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