ArticleChemical research in toxicology2012
Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes.
Article in Chemical research in toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 194 citations in OpenAlex.
- Visnagin Attenuates Thioacetamide-Induced Liver Injury and Fibrosis Through the Modulation of TLR4-Mediated Inflammation and Downregulation of TGF-β/α-SMA-Driven Fibrogenesis.Journal of applied toxicology : JAT · 2026Article
- Neuroprotective effects of zingerone on the thioacetamide-induced hepatic encephalopathy in rats. Insights from oxidative stress, ER stress, BDNF signaling and apoptosis.Journal of molecular histology · 2026Article
- Revisiting two-stage models of chemically-induced cirrhosis-associated hepatocarcinogenesis in rodents: methodological and histopathological approaches.Journal of molecular histology · 2026Review
- Probing the Interaction Between Thioacetamide Fungicide and Bovine Serum Albumin Through Fluorescence, Electrochemical, and Docking Analyses.Luminescence : the journal of biological and chemical luminescence · 2026Article
- Visnagin attenuates thioacetamide-induced kidney damage through suppression of renal injury marker, oxidative stress, inflammation, apoptosis, and TGF-β-mediated renal fibrosis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Preclinical mouse models for studying cholangiocarcinoma.Liver research (Beijing, China) · 2026Review
- Protective Role of Coffee in Thioacetamide-induced Nephrotoxicity: A Study in Rats.Current pharmaceutical biotechnology · 2026Article
- Hepatoprotective effect of diosmetin against thioacetamide-induced liver injury via modulating Bax/NF-κB/caspase-3/Nrf-2/PPARNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Pentadecanoic acid attenuates thioacetamide-induced liver fibrosis by modulating oxidative stress, inflammation, and ferroptosis pathways in rat.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Macrophage Inhibitory Factor in Myocardial Oxidative Stress and Inflammation During Thioacetamide-Induced Liver Fibrosis: Modulation by Betaine.Current issues in molecular biology · 2025Article
- Allopurinol abates hepatocellular carcinoma in rats via modulation of NLRP3 inflammasome and NF-κB pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Time-course of changes in fibrous components in a thioacetamide-induced liver fibrosis model in cynomolgus monkeys.Journal of toxicologic pathology · 2025Article
- Article
- High mobility group box1 as a danger signal inducing the infiltration of neutrophils and macrophages in thioacetamide-induced rat liver injury.Journal of toxicologic pathology · 2025Article
- Understanding and using Animal Models of Hepatotoxicity.Current pharmaceutical design · 2025Review
- Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure.Nature communications · 2024Article
- Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model.Clinical science (London, England : 1979) · 2024Article
- Liver fibrosis pathologies and potentials of RNA based therapeutics modalities.Drug delivery and translational research · 2024Review
- Neuroprotective and cognitive enhancing effects of herbecetin against thioacetamide induced hepatic encephalopathy in rats via upregulation of AMPK and SIRT1 signaling pathways.Scientific reports · 2024Article
- Hepatoprotective activity of Lactéol® forte and quercetin dihydrate against thioacetamide-induced hepatic cirrhosis in male albino rats.Journal of cellular and molecular medicine · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The hepatotoxicity of thioacetamide (TA) has been known since 1948. In rats, single doses cause centrolobular necrosis accompanied by increases in plasma transaminases and bilirubin. To elicit these effects, TA requires oxidative bioactivation, leading first to its S-oxide (TASO) and then to its chemically reactive S,S-dioxide (TASO(2)), which ultimately modifies amine-lipids and proteins. To generate a suite of liver proteins adducted by TA metabolites for proteomic analysis and to reduce the need for both animals and labeled compounds, we treated isolated hepatocytes directly with TA. Surprisingly, TA was not toxic at concentrations up to 50 mM for 40 h. On the other hand, TASO was highly toxic to isolated hepatocytes as indicated by LDH release, cellular morphology, and vital staining with Hoechst 33342/propidium iodide. TASO toxicity was partially blocked by the CYP2E1 inhibitors diallyl sulfide and 4-methylpyrazole and was strongly inhibited by TA. Significantly, we found that hepatocytes produce TA from TASO relatively efficiently by back-reduction. The covalent binding of [(14)C]-TASO is inhibited by unlabeled TA, which acts as a "cold-trap" for [(14)C]-TA and prevents its reoxidation to [(14)C]-TASO. This in turn increases the net consumption of [(14)C]-TASO despite the fact that its oxidation to TASO(2) is inhibited. The potent inhibition of TASO oxidation by TA, coupled with the back-reduction of TASO and its futile redox cycling with TA, may help explain phenomena previously interpreted as "saturation toxicokinetics" in the in vivo metabolism and toxicity of TA and TASO. The improved understanding of the metabolism and covalent binding of TA and TASO facilitates the use of hepatocytes to prepare protein adducts for target protein identification.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.