Evidence map›Paper›PMID 22867114›Full record

ArticleChemical research in toxicology2012

Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes.

Heather Hajovsky, Gang Hu, Yakov Koen, Diganta Sarma, Wenqi Cui, David S Moore, Jeff L Staudinger, Robert P Hanzlik

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
9.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 194 citations in OpenAlex.

  1. Article
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  6. Preclinical mouse models for studying cholangiocarcinoma.Liver research (Beijing, China) · 2026
    Review
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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Heather HajovskyDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, KA 66045, USA.
Gang Hu
Yakov Koen
Diganta Sarma
Wenqi Cui
David S Moore
Jeff L Staudinger
Robert P Hanzlik
University of Kansas · US

Funding

ROLE OF EPOXIDES IN METABOLISM AND DRUG TOXICITYR01GM021784 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI HANZLIK, ROBERT P · 1985 to 2012
$2.9M
NIGMS NIH HHS GM-21784NIGMS NIH HHS R01 GM021784
6 · The paper itself

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.

Indexed as

AnimalsCells, CulturedCytochrome P-450 CYP2E1Cytochrome P-450 CYP2E1 InhibitorsHepatocytesL-Lactate DehydrogenaseMaleRatsRats, Sprague-DawleyThioacetamideCytochrome P-450 CYP2E1Cytochrome P-450 CYP2E1 InhibitorsL-Lactate DehydrogenaseThioacetamidethioacetamide-S-oxide

Identifiers

PMID22867114
PMCPMC3444651
OpenAlexW2057070400

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.