ArticleThe Journal of clinical investigation1996
Antigenic targets in tienilic acid hepatitis. Both cytochrome P450 2C11 and 2C11-tienilic acid adducts are transported to the plasma membrane of rat hepatocytes and recognized by human sera.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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Who cites it
11 citing papers in PubMed, 78 citations in OpenAlex.
- Modeling the Bioactivation and Subsequent Reactivity of Drugs.Chemical research in toxicology · 2021Article
- The Immunological Mechanisms and Immune-Based Biomarkers of Drug-Induced Liver Injury.Frontiers in pharmacology · 2021Review
- Irreversible Enzyme Inhibition Kinetics and Drug-Drug Interactions.Methods in molecular biology (Clifton, N.J.) · 2021Article
- XenoNet: Inference and Likelihood of Intermediate Metabolite Formation.Journal of chemical information and modeling · 2020Article
- Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications.Acta pharmaceutica Sinica. B · 2020Review
- The functional effects of physical interactions involving cytochromes P450: putative mechanisms of action and the extent of these effects in biological membranes.Drug metabolism reviews · 2016Review
- Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure.Hepatology (Baltimore, Md.) · 2014Article
- Idiosyncratic adverse drug reactions: current concepts.Pharmacological reviews · 2013Review
- Xenobiotic-metabolizing enzymes as autoantigens in human autoimmune disorders. An update.Clinical reviews in allergy & immunology · 2000Review
- Article
- Drug-induced immunotoxicity.European journal of drug metabolism and pharmacokineticsReview
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with tienilic acid hepatitis exhibit autoantibodies that recognize unalkylated cytochrome P450 2C9 in humans but recognize 2C11 in rats. Our aim was to determine whether the immune reaction is also directed against neoantigens. Rats were treated with tienilic acid and hepatocytes were isolated. Immunoprecipitation, immunoblotting, and flow cytometry experiments were performed with an anti-tienilic acid or an anti-cytochrome P450 2C11 antibody. Cytochrome P450 2C11 was the main microsomal or plasma membrane protein that was alkylated by tienilic acid. Inhibitors of vesicular transport decreased flow cytometric recognition of both unalkylated and tienilic acid-alkylated cytochrome P450 2C11 on the plasma membrane of cultured hepatocytes. Tienilic acid hepatitis sera that were preadsorbed on microsomes from untreated rats (to remove autoantibodies), poorly recognized untreated hepatocytes in flow cytometry experiments, but better recognized tienilic acid-treated hepatocytes. This recognition was decreased by adsorption with tienilic acid or by preexposure to the anti-tienilic acid or the anti-cytochrome P450 2C11 antibody. We conclude that cytochrome P450 2C11 is alkylated by tienilic acid and follows a vesicular route to the plasma membrane. Tienilic acid hepatitis sera contain antibodies against this tienilic acid adduct, in addition to the previously described anticytochrome P450 autoantibodies.
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