Transcription profiling of rats after treatment with tienilic acid

ABSTRACT: Tienilic acid (TA) was withdrawn from the US market due to numerous cases of liver necrosis. Two major hypotheses currently used to understand the mechanisms of idiosyncratic reactions such as TA-induced hepatotoxicity are the hapten and danger hypotheses. Both human cytochrome (CYP) P450 2C9 and the rat ortholog CYP 2C11 metabolize TA, and it was reported that a reactive metabolite of TA binds almost exclusively to these enzymes, thus acting as a mechanism-based inhibitor. TA-induced liver toxicity is associated with antibodies against CYP 2C9, thus TA appears to act as a hapten. However, if the binding were limited to CYP 2C, it is unlikely that this would lead to significant cell stress. Thus, if TA does not cause cell stress it would suggest that a drug does not have to generate a

ORGANISM(S): Rattus norvegicus

SUBMITTER: Paul Boutros 

PROVIDER: E-GEOD-8252 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress