Acute gene induction by tienilic acid in the male Sprague Dawley rat:  Possible role for danger.
Published: 2006
Language: eng
Number of pages: 73
ISBN-13: 9780494213582
Description: Tienilic acid (TA) was withdrawn from the market due to numerous cases of liver necrosis [1]. TA appears to act as a hapten, however it is unlikely that covalent binding to the enzyme metabolizing TA, CYP 2C9, would lead to significant cell stress. We used microarray analysis to determine if TA caused changes in gene expression that suggests an induction of cell stress that could act as a danger signal. Sprague Dewitt rats were dosed with TA, hepatic gene expression was profited at 6 and 24 hours, and microarray data were substantiated by qRT-PCR. This experiment was repeated at 6 hours, using qRT-PCR to verify gene changes from the previous study. Results showed robust changes in genes involved in oxidative stress, inflammation and liver regeneration. These data are consistent with the hypothesis that danger signals in the form of cell-stress proteins may be involved in initiating TA-induced toxicity.
Notes: Source: Masters Abstracts International, Volume: 45-03, page: 1490.

Thesis (M.Sc.)--University of Toronto, 2006.

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