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Category:Spanish gastroenterologistsInduction of a cholestatic pattern in rat hepatocytes by treatment with 1,2-naphthoquinone, the active metabolite of mefenamic acid.
The drug mefenamic acid is widely used to induce cytochrome P450 (CYP) 3A in order to increase the clearance of certain drugs, such as cyclosporin and tacrolimus, used in transplantation. However, in the clinic, toxicity, such as rash and fever, has been reported in several patients taking mefenamic acid. We treated rat hepatocytes in vitro with mefenamic acid and its metabolite 1,2-naphthoquinone (1,2-NQ), and evaluated the levels of inducible CYP3A and changes in cytotoxicity. 1,2-NQ markedly increased the level of inducible CYP3A activity, a marker of CYP3A, in a dose-dependent manner. The activities of CYP3A and CYP2B1 were significantly decreased, suggesting that the effects of 1,2-NQ were not specific to CYP3A. Additionally, 1,2-NQ induced changes in cytotoxicity similar to those reported in patients taking mefenamic acid. However, other basic toxicity factors, such as pyridine nucleotides and glutathione, remained at low levels. Thus, the cytotoxicity induced by mefenamic acid may be due to the 1,2-NQ metabolite. In conclusion, mefenamic acid and its metabolite 1,2-NQ induced cytotoxicity in cultured hepatocytes, leading to a reduction in the cytochrome P450 enzyme activity.Axonal growth is a process of fundamental importance in the development of the nervous system and may play an equally important role in the maintenance of the nervous system in the adult. Various growth promoting factors have been studied, but a more complete understanding of the mechanisms by which axons grow and target specific structures is needed. Previous studies have shown that fibroblasts derived from different embryonic tissues stimulate neural differentiation of neuroblastoma cells and that the effects of these "trophic" factors can be mimicked by homologous factors present in extracts of various organs be359ba680
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