Cisplatin-induced changes on cytochrome P-450, lipid peroxidation and some P-450 related specific catalytic activities in rat liver.
This study investigates the effects of three successive cisplatin administrations to rats on liver cytochrome P-450 and some related specific catalytic activities. Additionally, because glutathione and its related enzymatic system are significantly involved in cellular detoxification process, we examined the effects of cisplatin on lipid peroxidation, glutathione levels, glutathione reductase and peroxidase activities. Cisplatin induced a decrease of cytochrome P-450, glutathione-S-transferase and some cytochrome P-450 related specific catalytic activities among which aminopyrine demethylase and benzo(a)pyrene hydroxylase activities are representative of cytochrome P-450b and P-450h isoforms. Furthermore, cisplatin-induced N-glucuronyl transferase and lipid peroxidation which might participate, at least in part, in cisplatin-induced hepatotoxicity. The ability of cisplatin to cause alterations in the activity of other enzymes than those of cytochrome P-450 system suggests that cisplatin induces toxic effects in an unspecific manner.
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INSERM U 133, Faculté de Médecine, Toulouse.
D000818:Animals; D002384:Catalysis; D002945:Cisplatin / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats
D003577:Cytochrome P-450 Enzyme System; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D002945:Cisplatin