Cisplatin-induced changes in cytochrome P-450, lipid peroxidation and drug-metabolizing enzyme activities in rat kidney cortex.
This study investigates the effects of 3 successive cisplatin administrations on rat kidney cytochrome P-450 and drug-metabolizing enzyme activities. Furthermore, because glutathione (GSH) and its related enzymatic system are involved in cellular detoxification processes, we examined the effects of cisplatin on lipid peroxidation, GSH levels, and GSH reductase and peroxidase activities. Cisplatin induced a decrease in cytochrome P-450, GSH, GSH S-transferase, GSH reductase and GSH peroxidase activities, and an increase in N-glucuronyl transferase, lipid peroxidation and oxidized glutathione (GSSG) in kidney cortical microsomes and cytosolic fractions. It is suggested that cisplatin nephrotoxicity could be explained by its affinity for SH-groups of several enzymes and SH-containing compounds. Among these, GSH and its related enzymatic system play a primary role. Moreover, cisplatin increases lipid peroxidation, which might participate in cisplatin nephrotoxicity.
INSERM U-133, Toulouse, (France).
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D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism / Q000502:physiology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008658:Inactivation, Metabolic; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D051381:Rats
D008054:Lipid Peroxides; D003577:Cytochrome P-450 Enzyme System; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin