Effects of intermittent styrene inhalation, ethanol intake and their combination on drug biotransformation in rat liver and kidneys.
The modifying effects of daily ethanol ingestion in the drinking water as a 15 % solution (v/v) on drug biotransformational changes induced by inhalation exposure to styrene (300 ppm or 1260 mg/m3, 6 h daily, 5 d/week, up to 17 weeks) were studied in rat liver and kidney. The drug hydroxylation activities (7-ethoxycoumarin O-deethylase and 2,5-diphenyloxazole hydroxylase) both in liver and in kidneys were increased more by ethanol ingestion than by styrene inhalation. When administered in combination, styrene and ethanol exerted mostly an additive enhancing effect. However, hepatic NADPH-cytochrome c reductase activity was reduced both in styrene and in ethanol-treated rats. Hepatic styrene oxide hydratase activity was virtually unaffected by styrene treatments. The depression of glutathione concentration in liver was greater after styrene-ethanol than after styrene treatment alone. The hepatic UDPglucuronosyltransferase activity was enhanced slightly both in styrene and in styrene-ethanol rats. The binding affinity of styrene towards cytochrome P-450 was increased after styrene inhalation as shown by lowered K8 values. The perirenal fat concentration of styrene showed a rough inverse relationship to the overall monooxygenation activities in liver and kidney. Despite the additively induced enzyme activities in styrene-ethanol-treated rats the accumulation of styrene in fat of these animals was on the whole somewhat greater, suggesting that these two solvents in vivo also have mutual inhibitory effects on biotransformation.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D013343:Styrenes / Q000494:pharmacology*
D013343:Styrenes; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; D014453:Glucuronosyltransferase; D004851:Epoxide Hydrolases; D005978:Glutathione