Effects of acetysal, dexamethasone and their combination on drug metabolizing enzyme systems in rat liver microsomes.
After 4 days of acetysal treatment (160 mg/kg body weight orally), the following were established: a higher acute toxicity of acetysal, an inducing effect on amidopyrin N-demethylase and analgin N-demethylase activity and increases in cytochrome P-450 and cytochrome b5 content. Aniline hydroxylase activity decreased, thiopental sleeping time was prolonged and UDP-glucuronyltransferase activity was not changed. Dexamethasone, at a dose of 5 mg/kg body weight p.o. for 4 days, did not change acetysal acute toxicity but at a dose of 100 mg/kg i.p. increased it. Thiopental sleeping time was shortened by dexamethasone (100 mg/kg i.p.) but was not changed by dexamethasone at 5 mg/kg p.o., alone or in combination. Dexamethasone at 5 mg/kg increased analgin N-demethylase and UDP-glucuronyltransferase activities, did not change cytochrome P-450 content and decreased aniline hydroxylase activity. The combination with 5 mg/kg dexamethasone increased the activity of amidopyrin N-demethylase, analgin N-demethylase and UDP-glucuronyltransferase and decreased those of amitriptyllin N-demethylase and aniline hydroxylase and cytochrome P-450 content. Ethylmorphine N-demethylase, benzphetamine N-demethylase, NADPH-cytochrome c reductase and glutathione S-transferase activities were not affected significantly by acetysal, dexamethasone or their combination. Hepatic carboxyl esterase was depressed by dexamethasone (5 mg/kg) and was increased by the combination. Lipid peroxidation was not changed by dexamethasone (5 mg/kg) but was decreased by acetysal and the combination.
Tantcheva
L P
LP
Department of Drug Toxicology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Rangelova
D S
DS
Stoytchev
T S
TS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000506:poisoning; D001241:Aspirin / Q000494:pharmacology* / Q000506:poisoning; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D005938:Glucocorticoids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D003907:Dexamethasone; D001241:Aspirin