Effect of adaptive steroids on the impairment of hepatic drug metabolic activity caused by hepatotoxic agents.
Hepatic disfunction was produced in female rats by ethanol, carbon tetrachloride, dimethyl mercury or Freund's Adjuvant. This disfunction was expressed by increased SGPT, liver triglycerides level, and reduced resistance to zoxazolamine, digitoxin and indomethacin. Treatment with spironolactone, pregnenolone-16_-carbonitrile or triamcinolone reduced only slightly SGPT and triglycerides, but restored the reduced resistance to drugs, and the impairment of the liver drug metabolism in vitro. Triamcinolone was the least effective. Spironolactone, pregnenolone-16_-carbonitrile and triamcinolone were most active in preventing the hepatotoxicity of dimethyl mercury, of carbon tetrachloride and of Freund's Adjuvant respectively. Restoration of drug metabolism is attributed to the microsomal enzyme induction in general. Triamcinolone, when potent in rats with adjuvant induced disease (AID), acted by a glycocorticoid mediated mechanism. In AID, treatment of inflammation restored liver drug metabolism, but restoration of the hepatic drug metabolic activity in AID rats only slightly ameliorated inflammation. None of the tested steroids demonstrated any activity against lipid peroxidation, thus excluding any mediation of a free radical mechanism in spironolactone, PCN or triamcinolone involvement in drug response and metabolism of the damaged liver by the hepatotoxic agents used.
Kourounakis
P N
PN
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Thessaloniki, Greece.
Rekka
E
E
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008111:Liver Function Tests; D009929:Organ Size / Q000187:drug effects; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology*; D014221:Triamcinolone / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D013256:Steroids; D014280:Triglycerides; D011285:Pregnenolone Carbonitrile; D014221:Triamcinolone; D013148:Spironolactone; D000410:Alanine Transaminase