[Effect of thiol compounds on experimental liver damage (III). Effect of tiopronin (2-mercaptopropionylglycine) and glutathione on drug metabolizing activity (author's transl)].
In our previous papers, tiopronin (2-mercaptopropionylglycine) and glutathione were reported to suppress the liver damage induced by ethionine. In the damage induced by ethionine. In the present study, we evaluated such suppressive effect from the aspect of drug metabolizing activity. Aniline hydroxylating enzyme activity and aminopyrine N-demethylating enzyme activity of the liver microsome of rats 24 hr after administration of 1 g/kg ethionine were decreased to 53.2% and 61.7% respectively as compared with those of the normal rats. Administration of tiopronin or glutathione to the ethionine treated rats suppressed the decrease of both enzyme activities induced by ethionine. Ethionine did not influence NADH-cytochrome c reductase (fp1) but brought about increase of the activity of NADPH-cytochrome c reductase (fp2) and decrease of the cytochrome P-450 content. These thiol compounds did not influence fp1 and fp2 but tended to suppress the cytochrome P-450 content decreased by administration of ethionine. In particular, tiopronin suppressed the content significantly. Disappearance of aminopyrine, hexobarbital and pentobarbital from the blood was markedly delayed by ethionine administration. It was revealed, however, that such delay was recovered by tiopronin or glutathione. The sleeping time induced by hexobarbital and pentobarbital was also prolonged by ethionine, but this tended to be shortened by tiopronin or glutathione.
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000632:Aminopyrine / Q000097:blood; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005001:Ethionine; D005260:Female; D005978:Glutathione / Q000494:pharmacology*; D006591:Hexobarbital / Q000097:blood; D008107:Liver Diseases / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology*; D009245:NADH Dehydrogenase / Q000032:analysis; D009251:NADPH-Ferrihemoprotein Reductase / Q000032:analysis; D010424:Pentobarbital / Q000097:blood; D051381:Rats; D012890:Sleep / Q000187:drug effects; D008625:Tiopronin / Q000008:administration & dosage / Q000494:pharmacology*
D000603:Amino Acids, Sulfur; D000632:Aminopyrine; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D008625:Tiopronin; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase; D009245:NADH Dehydrogenase; D005978:Glutathione; D010424:Pentobarbital; D005001:Ethionine