Effect of microsomal enzyme inducers and inhibitors on the toxicity of tunicamycin and corynetoxin, the causal agent of annual ryegrass toxicity.
Of the microsomal enzyme inducers and inhibitors tested in rats, the only one to modify the toxicity of tunicamycin or the closely-related corynetoxin, the causal agent of annual ryegrass toxicity, was phenobarbitone. It increased the LD50 of tunicamycin from 0.31 mg/kg to 0.77 mg/kg. Similar results were obtained with the related corynetoxin. Tunicamycin was also shown to be an inhibitor of cytochromes P-450. Rats sacrificed 48 h after receiving an LD50 dose of tunicamycin had cytochromes P-450 levels 30% that of controls. Rats pretreated with trans-stilbene oxide, which like phenobarbitone is an inducer of glutathione transferase, showed no decreased susceptibility to tunicamycin. These results suggest that neither hepatic cytochromes P-450 enzymes nor glutathione transferase is involved in detoxication of tunicamycin or corynetoxin in rats. The beneficial effect of phenobarbitone may be the result of a special kind of phenobarbitone-inducible enzyme which may not be P-450 dependent.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006017:Glycolipids / Q000378:metabolism / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D014118:Toxins, Biological / Q000378:metabolism / Q000633:toxicity*; D014415:Tunicamycin / Q000378:metabolism / Q000633:toxicity*
D004791:Enzyme Inhibitors; D006017:Glycolipids; D014118:Toxins, Biological; C034696:corynetoxins; D014415:Tunicamycin; D003577:Cytochrome P-450 Enzyme System