title: Effect of microsomal enzyme inducers and inhibitors on the toxicity of tunicamycin and corynetoxin, the causal agent of annual ryegrass toxicity.
abstract: 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.
mesh_terms: 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*
chemical_list: D004791:Enzyme Inhibitors; D006017:Glycolipids; D014118:Toxins, Biological; C034696:corynetoxins; D014415:Tunicamycin; D003577:Cytochrome P-450 Enzyme System