Effect of heme on allylisopropylacetamide-induced changes in heme and drug metabolism in the rhesus monkey (Macaca mulatta).
In rhesus monkeys, in which porphyria was induced by the administration of allylisopropylacetamide (AIA), hepatic delta-aminolevulinic acid synthase (ALA-S) was increased. Cytochrome P-450 and associated monooxygenase activities and microsomal heme oxygenase activity were decreased in these animals. Administration of heme for 4 days concurrently with AIA prevented the induction of hepatic ALA-S but produced further decreases in cytochrome P-450 and monooxygenase activities. The decrease in heme oxygenase activity elicited by AIA alone was partially reversed. Administration of heme alone caused an impairment of hepatic drug metabolism but had no significant effect on heme metabolism. The porphyric monkeys showed elevation of porphyrin levels in blood and urine. When heme was administered concurrently with AIA, blood porphyrin levels were further elevated, while the urinary excretion of porphyrins was lower than that following treatment of monkeys with AIA. Following the administration of heme alone, blood and urinary porphyrin levels were minimally affected. These results suggest that repeated heme administration in the primate may adversely affect drug metabolism by the liver.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000081:Acetamides / Q000494:pharmacology*; D000502:Allylisopropylacetamide / Q000494:pharmacology*; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D005260:Female; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008253:Macaca mulatta; D008862:Microsomes, Liver / Q000201:enzymology*; D011164:Porphyrias / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism*
D000081:Acetamides; D011166:Porphyrins; D000502:Allylisopropylacetamide; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D001579:Benzopyrene Hydroxylase; D006419:Heme Oxygenase (Decyclizing); D005037:Ethylmorphine-N-Demethylase; D000624:5-Aminolevulinate Synthetase