Regulation of heme metabolism and monooxygeneses in liver and kidney: influence of therapeutically used gold compounds.
Two gold compounds, gold sodium thiomalate (AuTM) and auranofin (AF) are presently in clinical use in therapy of rheumatoid arthritis. The effects of varying doses of AF administered to rats by either the p.o. or the i.p. route on heme metabolism were determined. Twenty four hours after a single dose of AF, decreases in the sulfhydryl-containing enzymes, delta-aminolevulinic acid dehydratase and ferrochelatase activities were observed in the liver and kidneys. These decreases in heme biosynthetic enzymes were accompanied by decreases in cytochrome P-450-dependent enzymic activities and increases in microsomal heme oxygenase activity. These changes were observed with AF dosages as low as 5 mg/kg, with maximal changes occurring at a p.o. dose of about 15 mg of AF per kg and an i.p. dose of 5 to 10 mg of AF per kg. Dose-response studies with AuTM showed that maximal changes in heme metabolism occur at a lower dose of AF than of AuTM, even though AF was administered p.o. and AuTM was administered parenterally. In addition, the kidneys appeared to be more susceptible to the inhibitory effects of the two chrysotherapeutic agents than did the liver. The present studies demonstrate the p.o. drug AF affects heme metabolism in a manner similar to that reported previously with the parenterally administered AuTM.
D000818:Animals; D001310:Auranofin / Q000633:toxicity*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D006052:Gold Sodium Thiomalate / Q000633:toxicity*; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010105:Oxygenases / Q000378:metabolism*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006052:Gold Sodium Thiomalate; D001310:Auranofin; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D001579:Benzopyrene Hydroxylase; D006419:Heme Oxygenase (Decyclizing); D005037:Ethylmorphine-N-Demethylase; D000623:Porphobilinogen Synthase