The potent heme oxygenase inducing action of arsenic and parasiticidal arsenicals.
The administration of trivalent arsenic, either as sodium arsenite or as the trypanocidal drug melarsoprol, to rats produced a profound induction of microsomal heme oxygenase (EC 1.14.99.3) in both liver and kidney and a concomitant decrease in cytochrome P-450 content. In addition, perturbations of delta-aminolevulinate synthase were observed which showed an initial decline followed by a rebound increase in the activity of this enzyme with arsenical treatment. Pentavalent arsenic did not induce hepatic heme oxygenase but did induce the enzyme in kidney, although to a lesser extent (50%) than trivalent arsenic. Treatment of isolated chick embryo liver cells in vitro with sodium arsenite or the parasiticidal drug melarsoprol also showed a potent induction of heme oxygenase. These findings describe a new and potent ability of arsenic and parasiticidal arsenicals to induce heme oxygenase resulting in enhanced degradation of cellular heme.
D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D001152:Arsenicals / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014344:Trypanocidal Agents / Q000494:pharmacology
D001152:Arsenicals; D014344:Trypanocidal Agents; D006418:Heme; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D001151:Arsenic