Studies on the etiology of trace metal-induced porphyria: effects of porphyrinogenic metals on coproporphyrinogen oxidase in rat liver and kidney.
Studies were conducted on the etiology of trace metal-induced porphyria in rats, with particular emphasis on the action of metals on hepatic and renal coproporphyrinogen oxidase. Prolonged exposure of rats to methyl mercury hydroxide or sodium arsenate at subtoxic dose levels in drinking water resulted in a progressive coproporphyrinuria, reaching highest rates of coproporphyrin excretion 5 weeks after initiation of exposure. The development of coproporphyrinuria was accompanied by substantial metal accumulation in the kidney and a significant decrease in renal, but not hepatic, coproporphyrinogen oxidase activity. During prolonged exposure to either metal, the rates of coproporphyrin excretion and metal accumulation by the kidney continued to increase for 2 to 3 weeks following maximal inhibition of renal coproporphyrinogen oxidase. Acute treatment studies and studies in vitro support the conclusion that the kidney is the principal source of excess urinary coproporphyrin during metal exposure. These observations demonstrate that metal-induced coproporphyrinuria is predominantly of renal etiology and that impairment of renal coproporphyrinogen oxidase is a principal cause of this effect.
Woods
J S
JS
Department of Environmental Health, University of Washington, Seattle 98195.
Southern
M R
MR
D000818:Animals; D001149:Arsenates / Q000633:toxicity*; D001151:Arsenic / Q000633:toxicity*; D003304:Coproporphyrinogen Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003306:Coproporphyrins / Q000652:urine; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D010088:Oxidoreductases / Q000378:metabolism*; D011164:Porphyrias / Q000139:chemically induced* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D014131:Trace Elements / Q000633:toxicity*
D001149:Arsenates; D003306:Coproporphyrins; D008767:Methylmercury Compounds; D014131:Trace Elements; C009277:sodium arsenate; D010088:Oxidoreductases; D003304:Coproporphyrinogen Oxidase; C020771:methylmercury hydroxide; D001151:Arsenic