Effect of an iron chelator on the onset of hexachlorobenzene-induced porphyria in rats.
The effect of desferrioxamine on hexachlorobenzene (HCB)-induced porphyria was studied in female rats in order to investigate the role of iron in the development of this porphyria. Repeated injections of desferrioxamine delayed and remarkably diminished the urinary excretion of precursors and porphyrins and the accumulation of porphyrins in the liver. These effects were produced because the desferrioxamine attenuated the alterations produced by HCB in two key enzymes: porphyrinogen carboxy-lyase and delta-aminolaevulinic acid synthase. The effect of desferrioxamine on both enzymes was also studied in vitro. This work showed that iron plays an important role in the onset of HCB-induced porphyria and supplied information on the mechanism of action. A common iron-involving mechanism for the production of porphyria by different chlorinated compounds is suggested.
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D002722:Chlorobenzenes / Q000633:toxicity*; D003676:Deferoxamine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006581:Hexachlorobenzene / Q000633:toxicity*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D011164:Porphyrias / Q000139:chemically induced* / Q000201:enzymology; D051381:Rats
D002722:Chlorobenzenes; D007502:Iron Chelating Agents; D006581:Hexachlorobenzene; D000624:5-Aminolevulinate Synthetase; D002262:Carboxy-Lyases; C022430:porphyrinogen carboxy-lyase; D003676:Deferoxamine