Effect of desferrioxamine on the development of hexachlorobenzene-induced porphyria.
The present work deals with the effect of desferrioxamine (DF) on hexachlorobenzene (HCB)-induced porphyria in female rats with the purpose of further investigation of the role of iron in the development of this porphyria. The results obtained show that the repeated injection of DF (three times a week: 100 mg/kg each i.m.) delayed and diminished remarkably the urinary excretion of precursors and porphyrins as well as the accumulation of the latter in liver promoted by HCB (1 g/kg daily given by stomach tube). This was probably due to attenuation by DF of the alterations produced by the fungicide in the two key enzymes: porphyrinogen carboxy-lyase (PCL) and delta-aminolaevulinate synthase (ALA-S). In fact, DF by reducing liver iron levels produced a smaller decrease of the target enzyme (PCL) and a concomitant smaller induction of ALA-S. DF alone did not modify any of these variables or the liver to body weight ratio. DF added at 10(-2) and 10(-3) M to the incubation media of ALA-S and PCL did not alter either of the enzymatic activities, whether in normal or HCB-porphyric preparations. The results obtained show that DF improved the biochemical picture during HCB porphyria. They suggest that iron plays an indirect role in the decrease of PCL enzyme, possibly at the HCB metabolization step. A common iron-involving mechanism for the production of porphyria by different chlorinated compounds is suggested.
D000624:5-Aminolevulinate Synthetase / Q000037:antagonists & inhibitors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D002722:Chlorobenzenes / Q000633:toxicity*; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal / Q000378:metabolism; D005260:Female; D006581:Hexachlorobenzene / Q000378:metabolism / Q000633:toxicity*; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011164:Porphyrias / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D012871:Skin Diseases / Q000378:metabolism
D002722:Chlorobenzenes; D011166:Porphyrins; D006581:Hexachlorobenzene; D007501:Iron; D000624:5-Aminolevulinate Synthetase; D002262:Carboxy-Lyases; C022430:porphyrinogen carboxy-lyase; D003676:Deferoxamine