The effects of ethanol, estrogen, and hexachlorobenzene on the activities of hepatic delta-aminolevulinate synthetase, delta-aminolevulinate dehydratase, and uroporphyrinogen decarboxylase in male rats.
To determine if clinically observed disorders in heme biosynthetic enzymes, known as sporadic porphyria cutanea tarda (PCT), could be reproduced in experimental animals, male Fischer rats were treated with ethanol, estrogen and hexachlorobenzene (HCB). A series of heme biosynthetic enzymes were assayed. In the rats given free access to 8% ethanol-drinking water for 15 weeks, delta-aminolevulinate (ALA) dehydratase was significantly reduced in erythrocytes. In the liver, ALA synthetase and uroporphyrinogen (UROgen) decarboxylase activities remained unchanged. In bone marrow cells, these activities did not change markedly. In the rats treated with estrogen (1 mg estrioltripropionate/rat/week, IM), no body weight gain was observed during the treatment for 15 weeks and urinary ALA excretion increased to 1.7 fold over normal level. In the liver, a significant increase was observed in the activity of ALA dehydratase, but other enzymes remained within the normal level. In bone marrow cells and erythrocytes, ALA dehydratase was also increased. ALA synthetase increased only in bone marrow cells to 2.1 times higher than the control level. In rats fed 0.3% HCB-diet for 8 weeks, urinary excretion of ALA, coproporphyrin and uroporphyrin increased to 2.4, 3.3 and 3.8 times higher than the controls, respectively. In the liver, an increase was observed in ALA synthetase, while a decrease was observed in ALA dehydratase and UROgen decarboxylase. In bone marrow cells and erythrocytes, ALA dehydratase was reduced and activities of other enzymes did not show any changes. These results indicate that alcohol, estrogen and HCB do not produce phenomena similar to those observed clinically in PCT.
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D002722:Chlorobenzenes / Q000494:pharmacology*; D003306:Coproporphyrins / Q000652:urine; D004964:Estriol / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006581:Hexachlorobenzene / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D000623:Porphobilinogen Synthase / Q000652:urine; D011166:Porphyrins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism
D002722:Chlorobenzenes; D003306:Coproporphyrins; D011166:Porphyrins; D000431:Ethanol; D006581:Hexachlorobenzene; D000624:5-Aminolevulinate Synthetase; D014575:Uroporphyrinogen Decarboxylase; D000623:Porphobilinogen Synthase; D004964:Estriol