Further evidence for the participation of 5 beta-steroids in the development of a porphyria induced by hexachlorobenzene.
Adult female rats were fed with a diet containing hexachlorobenzene to induce a porphyria. 5 alpha/5 beta-ratios of androstane steroids in blood were 0.61 +/- 0.13 in porphyric rats and 1.05 +/- 0.35 in normal rats. Etiocholanolone treatment of rats was ineffective in generation of a porphyria. The activity of microsomal glucuronyltransferase increased from 0.20 +/- 0.04 mU/mg to 0.77 +/- 0.23 mU/mg by this treatment. Administration of Flutamide (4'-nitro-3'-trifluoromethylisobutyranilide) to porphyric rats resulted in a decline of porphyrin excretion by 55%. The hepatic NADH-5 beta-reductase was strongly inhibited by this drug, whereas NADPH-5 beta-reductase displayed a slightly increased activity. These findings are further evidence for the involvement of 5 beta-steroids in the formation of porphyria.
D000818:Animals; D002722:Chlorobenzenes / Q000009:adverse effects*; D005043:Etiocholanolone / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D006581:Hexachlorobenzene / Q000009:adverse effects*; D008099:Liver / Q000378:metabolism; D010088:Oxidoreductases / Q000032:analysis; D011164:Porphyrias / Q000139:chemically induced*; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D013256:Steroids / Q000378:metabolism
D002722:Chlorobenzenes; D011166:Porphyrins; D013256:Steroids; D006581:Hexachlorobenzene; C006576:androstane-3,17-dione; D005485:Flutamide; D005043:Etiocholanolone; D010088:Oxidoreductases; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase