Heme metabolism and lipid peroxidation in rat kidney hexachlorobenzene-induced porphyria: A compartmentalized study of biochemical pathogenic mechanisms.
In the present study, the effects of hexachlorobenzene (HCB) on lipid peroxidation and heme metabolism in the different constitutive suborgans of the kidney were determined. For this purpose, conjugated diene and malondialdehyde levels, as lipid peroxidation parameters, and porphyrin accumulation, uroporphyrinogen decarboxylase activity, and its inhibitor formation, as measures of heme metabolism, were determined in renal cortex, medulla, and papilla. Adult Wistar rats were treated with HCB during 1, 2, 3, or 4 weeks. A significant increase in cortical conjugated dienes was observed from the 1st week of treatment. The malondialdehyde levels rose by 47, 34, and 28% after 2, 3, and 4 weeks of intoxication, respectively. The porphyrin content showed a tenfold increase after 4 weeks of treatment, and the uroporphyrinogen decarboxylase activity was reduced by 26 and 58% with respect to control values after 3 and 4 weeks of treatment, respectively. The results demonstrate a direct correlation between the oxidative environment and the effect elicited by the drug on heme metabolism in the renal cortex. In contrast, in papilla and medulla, where the antioxidant systems were higher, HCB showed no porphyrinogenic effect.
Fernández-Tomé
M C
MC
Departamento de Ciencias Biológicas, Cátedra de Biología Celular e Histología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIFIB-CONICET, Argentina.
Billi de Catabbi
S C
SC
Aldonatti
C
C
San Martin de Viale
L C
LC
Sterin-Speziale
N B
NB
D000818:Animals; D015415:Biomarkers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006418:Heme / Q000378:metabolism*; D006581:Hexachlorobenzene / Q000633:toxicity*; D007668:Kidney / Q000166:cytology* / Q000187:drug effects; D007672:Kidney Cortex / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014575:Uroporphyrinogen Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism
D015415:Biomarkers; D004791:Enzyme Inhibitors; D011166:Porphyrins; D006418:Heme; D008315:Malondialdehyde; D006581:Hexachlorobenzene; D014575:Uroporphyrinogen Decarboxylase