RESUMO
In order to investigate the pathogenic mechanism responsible for liver injury associated with chronic alcoholism, we studied the effects of different dietary vitamin E levels in chronically ethanol (EtOH)-fed rats on the activity and mRNA regulation of the manganese superoxide dismutase (MnSOD) enzyme. Evidence is accumulating that intermediates of oxygen reduction may in fact be associated with the development of alcoholic liver disease. Since low vitamin E liver content seems to potentiate EtOH-linked oxidative stress, we studied the effect of EtOH treatment in livers from rats fed a diet deficient or supplemented with vitamin E. Chronic EtOH feeding enhanced hepatic consumption of vitamin E in both groups of EtOH-treated animals, irrespectively of the vitamin E level of the basal diet and the effect was observed in both the microsomal and mitochondrial fractions. Both EtOH-fed groups exhibited increased MnSOD gene expression, while the enzyme activity was enhanced only in the vitamin E-deprived group of EtOH-treated animals. The significant increase in manganese liver content found only in this last group could explain the rise of enzyme activity. In fact, in the absence of a parallel increase of the prosthetic ion manganese, MnSOD mRNA induction was not accompanied by a higher enzymatic activity. These findings support the role of oxidative alteration in the EtOH-induced chronic hepatotoxicity in which MnSOD response might represent a primary defence mechanism against the damaging effect of oxygen radical species.
Assuntos
Alcoolismo , Modelos Animais de Doenças , Etanol/farmacologia , Alimentos Formulados , Superóxido Dismutase/efeitos dos fármacos , Deficiência de Vitamina E/diagnóstico , Vitamina E/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Doença Crônica , Masculino , RNA Mensageiro/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
1. Livers from rats treated acutely with ethanol showed increased chemiluminescence, malondialdehyde production, and diene formation. Previous administration of (+)-cyanidanol-3 completely abolished acute ethanol-induced chemiluminescence. 2. Rats fed alcohol liquid diets for 3 weeks showed significant increases in microsomal and mitochondrial malondialdehyde formation, and in microsomal H2O2 and O2-. generation. 3. Rats fed a solid basal diet plus ethanol solution for 12 weeks also showed increased microsomal production of O2-. and increased content of microsomal cytochrome P-450. Hydroperoxide-induced chemiluminescence was higher in homogenates, mitochondria and microsomes from ethanol-treated rats than from controls. Vitamins E and A were more effective inhibitors of hydroperoxide-stimulated chemiluminescence in liver homogenates from ethanol-treated rats than from control animals. 4. Results are consistent with peroxidative stress leading to increased lipid peroxidation in liver of rats fed ethanol both acutely and after long-term dosing.