Regulation of manganese superoxide dismutase (MnSOD) in chronic experimental alcoholism: Effects of vitamin E-supplemented and -deficient diets

In order to investigate the pathogenic mechanism responsible for liver inju ry associated with chronic alcoholism, we studied the effects of different dietary vitamin E levels in chronically ethanol (EtOH)-fed rats on the acti vity and mRNA regulation of the manganese superoxide dismutase (MnSOD) enzy me. Evidence is accumulating that intermediates of oxygen reduction may in fact be associated with the development of alcoholic liver disease. Since l ow 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 de ficient or supplemented with vitamin E. Chronic EtOH feeding enhanced hepat ic consumption of vitamin E in both groups of EtOH-treated animals, irrespe ctively of the vitamin E level of the basal diet and the effect was observe d in both the microsomal and mitochondrial fractions. Both EtOH-fed groups exhibited increased MnSOD gene expression, while the enzyme activity was en hanced only in the vitamin E-deprived group of EtOH-treated animals. The si gnificant increase in manganese liver content found only in this last group could explain the rise of enzyme activity. Ln fact, in the absence of a pa rallel increase of the prosthetic ion manganese, MnSOD mRNA induction was n ot accompanied by a higher enzymatic activity. These findings support the r ole of oxidative alteration in the EtOH-induced chronic hepatotoxicity in w hich MnSOD response might represent a primary defence mechanism against the damaging effect of oxygen radical species.