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 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.
Koch
O
O
Departmento de Patología, Facultad de Medicina, Universidad de Buenos Aires, J. Uriburu 950, P.P. 1114 Buenos Aires, Argentina.
Farré
S
S
De Leo
M E
ME
Palozza
P
P
Palazzotti
B
B
Borrelo
S
S
Palombini
G
G
Cravero
A
A
Galeotti
T
T
D000437:Alcoholism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005526:Food, Formulated; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000187:drug effects*; D014810:Vitamin E / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000175:diagnosis*
D012333:RNA, Messenger; D014810:Vitamin E; D000431:Ethanol; D013482:Superoxide Dismutase