The effect of chronic ethanol feeding on hepatic mitochondrial morphology and histochemically measured succinic dehydrogenase activity was assessed. Five monkeys of the species Macaca radiuta received a nutritionally adequate diet containing 50% of the calories as ethanol, while five others were pair-fed the same diet except that ethanol was isocalorically substituted by carbohydrate. Liver morphology was assessed at 12 and 24 months and at sacrifice after 40 to 48 months of ethanol feeding. The ethanol-fed animals developed mild to moderate fatty liver as did some of the controls. No necrosis or fibrosis developed. All ethanol-fed animals developed centrilobolar megamitochondria and centrilobular "shift" in histochemically assayed succinic dehydrogenase activity characteristic of animals fed ethanol for prolonged periods. These mitochondrial changes persisted throughout the 48-month test period without progressive increase in severity or accompanying pathology. It is concluded that the morphologic and histochemically assessed mitochondrial changes do not necessarily represent a progressive destructive effect of ethanol.
Morphologic and histochemical changes in mitochondria observed in experimental animals fed ethanol (1-7) and also in alcoholic patients (8-11) are interpreted as evidence that mitochondrial abnormalities are important in the pathogenesis of alcoholic hepatitis and cirrhosis (12,13). However, this interpretation has been challenged (14, 15).
To pursue this controversy further, we studied an ethanol-fed primate model which was primarily designed to determine the effect of chronic ethanol feeding on folate (16) and collagen (19) metabolism. Monkeys fed ethanol and a nutritionally adequate diet were used. Liver biopsies taken at 12 and 24 months of feeding and at sacrifice 40 to 48 months after ingesting alcohol were studied morphologically. It was reasoned that if the observed changes in mitochondrial morphology really are evidence of hepatic toxicity caused by ethanol, then they should be progressive and be associated with other pathologic changes such as hepatic necrosis and fibrosis.