A metabolic lesion in dietary necrotic liver degeneration.

Dietary necrotic liver degeneration is recognized now as a distinct disease entity; it is a deficiency of complex nature, which, so far, has been produced in rats (2, 3), mice (4), rabbits,’ and pigs (5, 6). The disease in rats is primarily characterized by acute massive necrosis of the liver which develops suddenly after an uneventful experimental period of several weeks duration. In most animals, the first attack of necrosis is fatal. Only 23 per cent of the animals dying from the disease show signs of earlier episodes of necrosis of the liver (7, 8). A detailed description and discussion of the various facets of this deficiency disease are found in the monograph on “Nutritional factors and liver diseases” (9). Three distinct dietary factors have been identified as protective against necrotic liver degeneration, namely, cystine (2, lo), vitamin E (ll), and Factor 3 (12). Any one of these three chemically different substances affords protection by itself (10). Assuming that the acute attack of massive necrosis is the end-result of a degeneration of metabolism in the hepatic parenchyma, we have investigated in vitro the metabolism of tissues of rats on diets which produce liver necrosis. Slices from livers of such animals exhibit a peculiar metabolic lesion several weeks before hepatic necrosis appears. They are incapable of maintaining normal respiratory activity in the Warburg apparatus; oxygen consumption declines after 30 to 60 minutes at initially normal rates. In the following, this metabolic lesion is described, its relation to the three factors which specifically prevent dietary liver necrosis is demonstrated, its biochemical nature is partially defined, and it is compared to other experimentally induced types of hepatic damage.