Prevention by Cystine or Methionine of Hemorrhage and Necrosis of the Liver in Rats

Abstract

Necrosis, hemorrhage and cirrhosis of the liver in rats were described by György and Goldblatt. 1 They attributed these lesions to a deficiency of a part of the vitamin B₂ complex. By modifying the diet they were later 2 able to increase the incidence of the liver injury. In the report on this work, they stated that the pathogenesis of the necrosis and cirrhosis was related to the lipotropic effect of casein. Blumberg and McCollum 3 reported the production of liver cirrhosis in rats with or without accompanying necrosis and the prevention of the cirrhosis with choline.

Daft, Sebrell and Lillie 4 described the production of liver cirrhosis in rats and its prevention by choline, methionine or casein. Lowry, Daft, Sebrell, Ashburn and Lillie 5 reported that treatment by choline or casein of rats with experimentally produced liver cirrhosis resulted in hyperplastic regeneration of liver cells and clinical improvement of the animals. In a paper describing the histology and histogenesis of this liver cirrhosis, Lillie, Ashburn, Sebrell, Daft and Lowry 6 stated that among the noteworthy features is the absence of hemorrhage and, in the earlier stages, of evident necrotic liver cells.

The composition of the diets used in these 3 laboratories is given in Table I. It will be noted that our cirrhosis-producing diet No. 545 contains a much lower percentage both of casein and of fat than the diets of György and Goldblatt 1 2 and those of Blumberg and McCollum 3 and that our diet contains cornstarch while the others contain sucrose. Diet No. 545 also contains free cystine while the others do not. In view of the classic observations of Osborne and Mendel, 7 it is apparent that the 10% casein diets are deficient in the sulfur-containing amino acids.