Experimental Production of Dietary Liver Injury (Necrosis,Cirrhosis) in Rats. ∗

Abstract

Liver injury, mainly in the form of acute diffuse necrosis combined with fat infiltration, has occurred irregularly in young rats fed a diet devoid of vitamin B (casein 18%, sucrose 68, melted butter fat 8, cod liver oil 2, salt mixture 4) and supplemented with thiamine, riboflavin and pyridoxine. 1 In some of these livers there was diffuse periportal fibrosis. Rats fed the same basal diet plus yeast, or concentrated yeast extract, were free from any pathological changes in the liver. Later, the occurrence of cirrhosis of the liver on a nutritional basis and its prevention similarly by the addition of yeast to the diet were reported in rabbits 2 and in guinea pigs. 3

The unpredictable and irregular incidence of liver injury in rats has been indirectly regarded as a basis for the assumption that the proper experimental conditions for the regular production of liver injury have not been provided by the experimental technic used.

In view of the well known lipotropic activity of casein, 4 the high proportion (18%) of casein in the basal diet was considered to be possibly one important factor which might counteract other conditions that would be conducive to liver injury. Consequently, rats weighing between 100 and 250 g were put on a diet that had the following composition: casein 10%, sucrose 64, lard 20, cod liver oil 2 and salt mixture 4. This modified basal diet was supplemented with thiamine, riboflavin, pyridoxine and pantothenic acid. In this group of rats the incidence of liver injury rose from an irregular occurrence, as it was in the rats on the original diet (with casein 18% and butter instead of lard), to a regular complication. Necrosis with or without cirrhosis and cirrhosis without necrosis were observed in rats that died between the 100th and 150th experimental days or were killed on the 150th day.