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Yeast in the Production of Dietary Massive Hepatic Necrosis in Rats¹

Nutritional Service of the Department of Pediatrics and the Castro-Intestinal Section of the Medical Clinic, School of Medicine, University of Pennsylvania, Philadelphia; the Institute for Medical Research, Cedars of Lebanon Hospital, and Department of Pathology, School of Medicine, University of Southern California, Los Angeles

In rats fed a semi-synthetic ration with a British brand of bakers' yeast as the sole source of protein massive hepatic necrosis occurred with great regularity (more than 90%). Substitution of an American brand of brewers' yeast for the British yeast deprived the diet of its "necrogenic" quality.

Supplements of cystine or of vitamin E were equally effective in the prevention of the dietary hepatic necrosis which develops in rats on a diet containing British yeast as the sole source of protein.

The necrogenic activity of the British yeast could not be explained by a difference in the content of the sulfur-containing amino acids (cystine, methionine) or of vitamin E in the British and American brands of yeast.

The possibility has been discussed that so-called dietary hepatic necrosis is due more to some unidentified "toxic" factors than to pure deficiency. Tocopherol and cystine may act as "detoxifying" agents.

Lesions consisting of squamous hyperplasia, hyperkeratosis, ulcers, and chronic inflammation were common in the forestomachs of rats receiving the basal yeast ration, with or without supplementation with vitamin E. Addition of cystine to the diet and, more definitely, exposure to "stress" (cold, muscular exercise), without any change in the dietary regime, brought about a reduction in the incidence of these gastric lesions.

Testicular hypoplasia was observed in animals exposed to "stress" but was uncommon in all other groups. On the other hand, the pathological changes in the forestomach occurred less commonly and were not as pronounced in the rats subjected to "stress."

Preliminary reports were given by one of us (P.G.) at the Third Conference on Biological Antioxidants in 1948 and at the Eighth Conference on Liver Injury in 1949, both conferences sponsored by the Josiah Macy, Jr., Foundation, New York (see respective Transactions).

Manuscript received 6 February 1950.