540 THE TOCOPHEROLS 



form of irregular trabeculae with extensive disorganization of the paren- 

 chyma. If such diets are low in vitamin E, as was usually the case in the 

 early studies, the livers become grossly brownish-yellow in color and on 

 histologic examination show accumulations of ceroid pigment in cells of 

 the parenchyma and fibrotic areas, especially in the latter.^' ^^^- '^"^ As 

 mentioned previously (p. 516) this ceroid is generally indistinguishable 

 from the acid-fast pigment of vitamin E deficiency. Tocopherols have no 

 influence on the fatty or fibrotic changes but retard or prevent ceroid for- 

 mation.^ The cellular rections which occur in areas of fatty infiltration of 

 hepatic cells are essentially the same as those described above for adipose 

 tissue and indicate the need for tocopherols to prevent undesired oxidative 

 changes in the infiltrating lipids. Dietary unsaturated fats such as cod liver 

 oil accentuate ceroid formation. ^^^ Except for dissemination of much of this 

 pigment to the lungs, the histopathologic changes in the musculature and 

 other tissues are typical of those seen in rats fed low-E diets containing 

 adequate protein. 



A different type of liver injury, known as acute or massive hemorrhagic 

 necrosis, occurs in rats reared on diets low in vitamin E and deficient in 

 sulfur-containing amino acids (alkali-treated casein or low casein diets) ^^^""^ 

 or containing as their protein component certain yeasts (high yeast 

 diets) '^^'^'^^ which lack an unidentified protective substance (factor 3 of 

 Schwarz)'^^ present in most American yeasts. There is a vast and confusing 

 literature on this subject, which now warrants the statement of Schwarz^'*^ 

 that "a simultaneous lack of 3 factors — cystine, vit. E and factor 3 — is a 

 prerequisite for the development of dietary necrotic liver degeneration, 

 and each one of them alone can protect." It is not yet clear how each of 

 these substances acts in protecting the rat against the rather sudden onset 

 of massive necrosis and hemorrhage in the liver^^*- '^i"^^'' or massive lung 

 hemorrhages,^'"' which cause death. In addition to widespread centrolob- 

 ular necrosis of the liver, there have been noted dystrophic changes in 

 skeletal muscles, ^*^' ^^^ ulcers of the forestomach,^''^' ^*'' kidney lesions, and 

 hemorrhage in lymph nodes and intestine. ^*^ 



135 P. Gyorgy, Am. J. Clin. Pathol. 14, 67 (1944). 



"6 H. Popper, P. Gyorgy, and H. Goldblatt, Arch. Pathol. 37, 161 (1944). 



1" M. Wachstein, Proc. Sac. Exptl. Biol. Med. 59, 73 (1945). 



138 p. Gyorgy and H. Goldblatt, /. Exptl. Med. 89, 245 (1949). 



139 K. 8ohwarz, Z. phijsiol. Chem. 281, 106 (1944); 283, 106 (1948); Ann. N. Y. Acad. 

 Sci. 52, 225 (1949). 



"0 E. L. Hove, D. H. Copeland, and W. D. Salmon, J. Nutrition 39, 397 (1949). 



1^1 M. Goettsch, /. Nutrition 44, 443 (1951). 



"2 O. Lindan and H. P. Himsworth, Brit. J. Exptl. Pathol. 31, 651 (1950). 



i« P. Gyorgy, C. S. Rose, R. M. Tomarolli, and II. Goldl)latt, J. Nutrition 41, 265 



(1950). 

 1^^ K. Schwarz, Proc. Soc. Exptl. Biol. Med. 77, 818; 78, S52 (1951). 



