VII. EFFECTS OF DEFICIENCY 537 



considered — inadequate vitamin E, early age of the animal, and .some type 

 of metabolic stress or local insult of tissues. Whether the latter relates to 

 fat peroxides or to other metabolites as well is not known. There is also 

 the (question of whether in the young organism the vascular bed is peculiarly 

 susceptible to injury by such metabolic factors, or whether the metabohc 

 factors differ qualitative!}^ or quantitatively as biochemical processes 

 mature. 



Of particular interest in this connection are the studies of Holman^^^ 

 demonstrating that a necrotizing arteritis in dogs, produced by induction 

 of renal insufficiency after prior feeding of a high fat diet, can be retarded 

 or prevented by tocopherol. Here vitamin E seems to protect against chemi- 

 cal injury resulting from the presence of abnormal lipids deposited in the 

 vascular wall. Difference of opinion exists as to whether a-tocopherol does'^'^ 

 or does not^^^ protect dogs against stilbestrol -induced thrombocytopenic 

 purpura. In rats tocopherols prevent increased capillary fragility due to 

 a-irradiation."^ 



(2) Hemolysis. Gyorgy and Rose have shown that hemoglobinuria, intra- 

 vascular hemolysis, and death occurring in alloxan-treated rats are readily 

 prevented by dietary tocopherols, although the diabetic phenomena are 

 not affected i^^" and that dialuric acid, a decomposition product of alloxan, 

 and several related compounds produce hemolysis of erythrocytes.^-^' ^-^ 

 a-Tocopherol, through its function as an antioxidant, protects the red cell 

 against this chemical injury, perhaps by counteracting a free radical or 

 peroxide formed as an intermediate of the oxidation-reduction system of 

 dialuric acid and alloxan. On the basis of these reactions they have de- 

 veloped an hemolysis test which can be applied either in vivo or in vitro 

 as a measure of the biologic activity of tocopherols and of vitamin E de- 

 pletion in the rat.^-'-- ^--^ jNlodifications of this test have demonstrated in- 

 creased tendency to hemolysis in red cells of vitamin E-deficient monkeys 

 (unpublished obser\^ations in the writer's laboratory) and in those of pre- 

 mature infants,^^^ full-term infants, and newborn rats.'-'' Although hemolysis 



"6 R. L. Holman, Proc. Soc. Exptl. Biol. Med. 66, 307 (1947); Southern Med. J. 42, 



108 (1949). 

 11' F. Skelton, E. Shute, H. G. Skinner, and R. A. Waud, Science 103, 762 (1946). 

 "8 A. J. Richtsmeier, M. Spooner, and O. O. Meyer, Proc. Soc. Exptl. Biol. Med. 65, 



298 (1947). 



119 S. R. Ames, J. G. Baxter, and J. Q. GrifHtli, Jr., Intern. Z. Vitaminjorsch. 22, 401 

 (1951). 



120 P. Gyorgy and C. S. Rose, Science 108, 716 (1948). 



121 C. S. Rose and P. Gyorgy, J. Nutrition 39, 529 (1949) ; Blood 5, 1062 (1950). 



122 P. Gyorgy and C. S. Rose, Ann. N. Y. Acad. Sci. 52, 231 (1949). 

 i22« C. S. Rose and P. Gyorgy, Am. J. Physiol. 168, 414 (1952). 



123 H. H. Gordon, and J. P. de Metry Proc. Soc. Exptl. Biol. Med. 79, 446 (1952). 



12^ P. Gjorgy, G. M. Cogan, and C. S. Rose, Am. J. Diseases Children 82, 237 (1951). 



