742 XI. VITAMINS E (tocopherols) 



the resorption-gestation syndrome when a-tocohydroquinoiie was substi- 

 tuted for vitamin E. 



(b) Protection against Brown Pigmentation. In spite of the fact that 

 Moore et al.'^^^-'^^^ failed to demonstrate that methylene blue could sub- 

 stitute for vitamin E in rats in so far as the reproductive function is con- 

 cerned, it was found to be fully active against browai discoloration of the 

 uterus. *^^ In addition to methylene blue, thiodiphenylamine, Bind- 

 schedler's green, malachite green, leucomalachite green, and new methylene 

 blue, were also found to be potent**^" '^^^ in preventing discoloration of the 

 uterus. When rosanihne was present in the diet to the extent of 1% of the 

 diet, or methyl violet in the proportion of 0.126%, the brown discoloration 

 of the uterus was also prevented. ^'^ However, no protection against brown 

 discoloration was obtained with p-aminobenzoic acid (0.1%), or with sulfa- 

 pyridine (0.1%).'*^^ Ascorbic acid, cystine, and a group of purine deriva- 

 tives were likewise found to give negative results. ^^^ Aaes-J0rgensen, Dam, 

 and Granados*^" reported that methylene blue and Antabuse protected 

 fairly well against yelloAV-bro\\ii discoloration of the fat, and incisor 

 depigmentation. 



(c) Protection against Muscular Dystrophy. Although Dam and co- 

 workers^^^ failed to obtain any relief by means of methylene blue in the 

 treatment of muscular dystrophy in the chick, Moore and co-workers^*® 

 did report a positive effect in the case of rats, while Markees^^^ observed a 

 similar result hi rabbits, and Blaxter alone'^^ and with associates'^- noted a 

 curative effect upon muscular dystrophy in the calf. a-Tocoquinone and 

 a-tocohydroquinone have been reported to be effective in the treatment of 

 muscular dystrophy in rabbits, ^-^--^^ in the hamster, ^^^ and in calves. ^^^ 



{d) Protection against Hemolysis of Red Blood Cells. Dam and Gra- 

 nados^^' reported that methylene blue, when fed at a level of 0.126% in the 

 diet, offers complete protection against the massive liver necrosis and liver 

 hemorrhage which usually develops in animals on a low-protein, vitamin 

 E-deficient, fat-containing diet. In an earlier study from this laboratory, 

 Christensen and Dam^"*- had observed that the feeding of methylene blue 

 at a level of 0.126% in the basal diet provided a marked though not com- 

 plete protection against hemolysis of erythrocytes in a dialuric acid solu- 

 tion. The authors suggest that the action may be due to a non-specific 



^38 T. Moore, I. M. Sharman, and R. J. Ward, Biochem. ,/., 54, xvi-xvii (1953). 

 "9 T. Moore, 1. M. Sharman, and R. J. Ward, Proc. Nutr. Soc, 12, v (1953). 

 **" K. Aaes-J0rgensen, H. Dam, and H. Granados, Acta Pharmacol. Toxicol., 7, 171-180 

 (1951). 



""H. Dam and H. Granados, Ada Pharmacol. Toxicol, 7, 181-188 (1947). 

 *^2 F. Christensen and H. Dam, Acta Pharmacol. Toxicol., 7, 167-170 (1951). 



