740 XI. VITAMINS E (tocopherols) 



ness of DL-tocopheryl acetate in protecting carotene and vitamin A (as 

 determined by weight gains)/-' wliich has been confirmed/^'^'^-^ would also 

 suggest that the antioxygenic action of tocopherol takes place within or 

 near the alimentary tract rather than in the liAer as was suggested by 

 Popper e^ a//'^4 



Although a-, /3-, and 7-tocopherols were first reported to be equally 

 effective in protecting vitamin A/^^ the later studies of Stern et al.,^ 

 which also included 5-tocopherol, demonstrated that the antioxidant 

 potency of the tocopherols in protecting vitamin A or carotene was, in 

 order of potency : 8, 7-, /?-, and a- (proceeding from the strongest to the 

 weakest). The order of effectiveness of the tocopherols as antioxidants, as 

 demonstrated by Olcott and Emerson, ^^ was 7-, /?-, a-tocopherol (in the 

 ratio of 4.3 : 1.7 : 1). Hove and Hove,^^^ who used a different experimental 

 method, found that at low temperatures the three compounds had ap- 

 proximately equal antioxidant activity, while at high temperatures 7- 

 tocopherol was several times more active than the jS- and a-forms (5.10:2.- 

 63:1). Dam and co-workers^^^-''" showed that, in addition to vitamin E, 

 methylene blue, thionine, thiodiphenjdamine, and Antabuse (tetraethyl- 

 thiuram disulfide) caused increased deposition of vitamin A in the livers of 

 chicks and rats when "vitamin E was deficient. Howe\'er, when cod liver 

 oil was replaced by lard, or when fat was omitted from the diet, methylene 

 blue was found to have no effect upon the storage of vitamin A. For a 

 further discussion, the reader is referred to the following section. 



d. The Vitamin E-Like Action of Methylene Blue and of Related 

 Antioxidants, (a) Protection against Resorption Gestation. A number of 

 non-tocopherol antioxidants have been shown to produce a vitamin E-like 

 action when tested by the classical method employed for vitamin E, but 

 the results are somewhat inconsistent. Thus, Dam and Granados^^^ 

 reported that methylene blue improved the reproductive capacity of female 

 rats, raised on vitamin E-deficient diets which were "fat-free" or which 

 contained cod liver oil, to about the same extent as did vitamin E. These 

 investigators are of the opinion that methylene blue acts in the same 

 manner as vitamin E to maintain the integrity of certain enzymatic redox 



«3 M. C. Miles, E. M. Erickson, and H. A. Mattill, Proc. Soc. Exptl. Biol. Med., 70, 

 162-165(1949). 



"* H. Popper, F. Steigmann, and H. A. Dyniewicz, Gastro-enterology, 10, 987-1000 

 (1948). 



«6 E. L. Hove and Z. Hove, /. Biol. Chem., 156, 611-621, 623-632 (1944). 



^26 H. Dam, I. Prange, and E. S0ndergaard, Experientia, 7, 184-185 (1951). 



^27 H. Dam, I. Prange, and E. S0ndergaard, Acta Pharmacol. Toxicol., 8, 1-22, 23-29 

 (1952). 



*28 H. Dam and H. Granadoa, Acta Pharmacol. Toxicol., 8, 47-54 (1952). 



J 



