A study of the nutritional role of anti-oxidants in the diet of the rat.

The effectiveness of certain non-tocopherol anti-oxidants in preventing or delaying the appearance of signs of vitamin E deficiency in various species has been demonstrated. These deficiency syndromes include exudative diathesis (Dam, Kruse, Prange & Smdergaard, 195 I ) and encephalomalacia (Singsen, Bunnell, Kozeff, Matterson & Jungherr, 1955) in the chick, resorption-gestation in the rat (Dam & Granados, 1952), muscular dystrophy in the rat (Moore, Sharman & Ward, 1954), rabbit (Markees, 1954), calf (Blaxter, Brown, Wood & MacDonald, 1953) and lamb (Draper &Johnson, 1956) and infertility in turkeys (Jensen, Carver & McGinnis, 1956). The anti-oxidants that have been investigated most extensively are methylene blue (MB) and NNIdiphenyl-p-phenylenediamine (DPPD). Whereas it seems clear that the need for tocopherols in the diet is modified by the administration of certain synthetic anti-oxidants, the question of the nutritional dispensability of vitamin E has not been resolved by the experiments cited. The preventive action of non-tocopherol compounds on vitamin E deficiency might accrue either from a conservating effect on the small quantities of tocopherols present in the diet, gut and tissues or from replacement of tocopherols in their physiological role. In support of a specific metabolic need for tocopherols, Scott, Hill, Norris, Dobson & Nelson (1955) have found that DPPD fails to prevent exudative diathesis in chicks fed on diets essentially devoid of vitamin E, and they imply that its protective effect is due to the conservation of small amounts of tocopherols present in some experimental diets or in the body tissues. However, this syndrome is evidently of complex aetiology, and Stokstad (1957) has found that it is responsive to selenium. Nason & Lehman (1956) reported that D-cc-tocopherol specifically enhances the reduction of cytochrome C in vitro and that several other anti-oxidants, including DPPD, do not act in this way. Shull, Alfin-Slater, Deuel & Ershoff (1957) have observed that the protective effect of DPPD and other anti-oxidants against muscular dystrophy in the guinea-pig eventually disappears, and they suggest that these compounds act by conserving tissue tocopherols. The work of Christensen, Dam & Gortner (1956) indicates that the prevention of sterility in rats by MB is dependent upon the presence of small quantities of vitamin E in the diet. Our study was designed to evaluate further the efficacy of certain anti-oxidants, chiefly DPPD, in preventing and curing resorption-gestation in the female rat. In addition to its possible prophylactic effect, which might accrue from a protective