Exudative diathesis and lipid peroxidation in the chick.

The mode of action of vitamin E is still not fully understood. One hypothesis, however, is that it is a physiological antioxidant, preventing the accumulation of undesirable metabolic oxidation products in animal tissues. These products are usually supposed to be lipid peroxides, which, in the absence of vitamin E or other antioxidant, can break down to give free radicals that can react at random with sensitive cell structures. This hypothesis is supported by the observations that oxygen consumption by mitochondria and tissue homogenates is increased in the absence of vitamin E and that malonaldehyde production in incubated tissue homogenates (usually regarded as signifying that lipid peroxidation has taken place) is greater in those from vitamin Edeficient animals than in controls (Tappel & Zalkin, 1959; Zalkin, Tappel & Jordan, 1960; Bieri &Anderson, 1960; Bieri, Dam, Prange & S~ndergaard, 1961). The nature of this lipid peroxidation remains obscure, and Green, Diplock, Bunyan, Edwin & McHale (1961) have drawn attention to several anomalies that appear to make the hypothesis unacceptable in its present form. A new factor has been introduced into discussions of the antioxidant hypothesis by the discovery that selenium is an essential trace element for several species (Schwarz & Foltz, 1957) and that, in certain circumstances, whose precise nature is still under investigation, it can apparently function as a partial alternative to tocopherol and prevent some, though not all, signs of vitamin E deficiency. The effective amounts of Se are minute compared with those of vitamin E. The chemical form in which Se functions is at present unknown. However, Se is known to be incorporated into amino acids, and McConnell & Wabnitz (1957) found significant amounts in non-protein fractions of tissues. In order to account for the way in which Se resembles vitamin E in its nutritional role, several workers have tried to explain it also by the antioxidant hypothesis and have suggested that Se functions by forming an amino acid or protein that is a powerful in vivo antioxidant (Tappel, Zalkin & Knapp, 1960; Bieri, 1959; Bieri et al. 1961). Two criticisms can be made of experiments that have been claimed to demonstrate a relationship between the protective effect of vitamin E against the deficiency state in the chick (exudative diathesis, encephalomalacia or muscular dystrophy, depending on the nature of the diet) and its inhibition of tissue peroxidation (Machlin, Gordon & Meisky, 1959; Bieri et al. 1961). First, not all tissues show such a relationship (indeed, some show the opposite effect) and much emphasis is placed upon those that do, without any justification for it in terms of the pathology of the deficiency state. The second criticism, which is perhaps more important, is that, in those experiments in which tissue peroxidation has been markedly inhibited, the dietary concentrations of