Influence of vitamin E and selenium on glutathione-dependent protection against microsomal lipid peroxidation.

A GSH-dependent microsomal protein which inhibits lipid peroxidation has been described [R. F. Burk, Biochim. biophys. Acta 757, 21 (1983)]. Studies of its mechanism indicate that it scavenges free radicals. Vitamin E (alpha-tocopherol) and selenium are micronutrients which protect against lipid peroxidation. The effect of nutritional deficiencies of these substances on the GSH-dependent protection against rat liver microsomal lipid peroxidation was studied to determine whether GSH, selenium and alpha-tocopherol function through separate or shared mechanisms. In the ascorbate-iron microsomal lipid peroxidation system, there is a 1-3 min lag phase before lipid peroxidation begins. The length of the lag correlated well (r = 0.87) with the microsomal alpha-tocopherol content as measured by high pressure liquid chromatography. Thus, the selenium-deficient microsomes, which had a shorter lag than controls, had a somewhat lower alpha-tocopherol content. The vitamin E-deficient microsomes, which had no detectable alpha-tocopherol, had the shortest lag, but a distinct lag was present. Addition of 0.1 mM GSH to control microsomes prolonged the lag by 270%. In selenium-deficient and vitamin E-deficient microsomes, which had shorter initial lags, GSH addition caused 345 and 280% increases respectively. This suggests that the function of the GSH-dependent protective mechanism is unimpaired in these deficiencies. Trypsin digestion of microsomes, which abolished the lag completely and destroyed the GSH-dependent protection, had no effect on microsomal alpha-tocopherol content, however. These experiments illustrate the importance of two defenses against microsomal lipid peroxidation: the GSH-dependent protein which is responsible for the existence of the lag, and alpha-tocopherol which affects the length of the lag. They suggest that these defenses function separately to prevent peroxidation of membrane polyunsaturated fatty acids. Selenium appears to affect microsomal alpha-tocopherol content but to have no other effect on the microsomal lipid peroxidation system.