Protective effect of alpha-tocopherol on brain cell membrane function during cerebral cortical hypoxia in newborn...

Protective effect of alpha-tocopherol on the structure and function of brain cell membranes was investigated by measuring Na+,K(+)-ATPase activity and products of lipid peroxidation (fluorescent compounds) in brain cell membranes obtained from newborn piglets. Four groups of anesthetized, ventilated piglets were studied: five hypoxic piglets and five normoxic piglets were pretreated with free alpha-tocopherol (20 mg/kg/dose i.m.), five additional hypoxic piglets received i.m. placebo and five normoxic piglets served as control. Placebo and alpha-tocopherol were given 48 and 3 h prior to onset of hypoxia. Hypoxic hypoxia was induced and cerebral hypoxia was documented as a decrease in the ratio of phosphocreatine to inorganic phosphate (PCr/P(i)) using 31P NMR spectroscopy. PCr/P(i) decreased from baseline of 2.62 +/- 0.54 to 1.05 +/- 0.27 in alpha-tocopherol-pretreated and from 2.44 +/- 0.48 to 1.14 +/- 0.30 in the placebo-pretreated group during hypoxia. Na+,K(+)-ATPase activity was unchanged in both normoxic and hypoxic alpha-tocopherol-pretreated groups. However, in placebo-pretreated hypoxic group, Na+,K(+)-ATPase activity decreased as compared with control (44.9 +/- 9.7 vs. 61.8 +/- 5.7 mumol P(i)/mg protein/h, P < 0.005). The level of fluorescent compounds increased in placebo-pretreated but not in alpha-tocopherol-pretreated group as compared with control. During hypoxia, serum alpha-tocopherol levels were higher in alpha-tocopherol-pretreated groups as compared with placebo-pretreated hypoxic group. The present data indicates that alpha-tocopherol protects brain cell membranes in newborn piglets from lipid peroxidative damage during tissue hypoxia probably by being incorporated in cell membrane and also as circulating antioxidant.