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

Abstract

Protective effect of α-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 α-tocopherol (20 mg/kg/dose i.m.), five additional hypoxic piglets received i.m. placebo and five normoxic piglets served as control. Placebo and α-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 of2.62 ± 0.54to1.05 ± 0.27 in α-tocopherol-pretreated and from2.44 ± 0.48to1.14 ± 0.30 in the placebo-pretreated group during hypoxia. Na +,K +-ATPase activity was unchanged in both normoxic and hypoxic α-tocopherol-pretreated groups. However, in placebo-pretreated hypoxic group, Na +,K +-ATPase activity decreased as compared with control(44.9 ± 9.7vs.61.8 ± 5.7 μmol P i/mg protein/h, P < 0.005). The level of fluorescent compounds increased in placebo-pretreated but not in α-tocopherol-preatreated group as compared with control. During hypoxia, serum α-tocopherol levels were higher in α-tocopherol-pretreated groups as compared with placebo-pretreated hypoxic group. The present data indicates that α-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.