Inhibitory Effects of Different Barbiturates on Lipid Peroxidation in Brain Tissue in Vitro

Abstract

The protective effect of barbiturates in cerebral ischemia has been proposed to be related to inhibition of lipid peroxidation. The present in-vitro study was undertaken to test the efficiencies of different barbiturates to inhibit peroxidative reactions in brain tissue, and to compare their effects with established free radical scavengers (chlorpromazine and promethazine). Cortical homogenates, prepared from decapitated rats, were incubated at 37 C with 5 per cent O2 (in N2) in the presence of ferrous sulfate (0.01 mM) and ascorbic acid (0.25 mM). During incubation there was extensive lipid peroxidation in the tissue, as evidenced by appreciable production of thiobarbituric acid-reactive material (TBAR), 1.2 μmol malondialdehyde g−1 cortex in one hour. Thiopental (1.0 mM) caused a 96 per cent inhibition of TBAR production, while other barbiturates (in the same concentrations) had only small (methohexital) or no (pentobarbital and phenobarbital) inhibitory effect. The inhibition of TBAR production by 1.0 mM thiopental was similar to that found with 1.0 mM chlorpromazine or 0.1 mM promethazine. The inhibitory effect of thiopental on lipid peroxidation was confirmed by analysis of fatty acids and phospholipids. Thiopental prevented the peroxidative degradation of polyenoic (20:4, 22:6) fatty acids and of ethanolamine phosphoglyceride that otherwise occurred during incubation. The marked differences between the tested barbiturates with respect to their abilities to inhibit lipid peroxidation in vitro are at variance with the fact that all of these barbiturates have been reported to protect the ischemic brain in various situations in vivo. The results imply that the protective effect of barbiturates under such conditions is unrelated to inhibition of lipid peroxidation, and suggest that instead they may act by other mechanisms.