The influence of tumor necrosis factor alpha on the processes of sphingomyelin cycle and lipid peroxidation in brain

: The influence of tumor necrosis factor alpha (TNF-alpha) on the processes of sphingomyelin cycle activation and intensity of peroxidation in animal brain in vivo has been studied. Alterations in activity of sphingomyelinase, a key sphingomyelin cycle enzyme and in sphingomyelin, ceramide content as well as accumulation of the products of lipid peroxidation (diene conjugates and diene ketons) were measured in the cortex, the cerebellum and the hippocampus of rats 5, 15, 30 min, 1, 2 and 5 hours after TNF-alpha intraperitoneal injection in dosage 100 mkg per animal. It is shown that 2 hours after the injection, TNF-alpha initiated an accumulation of the products of lipid peroxidation, which intensively developed in the cerebellum and the hippocampus. Sphingomyelinase activation was found in the same brain structures. At the initial stage of TNF-alpha action, an increase of lipid peroxidation products correlated with sphingomyelinase activation in the cerebellum and the hippocampus suggesting an interaction of two cell signal systems of sphingomyelin cycle and oxidative system.