SELECTIVE CYTOTOXICITY OF PIPERINE ON CULTURED RAT HIPPOCAMPAL-NEURONS IN COMPARISON WITH CULTURED ASTROCYTES - THE POSSIBLE INVOLVEMENT OFLIPID-PEROXIDATION

The present study investigated the selective cytotoxicity of piperine on cultured brain cells by using lactate dehydrogenase release, 3-(4,5 -dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium reduction, and protein content assay. Exposure to piperine induced marked injuries on cultur ed hippocampal neurons whereas it induced only a marginal toxicity on cultured astrocytes. The mechanism of cytotoxicity in hippocampal neur ons was studied by pharmacological methods. The membrane-permeable fre e radical scavengers, D-alpha-tocopherol and trolox, protected neurons from piperine toxicity whereas membrane-impermeable agents, superoxid e dismutase and catalase, were ineffective. A lipoxygenase inhibitor, mordihydroguaiaretic acid, but not a cyclo-oxygenase inhibitor, indome thacin, attenuated piperine toxicity. We provide the first evidence th at piperine induces selective neurotoxicity in vito. Although the exac t mechanism is still unclear, pharmacological evidence indicates the p ossible involvement of lipid peroxidation and the generation of free r adicals, at least partly, through an arachidonate-lipoxygenase pathway .