Death of cerebellar granule neurons induced by piperine is distinct from that induced by low potassium medium.

We compared neurotoxicity of piperine and low K+ on cultured cerebellar granule neurons. As considered from lactate dehydrogenase release and 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide reduction, both piperine and shifting from high K+ (25 mM) to low K+ (5.4 mM) were cytotoxic to cerebellar granule neurons. Protein synthesis inhibitors, cycloheximide and anisomycin, and an endonuclease inhibitor, aurintricarboxylic acid, were protective against low K+-induced neuronal death whereas they were ineffective against that induced by piperine. D-alpha-tocopherol, trolox, and a spin trap 3,3,5,5-tetramethyl-1-pyrroline-1-oxide were protective against piperine neurotoxicity whereas they had no effect on that induced by low K+. These results suggest that piperine and low K+ may exert neurotoxic effects on cerebellar granule neurons through different mechanisms. Death of cerebellar granule neurons induced by piperine may be mediated by non-apoptotic mechanisms and may involve membrane lipid peroxidation and/or free radical generation.