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 cerebella r granule neurons. As considered from lactate dehydrogenase release an d 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide reduct ion, both piperine and shifting from high K+ (25 mM) to low K+ (5.4 mM ) were cytotoxic to cerebellar granule neurons. Protein synthesis inhi bitors, cycloheximide and anisomycin, and an endonuclease inhibitor, a urintricarboxylic acid, were protective against low K+-induced neurona l death whereas they were ineffective against that induced by piperine . D-alpha-tocopherol, trolox, and a spin trap 3,3,5,5-tetramethyl-1-py rroline-1-oxide were protective against piperine neurotoxicity whereas they had no effect on that induced by low K+. These results suggest t hat piperine and low K+ may exert neurotoxic effects on cerebellar gra nule neurons through different mechanisms. Death of cerebellar granule neurons induced by piperine may be mediated by non-apoptotic mechanis ms and may involve membrane lipid peroxidation and/or free radical gen eration.