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.
Unchern
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S
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, Japan.
Saito
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H
Nishiyama
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N
D000470:Alkaloids; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D052117:Benzodioxoles; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D002839:Chromans / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D016166:Free Radical Scavengers; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology* / Q000633:toxicity; D053284:Polyunsaturated Alkamides; D011188:Potassium / Q000008:administration & dosage*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D014810:Vitamin E / Q000494:pharmacology
D000470:Alkaloids; D052117:Benzodioxoles; D002839:Chromans; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011500:Protein Synthesis Inhibitors; D013113:Spin Labels; C051831:3,3,5,5-tetramethyl-1-pyrroline N-oxide; D014810:Vitamin E; D001312:Aurintricarboxylic Acid; D000841:Anisomycin; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase; D011188:Potassium; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C008922:piperine