Caffeine augments Alprazolam induced cytotoxicity in human cell lines

详细信息    查看全文

• 作者：Biswarup Saha ; An ; a Mukherjee ; Saheli Samanta ; Piyali Saha ; Anup Kumar Ghosh ; Chitta Ranjan Santra ; Parimal Karmakar
• 关键词：Alprazolam ; Caffeine ; Cell death ; Necrosis ; Lysosomes ; μ ; -Calpain ; Cathepsin B
• 刊名：Toxicology in Vitro
• 出版年：2009
• 出版时间：September 2009
• 年：2009
• 卷：23
• 期：6
• 页码：1100-1109
• 全文大小：2268 K

文摘

Combined effects of alprazolam (Alp), a member of benzodiazepine group of drugs and caffeine on human cell lines, HeLa and THP1 were investigated in this study. Alp mediated cytotoxicity was enhanced while caffeine was present. The cell death was confirmed by observing morphological changes, LDH assay and membrane anisotropic study. Also such combined effects induced elevated level of ROS and depletion of GSH. The mechanism of cell death induced by simultaneous treatment of Alp and caffeine was associated with the calcium-mediated activation of μ-calpain, release of lysosomal protease cathepsin B, activation of PARP and cleavage of caspase 3. Our results indicate that, Alp alone induces apoptosis in human cells but in the presence of caffeine it augments necrosis in a well-regulated pathway. Thus our observations strongly suggest that, alprazolam and caffeine together produce severe cytotoxicity in human cell lines.