title: Protective effect of 2-deoxy-D-glucose on the cytotoxicity of cyclosporin A in vitro.
abstract: The present study aimed to investigate the mechanism underlying the protective effect of 2-deoxy-D-glucose (2-DG) on the cytotoxicity of cyclosporin A (CsA) in vitro using NRK-52E cells. Staining with Hoechst 33342/propidium iodide prior to flow cytometric analysis was performed to assess the rate of cellular apoptosis and necrosis induced by CsA. The expression levels of lactate dehydrogenase (LDH), caspase 3, receptor-interacting protein kinase 3 (RIP3), reactive oxygen species (ROS), glutathione (GSH) and malondialdehyde (MDA) were detected using colorimetry, ELISA, western blotting or flow cytometric analysis to determine the protective effects of 2-DG on CsA-induced cell death. The results demonstrated that 2-DG inhibited the release of LDH, the activation of caspase 3 and the generation of ROS induced by CsA, but had no effect on the expression of RIP3. Treatment with 2-DG increased the expression of GSH and decreased the expression of MDA in dose-dependent manner, and reduced the rate of the cellular apoptosis and necrosis induced by CsA. Therefore, 2-DG inhibited CsA-induced cellular apoptosis and necrosis, possibly by reducing the production of ROS. Inhibiting the activation of caspase 3 is one of the protective mechanisms of 2-DG, however, the expression of RIP3 remained unaltered following treatment with 2-DG. Whether 2-DG inhibits the CsA-induced necrosis and apoptosis by inhibiting the RIP3 signaling pathway remains to be elucidated.
authors.affiliation: Department of Pharmacy, Renmin Hospital of Qingyuan, The Fifth Affiliated Hospital of Jinan University, Qingyuan, Guangdong 511515, P.R. China.
authors.forename: Zizhang
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Department of Pharmacy, Renmin Hospital of Qingyuan, The Fifth Affiliated Hospital of Jinan University, Qingyuan, Guangdong 511515, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, School of Pharmaceutical Sciences, Sun Yat‑sen University, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Renmin Hospital of Qingyuan, The Fifth Affiliated Hospital of Jinan University, Qingyuan, Guangdong 511515, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Renmin Hospital of Qingyuan, The Fifth Affiliated Hospital of Jinan University, Qingyuan, Guangdong 511515, P.R. China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Pharmacy, Renmin Hospital of Qingyuan, The Fifth Affiliated Hospital of Jinan University, Qingyuan, Guangdong 511515, P.R. China.
authors.forename: Xiangmao
authors.initials: X
authors.lastname: Lai
authors.affiliation: Department of Pharmacy, Renmin Hospital of Qingyuan, The Fifth Affiliated Hospital of Jinan University, Qingyuan, Guangdong 511515, P.R. China.
authors.forename: Chengyin
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Pharmacy, Renmin Hospital of Qingyuan, The Fifth Affiliated Hospital of Jinan University, Qingyuan, Guangdong 511515, P.R. China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Pharmacy, Renmin Hospital of Yichang, First College of Clinical Medicine, China Three Gorges University, Yichang, Hubei 443003, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis; D002460:Cell Line; D003124:Colorimetry; D016572:Cyclosporine / Q000633:toxicity*; D003847:Deoxyglucose / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008315:Malondialdehyde / Q000032:analysis; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000032:analysis
chemical_list: D020011:Protective Agents; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D016572:Cyclosporine; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat; D053148:Caspase 3; D005978:Glutathione