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Protective effect of 2deoxyDglucose on the cytotoxicity of cyclosporin A in vitro

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The present study aimed to investigate the mechanism underlying the protective effect of 2deoxyDglucose (2DG) on the cytotoxicity of cyclosporin A (CsA) in vitro using NRK52E 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, receptorinteracting 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 2DG on CsAinduced cell death. The results demonstrated that 2DG 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 2DG increased the expression of GSH and decreased the expression of MDA in dosedependent manner, and reduced the rate of the cellular apoptosis and necrosis induced by CsA. Therefore, 2DG inhibited CsAinduced cellular apoptosis and necrosis, possibly by reducing the production of ROS. Inhibiting the activation of caspase 3 is one of the protective mechanisms of 2DG, however, the expression of RIP3 remained unaltered following treatment with 2DG. Whether 2DG inhibits the CsAinduced necrosis and apoptosis by inhibiting the RIP3 signaling pathway remains to be elucidated.
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Document Type: Research Article

Affiliations: 1: Department of Pharmacy, Renmin Hospital of Qingyuan, The Fifth Affiliated Hospital of Jinan University, Qingyuan, Guangdong 511515, P.R. China 2: Department of Pharmacy, School of Pharmaceutical Sciences, Sun Yatsen University, Guangzhou, Guangdong 510006, P.R. China 3: Department of Pharmacy, Renmin Hospital of Yichang, First College of Clinical Medicine, China Three Gorges University, Yichang, Hubei 443003, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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