en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><span style="line-height:2;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><strong>Introduction</strong>: Diabetic neuropathy is a well-known complication of diabetes. Recently, hyperglycemia-induced toxicity has been confirmed to participates in multiple cellular pathways typical for neural deterioration. Nicotinamide phosphoribosyltransferase/pre-b cell colony-enhancing factor (Nampt/PBEF)/visfatin is a novel endogenous ligand that some studies have shown its neuroprotective effects on neurodegenerative disease. Therefore, we hypothesized that visfatin may prevent high glucose (HG)-induced neurotoxicity by &nbsp;inhibiting apoptosis, autophagy, and reactive oxygen species (ROS) responses properly.<br> <strong>Methods</strong>: In this study, pheochromocytoma cell line 12 (PC12) cells were exposed to both HG concentrations (50, 75, 100, 125, 150 mM) and visfatin (50, 100, 150 ng/mL) at different time -points to determine the optimum time and dose of glucose and visfatin. To investigate the effects of visfatin on HG-induced damage in the PC12 diabetic neuropathy model, we examined ROS response, apoptosis, and autophagy using ROS detection kit, flow cytometry, and real-time PCR/Western blot, respectively.<br> <strong>Results</strong>: We determined that HG concentration significantly increased the ROS level and apoptosis of diabetic PC12 cells. However, visfatin treatment significantly decreased the ROS production (P<0.05) and apoptosis of diabetic PC12 cells (P<0.0001). Beclin-1 messenger ribonucleic acid (mRNA) level (P<0.05) and light chain 3 (Lc3)-II protein level (P<0.05) showed that the autophagy pathway is impaired by HG concentrations.&nbsp;<br> <strong>Conclusion</strong>: We concluded that visfatin can sufficiently decrease neural damage caused by ROS production and apoptosis under HG-induced toxicity.</span></span></span></div> Visfatin, Diabetic neuropathy, Antioxidant, Apoptosis, Autophagy 867 878 http://bcn.iums.ac.ir/browse.php?a_code=A-10-2870-2&slc_lang=en&sid=1 Sarvin Jahanbani Sarvin@gmail.com 13700319475328460047593 0009-0009-5057-484X No Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Mehdi khaksari khaksari417@yahoo.com 13700319475328460047594 13700319475328460047594 No Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. Fatemeh Sadat Bitaraf Bitaraff@gmail.com 13700319475328460047595 13700319475328460047595 No Department of Medical Biotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Majid Rahmati Majidrahmati@hotmail.com 13700319475328460047596 13700319475328460047596 No Cancer Prevention Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. Kobra Foroughi Foroughik@gmail.com 13700319475328460047597 13700319475328460047597 No Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Asghar Shayannia a.shayannia@shmu.ac.ir 13700319475328460047598 13700319475328460047598 Yes Department of Medical Biotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.