title: Protective effect of tropisetron on high glucose induced apoptosis and oxidative stress in PC12 cells: roles of JNK, P38 MAPKs, and mitochondria pathway.
abstract: Tropisetron, a selective 5-HT3 receptor (5-HT3R) antagonist, is widely used to counteract chemotherapy-induced emesis. There is growing interest concerning the beneficial effects of tropisetron on the treatment of several diseases. This study was carried out to examine effects of tropisetron on high glucose (HG) induced apoptosis in PC12 cells as a suitable culture model for studying neuronal functions. Apoptosis was induced by HG, and cells were treated with HG in the absence and presence of tropisetron for varying periods of time. The viability of PC12 cells was measured by MTT assay. The ROS (reactive oxygen species) production, lipid peroxidation (LPO) levels and total antioxidant power (TAP) were measured. The expressions of proapoptotic Bax, antiapoptotic Bcl-2, caspase-3, total and phosphorylated JNK and P38 MAPKs were also examined by western blotting. The results indicated that pretreatment with tropisetron significantly improved the viability of the cells and protected PC12 cells against HG induced apoptotic cell death. It could increase the concentrations of TAP. HG induced ROS generation, Bax expression and caspase 3 activation, were prevented by tropisetron. HG also induced activation of JNK and P38 MAPKs. The phosphorylation of these kinases was inhibited by tropisetron. It may be concluded that tropisetron treatment protects PC12 cells against HG-induced apoptosis by preventing JNK, P38 activation and mitochondrial pathway.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran. Azadehaminzadeh@yahoo.com.|Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Azadehaminzadeh@yahoo.com.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Aminzadeh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D007211:Indoles; D012702:Serotonin Antagonists; D000077526:Tropisetron; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: Apoptosis; Neurotoxicity; Oxidative stress; Tropisetron