title: Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson's disease.
abstract: Rotenone a widely used pesticide that inhibits mitochondrial complex I has been used to investigate the pathobiology of PD both in vitro and in vivo. Studies have shown that the neurotoxicity of rotenone may be related to its ability to generate reactive oxygen species (ROS), leading to neuronal apoptosis. The current study was carried out to investigate the neuroprotective effects of hesperidin, a citrus fruit flavanol, against rotenone-induced apoptosis in human neuroblastoma SK-N-SH cells. We assessed cell death, mitochondrial membrane potential, ROS generation, ATP levels, thiobarbituric acid reactive substances, reduced glutathione (GSH) levels, and the activity of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) using well established assays. Apoptosis was determined in normal, rotenone, and hesperidin treated cells, by measuring the protein expression of cytochrome c (cyt c), caspases 3 and 9, Bax, and Bcl-2 using the standard western blotting technique. The apoptosis in rotenone-induced SK-N-SH cells was accompanied by the loss of mitochondrial membrane potential, increased ROS generation, the depletion of GSH, enhanced activities of enzymatic antioxidants, upregulation of Bax, cyt c, and caspases 3 and 9, and downregulation of Bcl-2, which were attenuated in the presence of hesperidin. Our data suggests that hesperidin exerts its neuroprotective effect against rotenone due to its antioxidant, maintenance of mitochondrial function, and antiapoptotic properties in a neuroblastoma cell line.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, College Rd, Annamalai Nagar, Chidambaram, Tamil Nadu 608002, India.
authors.forename: Kuppusamy
authors.initials: K
authors.lastname: Tamilselvam
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.forename: Thamilarasan
authors.initials: T
authors.lastname: Manivasagam
authors.forename: Musthafa Mohamed
authors.initials: MM
authors.lastname: Essa
authors.forename: Nagarajan Rajendra
authors.initials: NR
authors.lastname: Prasad
authors.forename: Subburayan
authors.initials: S
authors.lastname: Karthikeyan
authors.forename: Arokyasamy Justin
authors.initials: AJ
authors.lastname: Thenmozhi
authors.forename: Subash
authors.initials: S
authors.lastname: Selvaraju
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D012402:Rotenone; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D006569:Hesperidin; D053148:Caspase 3; D053453:Caspase 9