title: Modulatory effects of resveratrol on endoplasmic reticulum stress-associated apoptosis and oxido-inflammatory markers in a rat model of rotenone-induced Parkinson's disease.
abstract: The mechanisms leading to neuronal death in Parkinson's disease (PD) are not fully elucidated; however, mounting evidence implicates endoplasmic reticulum (ER) stress, oxidative damage, and inflammatory changes are the crucial factors in its pathogenesis. This study was undertaken to investigate the modulatory effects of resveratrol on ER stress-mediated apoptosis, inflammatory and oxidative stress markers in a rat model of rotenone-induced PD. mRNA expression levels of ER stress markers; C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), were estimated in the rat brain using quantitative real-time PCR. Caspase-3 activity, IL-1β levels and Nuclear Factor Erythroid 2-related factor (Nrf2) DNA-binding activity were estimated by ELISA, while glutathione peroxidase and Xanthine oxidase activities, as well as protein carbonyl contents in the rat brain were evaluated spectrophotometrically. Our data revealed that Resveratrol ameliorated rotenone-induced ER stress by downregulating CHOP and GRP78 genes expression and hampered caspase-3 activity in the brain of rotenone exposed rats. It also restored redox balance as evident by suppressing Xanthine oxidase activity and protein carbonyls formation; in addition to preservation of intracellular antioxidants status via activating glutathione peroxidase and Nrf2 signaling pathway. In conclusion; our study launched promising avenues for the potential use of resveratrol as a neuroprotective therapeutic agent in Parkinson's disease.
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: hanaahibishy@hotmail.com.
authors.forename: Hanaa Hibishy
authors.initials: HH
authors.lastname: Gaballah
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Soha Said
authors.initials: SS
authors.lastname: Zakaria
authors.affiliation: Clinical Pharmacology Department, Faculty of Medicine, Menoufia University, Egypt.
authors.forename: Maha M
authors.initials: MM
authors.lastname: Elbatsh
authors.affiliation: Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Nahid M
authors.initials: NM
authors.lastname: Tahoon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D064419:Chemically-Induced Disorders; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010300:Parkinson Disease; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D012402:Rotenone; D013267:Stilbenes / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics
chemical_list: D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D013267:Stilbenes; C018551:glucose-regulated proteins; D012402:Rotenone; D051742:Transcription Factor CHOP; D053148:Caspase 3; D000077185:Resveratrol
keywords: Apoptosis; Endoplasmic reticulum stress; Parkinsonism; Resveratrol; Rotenone