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.

Anti-Parkinson’s Activity of Uncaria Rhynchophylla Extract on Rotenone Induced Parkinsonism Model in Male Albino Rats

“…These results were parallel to those obtained by Tamilselvam et al [43] in vitro and Zaitone et al [23] in vivo. Current results could be explained by the high lipophilic affintity of rotenone that enable it to cross blood brain barrier.…”

Elucidation of the Mechanisms through Which the Reactive Metabolite Diclofenac Acyl Glucuronide Can Mediate Toxicity

“…The pesticide rotenone is a known inducer of ROS, and exposure to rotenone results in cell death (Tamilselvam et al, 2013). We conducted ROS assays with DCF and DCF-AG to determine their ROS activity.…”

Downregulation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress

“…The development and progress of the disease mainly depends on age, and approximately 1% of the older population (Ͼ60 yr) in industrialized countries are affected by PD (41). An increasing number of studies have suggested that numerous mechanisms, including mitochondrial defects, oxidative stress, dysimmunity, heredity, and cell apoptosis, have been implicated in the pathogenesis of PD (22,24,46,48). However, the precise mechanism underlying the pathogenesis of PD remains poorly understood, hampering the development of efficient treatments for PD.…”