%0 Journal Article
%T Neuroprotective Effects of Hesperidin, a Plant Flavanone, on Rotenone-Induced Oxidative Stress and Apoptosis in a Cellular Model for Parkinson¡¯s Disease
%A Kuppusamy Tamilselvam
%A Nady Braidy
%A Thamilarasan Manivasagam
%A Musthafa Mohamed Essa
%A Nagarajan Rajendra Prasad
%A Subburayan Karthikeyan
%A Arokyasamy Justin Thenmozhi
%A Subash Selvaraju
%A Gilles J. Guillemin
%J Oxidative Medicine and Cellular Longevity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/102741
%X 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. 1. Introduction Parkinson¡¯s disease (PD) is the second most common neurodegenerative disorder after Alzheimer¡¯s disease. It is characterised by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and subsequent depletion of dopamine in the striatum, the main projection area of the substantia nigra. Numerous studies using postmortem human tissues, animal models, and neuronal cell lines have reported the involvement of several pathological mechanisms responsible for the loss of dopaminergic neurons in PD, including elevated levels of iron, ubiquitin-proteasome system (UPS) dysfunction and impairment, altered calcium homeostasis, excitotoxicity, inflammation, oxidative stress, and release of apoptotic factors [1, 2]. Rotenone is a naturally occurring lipophilic compound exhibiting insecticide-like properties and is obtained from the roots of certain plants species (Derris and Lonchocarpus) [3]. It is one of the common neurotoxic agents used to examine the development of PD in animal models [4] and induces
%U http://www.hindawi.com/journals/omcl/2013/102741/