Neuroscience Letters 383 (2005) 295–300 Rejuvenation of antioxidant system in central nervous system of aged rats by grape seed extract Muthaiya Balu, Purushotham Sangeetha, Dayalan Haripriya, Chinnakannu Panneerselvam ∗ Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India Received 11 February 2005; received in revised form 13 April 2005; accepted 13 April 2005 Abstract Oxidative stress is considered as a major risk factor that contributes to age-related increase in lipid peroxidation and declined antioxidants in the central nervous system during aging. Grape seed extract, one of the bioflavonoid, is widely used for its medicinal properties. In the present study, we evaluated the role of grape seed extract on lipid peroxidation and antioxidant status in discrete regions of the central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I—control young rats, Group II—young rats treated with grape seed extract (100 mg/kg body weight) for 30 days, Group III—aged control rats and Group IV—aged rats supplemented with grape seed extract (100 mg/kg body weight) for 30 days. Age-associated increase in lipid peroxidation was observed in the spinal cord, cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). Activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and levels of non-enzymic antioxidants like reduced glutathione, Vitamin C and Vitamin E were found to be significantly decreased in all the brain regions studied in aged rats when compared to young rats. However, normalized lipid peroxidation and antioxidant defenses were reported in the grape seed extract-supplemented aged rats. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical-induced lipid peroxidation in the central nervous system of aged rats. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Aging; Central nervous system; Free radicals; Lipid peroxidation; Antioxidant; Grape seed extract Aging is the accumulation of changes responsible for the se- quential alterations that accompany with advancing age and the associated progressive increase in the chance of disease and death. The free radical theory of aging is one of the most popular, single mechanistic theories of aging, which discloses increased generation of free radical as the major cause of cel- lular damage. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an important role in neurode- generative disorders by oxidizing the macromolecules like proteins, DNA and lipids leading to the common final path- way for cell death [13,37]. Such free radical-mediated dam- ages are prevalent during aging which leads to age-associated diseases as like Alzheimer’s disease and Parkinson’s disease [32]. ∗ Corresponding author. Tel.: +91 44 24480767; fax: +91 44 24926709. E-mail address: biobalu@gmail.com (C. Panneerselvam). Brain is highly vulnerable to oxidative damage due to high utilization of inspired oxygen, the large amount of easily ox- idizable polyunsaturated fatty acids, the abundance of redox- active transition metal ions, and relative dearth of antioxidant defense system, etc. There are numerous endogenous antiox- idants that constitute the body’s own natural defenses and limits free radical damage in neuronal tissues [26]. The in- creased oxidative damage during aging might be due to the insufficiency of antioxidants [30]. Lipid peroxidation (LPO), a marker for oxidative damage, is associated with a progres- sive loss in membrane fluidity, reduction in membrane poten- tial, increase in membrane permeability to ions which finally leads to cellular damage [41]. Elevated levels of LPO are re- sponsible for the decreased physiological performance and increased susceptibility to disease and death [39]. Brain accessible phytochemicals potentially defend against oxidative damage during aging [6]. Polyphenols of 0304-3940/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2005.04.042