ARSENIC INDUCED TOXIC EFFECTS ON OXIDATIVE SYSTEM AND MRNA EXPRESSION LEVELS OF GPX IN ALBINO RAT BRAIN: PROTECTIVE EFFECT OF VITAMIN-E.

Induction of reactive oxygen species by arsenic and subsequent depletion of antioxidant cell defense can result in disruption of the pro oxidant / antioxidant balance in mammalian tissues. Therefore the brain is very susceptible to oxidative stress due to its high oxygen consumption. In the present study the young albino rats (3 months) were exposed to low dose of As (2.5 mg/kg body weight) and high dose of As (5 mg/kg body weight) through intraperitoneal injection daily for a period of 3 weeks. After the period of dosage, the As exposed animals were divided into two groups of which one group of both the doses were given Vit E at a dose of 5 mg/kg bw for a period of one week. Then the oxidative stress enzymes i.e. isoforms of Superoxide dismutase (Mn SOD & Cu/Zn-SOD), Glutathione peroxidase (GPx) and Lipid peroxidase (Lpx) were assayed. In this study, it was observed that the Mn-SOD, Cu/Zn-SOD, Glutathione peroxidase (GPx) were decreased significantly in high and low dose of As exposure in different brain regions (cerebral cortex, cerebellum and hippocampus), suggesting that As leads to alteration in the activity of antioxidant enzymes. Decrease in antioxidant enzymes were more evident in high dose compared to low dose. In this study, we have also observed that the Lpx was increased in As supplemented rats as compared to control rats. As-induced neurotoxicity is dose dependent. From our observation, it was clear that the exposure of Vitamin-E provides a protective role against toxic influence of As on high and low doses in all examined parameters in rat brain regions. In addition to this, we have also examined the mRNA expression levels of GPx in cerebral cortex of rats. The GPx expression levels were significantly decreased in As-exposed rats (both in low-high dose). The effect was more pronounced in high dose of As exposed animals. However, supplementation with Vit-E significantly reversed the As-induced decrease in gene expression levels of Gpx. The recovery in expression was more evident in low dose when compared to high dose of As exposed animals. Our results showed that the nutritional antioxidant Vit-E ameliorated oxidative stress and loss of cellular antioxidants and suggested that Vit-E efficiently protects cerebral cortex and cerebellum from arsenic induced oxidative damage. This protection may includ