PROTECTIVE EFFECT OF ANTIOXIDANTS ON 3-NITROPROPIONIC ACID INDUCED OXIDATIVE STRESS AND COGNITIVE IMPAIRMENT

3-Nitropropionic acid (3-NP), a complex II inhibitor of the electron transport chain, causes neurotoxicity. Systemic administration of 3-NP causes motor and cognitive deficits which are associated with excessive free radical generation. Recently, curcumin and Carvedilol have been implicated as a neuroprotectant in the treatment of various neurological disorders. The present study was designed to investigate effects of curcumin and Carvedilol, on 3-NP-induced cognitive impairment and oxidative stress in rats. Acute administration of 3-NP (40 mg/kg, i.p.) showed decrease in locomotor activity and poor retention of memory in Morris water maze and elevated plus-maze task paradigms. Treatment with curcumin (20 and 40 mg/kg, p.o.) and Carvedilol (2.5 and 5 mg/kg, p.o.) once daily for a period of 5 days beginning 4 days prior to 3-NP administration significantly improved the 3-NP- impaired locomotor activity and memory. Biochemical analysis revealed that systemic 3-NP administration significantly increased lipid peroxidation and depleted reduced glutathione (GSH) levels and reduced succinate dehydrogenase (SDH) activity in the brains of rats. However pretreatment with curcumin and Carvedilol significantly attenuated 3-NP induced oxidative stress and restored the decreased SDH activity. The results of the present study clearly indicate that curcumin and Carvedilol by their antioxidant activity showed protection against 3-NP-induced cognitive impairment and associated oxidative stress.