THE EFFECT OF AMLODIPINE IN AMELIORATING THE HYPOBARIC HYPOXIA INDUCED NEURONAL DAMAGES AND DYSFUNCTION

Calcium accumulation and calcium overload in the intracellular organelles has been known to be the main reason for cellular abnormalities related to oxidative stress. The study deals with the effects of an important calcium channel blocker (CCB)amlodipine in countering the hypoxia induced oxidative stress, in vitro and in vivo. We examined the intracellular calcium changes along withReactive Oxygen Species(ROS), lipid peroxidation by malondialdehyde(MDA) and reduced glutathione levels(GSH). Amlodipine displayed its maximum efficacy in attenuating oxidative damage during hypoxic insult of 0.5% hypoxia for 24 hours at concentration of 12.5nM. Amlodipine was also found effective in controlling apoptosis by maintaining Bax/Bcl-2 ratio, Cox-2 and VEGF levels significantly offering neuroprotective activity in N2a cells.In hypobaric hypoxia subjected (25,000 ft, 280mmHg and 28^ᵒC for 24 h) Sprague Dawley (S/D) rats, intracellular calcium levels were found to be lowered significantly in amlodipine treated group (10mg kg^-1 body weight) when compared to control group. Vascular leakage and brain water content were also found to be significantly decreased upon treatment with amlodipine compared to control animals. Similarly, antioxidant status significantly improved in brain and was evaluated using ROS, MDA and GSH levels. These results suggest a protective role of amlodipine against oxidative damage and edema formed in response to hypobaric hypoxia.