Acta Pharm. 58 (2008) 421-428
Original research paper
Protective role of the calcium channel blocker amlodipine against mitochondrial injury in ischemia and reperfusion injury of rat liver
CHATTOPADHYAY PRONOBESH, AHER VAIBHAV DAGAGI, CHAUDHURY PALLAB and WAHI ARUN KUMAR
Cellular and Microbiology Laboratory, College of Pharmacy, IFTM, Moradabad-244001, India
Birla Institute of Technology and Sciences, Pilani, India
National Biotechnology Center, Indian Veterinary Research Institute, Izatnagar, India
Accepted September 5, 2008
Ca2+ accumulation and Ca2+ overloading in mitochondria are responsible for the cell abnormality associated with ischemia and reperfusion injury. The present study was aimed at evaluating the efficacy of the Ca2+ channel blocker amlodipine on the mitochondrial Ca2+ accumulation, mitochondrial antioxidant status and mitochondrial respiratory enzymes in ischemia and reperfusion (I/R) induced liver injury. I/R injury induced mitochondrial damage in rats was assessed in terms of the decrease in activities (p < 0.05) of respiratory marker enzymes (malate dehydrogenase, succinate dehydrogenase and NADH –dehydrogenase), mitochondrial antioxidant enzymes (glutathione, superoxide dismutase, catalase), and significant increase (p < 0.05) in the level of lipid peroxidation (LPO) and Ca2+ content.
Mitochondrial damage was confirmed by transmission electron microscopic (TEM) examination. Pretreatment with amlodipine effectively counteracted the alteration in mitochondrial enzymes induced by ischemia-reperfusion liver damage. TEM study confirms the restoration of cellular normalcy and the cytoprotective role of amlodipine against I/R induced hepatic injury. On the basis of our findings it may be concluded that amlodipine not only possesses Ca2+ channel antagonist properties but it may also reduce the extent of mitochondrial damage by its antioxidant activity.
Keywords: calcium channel blocker, amlodipine, ischemic and reperfusion injury, mitochondrial injury