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
chatto_pronobesh@rediffmail.com
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