Protective role of the calcium channel blocker amlodipine against mitochondrial injury in ischemia and reperfusion injury of rat liver.
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.
Pronobesh
Chattopadhyay
C
Cellular and Microbiology Laboratory, College of Pharmacy, Moradabad-244001, India. chatto_pronobesh@rediffmail.com
Dagagi
Aher Vaibhav
AV
Pallab
Chaudhury
C
Kumar
Wahi Arun
WA
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*
D002121:Calcium Channel Blockers; D017311:Amlodipine; D005978:Glutathione; D002118:Calcium