Pronobesh Chattopadhyay, Dagagi Aher Vaibhav, Pallab Chaudhury, Kumar Wahi Arun
Cellular and Microbiology Laboratory, College of Pharmacy, Moradabad-244001, India.
Acta Pharm. 2008 Dec;58(4):421-8. doi: 10.2478/v10007-008-0022-3.
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.
线粒体中Ca2+的积累和Ca2+超载是导致与缺血再灌注损伤相关的细胞异常的原因。本研究旨在评估Ca2+通道阻滞剂氨氯地平对缺血再灌注（I/R）诱导的肝损伤中线粒体Ca2+积累、线粒体抗氧化状态和线粒体呼吸酶的影响。通过呼吸标记酶（苹果酸脱氢酶、琥珀酸脱氢酶和NADH脱氢酶）、线粒体抗氧化酶（谷胱甘肽、超氧化物歧化酶、过氧化氢酶）活性的降低（p<0.05）以及脂质过氧化（LPO）水平和Ca2+含量的显著增加（p<0.05）来评估I/R损伤诱导的大鼠线粒体损伤。通过透射电子显微镜（TEM）检查证实了线粒体损伤。氨氯地平预处理有效地抵消了缺血再灌注肝损伤诱导的线粒体酶的改变。TEM研究证实了细胞正常状态的恢复以及氨氯地平对I/R诱导的肝损伤的细胞保护作用。根据我们的研究结果，可以得出结论，氨氯地平不仅具有Ca2+通道拮抗剂特性，还可能通过其抗氧化活性降低线粒体损伤的程度。
