Mitochondrial Dependent Apoptosis: Ameliorative Effect of Flunarizine on Ischemia–Reperfusion of Celiac Artery-Induced Gastric Lesions in the Rat
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Arunachalam Muthuraman Muthusamy Ramesh Ashish Chauhan
- چاپ و سال / کشور: 2011
Description
Objectives Ischemia–reperfusion is a major event for induction of cellular apoptosis. Apoptosis is due to the activation of death receptor and/or mitochondrial pathways. Mitochondrial permeability transition pore opening is the cause of apoptosis. In our present study, we tried to evaluate the role of flunarizine in ischemia and reperfusion of celiac artery-induced gastric lesion in the rat. Methods The therapeutic potential of flunarizine was assessed by measuring the changes in gastric lesion index, biomarker (i.e., thiobarbituric acid reactive substance, reduced glutathione, superoxide dismutase,myeloperoxidase, and total calcium and protein content), and mitochondrial damage (i.e., adenosine triphosphate and deoxyribonucleic acid fragmentation content) in ischemia and reperfusioninduced gastric lesion model. Results Medium and higher doses of flunarizine produced a significant (P\0.05) ameliorative effect which was observed from the assessment of all the above-mentioned parameters (i.e., increase in reduced glutathione, superoxide dismutase and decrease in thiobarbituric acid reactive substance, myeloperoxidase, and total calcium content). Similar results were also obtained from omeprazole and cyclosporine. In the pre-treated group, deoxyribonucleic acid fragmentation pattern has also indicated that a mitochondria- associated anti-apoptotic effect of flunarizine was responsible to prevent the ischemia and reperfusion of celiac artery-induced gastric lesion. Conclusion The gastroprotective effect of flunarizine may be produced due to its inactivation potential of mitochondrial permeability transition pore opening associated with antioxidative, calcium regulation along with its anti-apoptotic effect
Dig Dis Sci (2011) 56:2244–2251 DOI 10.1007/s10620-011-1607-0 Received: 17 November 2010 / Accepted: 29 January 2011 / Published online: 16 February 2011
