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Mitochondrial Dependent Apoptosis: Ameliorative Effect of Flunarizine on Ischemia–Reperfusion of Celiac Artery-Induced Gastric Lesions in the Rat

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Abstract

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 reperfusion-induced 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 anti-oxidative, calcium regulation along with its anti-apoptotic effect.

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Acknowledgments

Thanks to all the faculty members of Rayat Institute of Pharmacy for their encouragement and support for this study.

Conflict of interest

There is no conflict of interest.

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Author notes

  1. Arunachalam Muthuraman

    Present address: Department of Pharmceutical Science & Drug Research, Pharmacology Division, Punjabi University, Patiala, 147002, Punjab, India

Authors and Affiliations

  1. Rayat Institute of Pharmacy, Nawanshahr District, Near Railmajra, Ropar, 144533, Punjab, India

    Arunachalam Muthuraman & Ashish Chauhan

  2. National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India

    Muthusamy Ramesh

  3. Lovely Professional University, Jalandhar, Punjab, India

    Ashish Chauhan

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  1. Arunachalam Muthuraman
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Correspondence to Arunachalam Muthuraman.

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Muthuraman, A., Ramesh, M. & Chauhan, A. Mitochondrial Dependent Apoptosis: Ameliorative Effect of Flunarizine on Ischemia–Reperfusion of Celiac Artery-Induced Gastric Lesions in the Rat. Dig Dis Sci 56, 2244–2251 (2011). https://doi.org/10.1007/s10620-011-1607-0

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