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.
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.
Authors: M Rugge; M de Boni; G Pennelli; M de Bona; L Giacomelli; M Fassan; D Basso; M Plebani; D Y Graham Journal: Aliment Pharmacol Ther Date: 2010-02-23 Impact factor: 8.171
Authors: Katharinne Ingrid Moraes de Carvalho; Flavia Bonamin; Raquel Cássia Dos Santos; Larissa Lucena Périco; Fernando Pereira Beserra; Damião Pergentino de Sousa; José Maria Barbosa Filho; Lucia Regina Machado da Rocha; Clelia Akiko Hiruma-Lima Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2013-12-17 Impact factor: 3.000
Authors: Márcia Fernanda Correia Jardim Paz; Marcus Vinícius Oliveira Barros de Alencar; Rodrigo Maciel Paulino de Lima; André Luiz Pinho Sobral; Glauto Tuquarre Melo do Nascimento; Cristiane Amaral Dos Reis; Maria do Perpetuo Socorro de Sousa Coêlho; Maria Luísa Lima Barreto do Nascimento; Antonio Luiz Gomes Júnior; Kátia da Conceição Machado; Ag-Anne Pereira Melo de Menezes; Rosália Maria Torres de Lima; José Williams Gomes de Oliveira Filho; Ana Carolina Soares Dias; Antonielly Campinho Dos Reis; Ana Maria Oliveira Ferreira da Mata; Sônia Alves Machado; Carlos Dimas de Carvalho Sousa; Felipe Cavalcanti Carneiro da Silva; Muhammad Torequl Islam; João Marcelo de Castro E Sousa; Ana Amélia de Carvalho Melo Cavalcante Journal: Oxid Med Cell Longev Date: 2020-03-28 Impact factor: 6.543