title: Mitochondrial dependent apoptosis: ameliorative effect of flunarizine on ischemia-reperfusion of celiac artery-induced gastric lesions in the rat.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Rayat Institute of Pharmacy, Nawanshahr District, Near Railmajra, Ropar, 144533, Punjab, India. arunachalammu@gmail.com
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Muthuraman
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Ramesh
authors.forename: Ashish
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002445:Celiac Artery / Q000503:physiopathology; D016572:Cyclosporine / Q000627:therapeutic use; D005444:Flunarizine / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D009853:Omeprazole / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013270:Stomach / Q000098:blood supply* / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D000897:Anti-Ulcer Agents; D007166:Immunosuppressive Agents; D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents; D016572:Cyclosporine; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D009853:Omeprazole; D005444:Flunarizine; D002118:Calcium