Trimetazidine increases cell survival and inhibits the activation of inflammatory response in sodium taurocholate–induced acute pancreatitis


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Isik S., Sengül N., Töre F., Aydın C., Aslan A., Uçar G., ...More

International Surgery, vol.102, no.11-12, pp.542-551, 2017 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 102 Issue: 11-12
  • Publication Date: 2017
  • Doi Number: 10.9738/intsurg-d-17-00122.1
  • Journal Name: International Surgery
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.542-551
  • Keywords: Acute pancreatitis, Mitochondria, Trimetazidine, Mast cell, Oxidative stress, Experimental

Abstract

© 2017 Isik et al.Objective: To evaluate the therapeutic effects of trimetazidine (TMZ) in an experimental acute pancreatitis (AP) model induced with sodium taurocholate (STC). Summary of Background Data: At present, AP is considered a disease with no specific treatment. Preventing mitochondrial dysfunction in acinar cells may be an option for specific treatment of AP. TMZ is an anti-ischemic drug with anti-inflammatory, antioxidant, and mitochondrial modulatory effects. Methods: Rats were divided into 4 groups. AP was induced in the AP (n ¼ 7) and AP þ TMZ (n ¼ 7) groups by an injection of 4% sodium taurocholate to the pancreatic duct. The sham (n ¼ 6) and drug (n ¼ 6) groups were designated as control groups. The AP þ TMZ and drug groups were administered TMZ. Samples were taken at 72 hours, and histopathologic changes as well as biochemical parameters were analyzed. Results: Serum amylase, tissue myeloperoxidase activity, malondialdehyde levels, serum cytokine levels, and mast cell degranulation rates were elevated after induction of AP, whereas tissue antioxidant enzyme activities and cell viability rates [determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay] decreased. These parameters were found to be different in the AP group compared with those in all other groups (P, 0.05). A significant improvement of all parameters was achieved with the TMZ treatment of AP. Histologically, significant differences were found between the AP and AP þ TMZ groups in terms of leukocyte infiltration, necrosis, and apoptotic cell counts. Conclusions: In this study, we demonstrated that TMZ treatment protected the mitochondrial function and prevented the activation of the inflammatory cascade in the sodium taurocholate–induced AP model.