Trimetazidine Increases Cell Survival and Inhibits the Activation of

Abstract

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 = 7) and AP + TMZ (n = 7) groups by an injection of 4% sodium taurocholate to the pancreatic duct. The sham (n = 6) and drug (n = 6) groups were designated as control groups. The AP + 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 + 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.

C1 [Isik, Sevil] Ordu Med Pk Hosp, Dept Gen Surg, Gaffar Okan Cad 39, TR-52100 Altinordu, Ordu, Turkey.

[Sengul, Neriman] Abant Izzet Baysal Univ, Med Fac, Gen Surg Dept, Bolu, Turkey.

[Tore, Fatma] Biruni Univ, Med Fac, Physiol Dept, Istanbul, Turkey.

[Aydin, Cemalettin] Inonu Univ, Med Fac, Gen Surg Dept, Malatya, Turkey.

[Aslan, Acelya; Ucar, Gulberk] Hacettepe Univ, Pharm Fac, Biochem Dept, Ankara, Turkey.

[Firat, Tulin; Kukner, Aysel] Abant Izzet Baysal Univ, Med Fac, Histol Embryol Dept, Bolu, Turkey.

[Bayram, Recep] Abant Izzet Baysal Univ, Med Fac, Pharmachol Dept, Bolu, Turkey.

[Demirbag, Ali Eba] Turkiye Yuksek Ihtisas Postgrad Training & Res Ho, Dept Gastroenterol Surg, Ankara, Turkey.

[Orug, Taner] Bahcesehir Univ, Med Fac, Gen Surg Dept, Istanbul, Turkey.