Comparative study of the therapeutic potential of octreotide versus trimetazidine and their combination on acute pancreatitis in male rats

  • Sameer H. Al-Rekabi Department of Pharmacology and Therapeutics, College of Medicine, Kufa University, Iraq.
  • Hassan A. Al-Aqooli Department of Pharmacology and Therapeutics, College of Medicine, Kufa University, Iraq.
  • Muayed S. Salim Department of Pharmacology and Therapeutics, College of Medicine, Kufa University, Iraq.


Objective Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are stillvery limited. Various theories have been suggested regarding the pathophysiology of acute pancreatitis, lot of research into differentmedical treatments for the treatment of acute pancreatitis, but it is not clear what benefits each treatment has, or indeed if any medicaltreatment is beneficial apart from supportive treatment.Aim To clarify the potential therapeutic effect of octreotide, trimetazidine, and their combination in acute pancreatitis.Methods Acute pancreatitis was induced by L-arginine and treated with octreotide subcutaneously, trimetazidine intraperitoneally andcombination therapy by octreotide and trimetazidine. The rats were followed for 24 h. At the 24th hour we determined serum levels oftumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total antioxidant capacity (TAC), lipase, and amylase, and the pancreatic tissues wereanalyzed histopathologically.Results TNF-α (P < 0.001), IL-1β (P < 0.001), TAC (P < 0.001), lipase (P < 0.001), and amylase (P < 0.001) serum levels and scores ofhistopathological changes (P < 0.05) were significantly lower in combination group as compared with both octreotide and trimetazidinegroups.Conclusion Combination treatment markedly decreases biochemical and histopathological changes in acute pancreatitis, thus amelioratepancreatic injury in l-arginine induced acute pancreatitis.
share this Article by


1. Bhandari M. Role of galanin and its antagonists in experimental acute ancreatitis/Mayank Bhandari, 1972. Ph.D. Thesis. Flinders University, 2008.
2. Felderbauer P, Müller C, Bulut K, Belyaev O, Schmitz F, Uhl W, et al. Pathophysiology and treatment of acute pancreatitis: new therapeutic targets–a ray of hope? Basic Clin Pharmacol Toxicol. 2005;97:342–350.
3. Dawra R, Saluja AK. L-arginine-induced experimental acute pancreatitis. The Pancreapedia: The Exocrine Pancreas Knowledge Base.
4. Schmidt J, Rattner DW, Lewandrowski K, Compton CC, Mandavilli U, Knoefel WT, et al. A better model of acute pancreatitis for evaluating therapy. Ann Surg. 1992;215:44–56.
5. Yenicerioglu A, Cetinkaya Z, Girgin M, Ustundag B, Ozercan IH, Ayten R, et al. Effects of trimetazidine in acute pancreatitis induced by l-arginine. Can J Surg. 2013;56:175–179.
6. Almeida JL, Sampietre SN, Mendonça Coelho AM, Trindade Molan NA, Machado MC, Monteiro da Cunha JE, et al. Statin pretreatment in experimental acute pancreatitis. JOP. 2008;9:431–439.
7. Wang Y, Guo W, Li Y, Pan X, Lv W, Cui L, et al. Hypothermia induced by adenosine 5’-monophosphate attenuates injury in an l-arginine-induced acute pancreatitis rat model. J Gastroenterol Hepatol. 2014;29:742–748.
8. Yılmaz EE, Bozdağ Z, Ibiloğlu I, Arıkanoğlu Z, Yazgan ÜC, Kaplan I, et al. Therapeutic effects of ellagic acid on l-arginin induced acute pancreatitis. Acta Cir Bras. 2016;31:396–401.
9. Cikman O, Soylemez O, Ozkan OF, Kiraz HA, Sayar I, Ademoglu S, et al. Antioxidant activity of syringic acid prevents oxidative stress in L-arginine induced acute pancreatitis: an experimental study on rats. Int Surg. 2015;100:891–896.
10. Gómez-Cambronero LG, Sabater L, Pereda J, Cassinello N, Camps B, Viña J, et al. Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications. Curr Drug Targets Inflamm Allergy. 2002;1:393–403.
11. Nader MA, Wagih HM. Nilotinib, a tyrosine kinase inhibitor exhibits protection against acute pancreatitis-induced lung and liver damage in rats. Naunyn Schmiedebergs Arch Pharmacol. 2017;390:291–300.
12. Aziz NM, Kamel MY, Rifaai RA. Effects of hemin, a heme oxygenase-1 inducer in l-arginine-induced acute pancreatitis and associated lung injury in adult male albino rats. Endocr Regul. 2017;51:20–30.
13. Yang J, Sun H, Takacs P, Zhang Y, Liu J, Chang Y, et al. The effect of octreotide on hepatic ischemia-reperfusion injury in a rabbit model. Transplant Proc. 2013;45:2433–2438.
14. Zhang XP, Tian H, Lai YH, Chen L, Zhang L, Cheng QH, et al. Protective effects and mechanisms of baicalin and octreotide on renal injury of rats with severe acute pancreatitis. World J Gastroenterol. 2007;13:5079–5089.
15. Tian H, Zhang X, Wu C, Chen L, Ying R, Ye J, et al. Effects of baicalin and octreotide on the serum TNF-alpha level and apoptosis in multiple organs of rats with severe acute pancreatitis. Inflammation. 2009;32:191–201.
16. Tanoglu A, Yamanel L, Inal V, Ocal R, Comert B, Bilgi C. Appreciation of trimetazidine treatment in experimental sepsis rat model. Bratisl Lek Listy. 2015;116:124–127.
17. Tanoglu A, Yazgan Y, Kaplan M, Berber U, Kara M, Demırel D, et al. Trimetazidine significantly reduces cerulein-induced pancreatic apoptosis. Clin Res Hepatol Gastroenterol. 2015;39:145–150.
18. Vinokurov MG, Astashkin EI, Yurinskaya MM, Glezer MG, Sobolev KE, Grachev SV. Trimetazidine blocks store-operated Ca(2+) channels in HL-60 and THP-1cell lines and inhibits the secretion of tumor necrosis factor. Dokl Biol Sci. 2011;441:417–420.
19. Wang J, Sun Z, Shen J, Wu D, Liu F, Yang R, et al. Octreotide protects the mouse retina against ischemic reperfusion injury through regulation of antioxidation and activation of NF-κB. Oxid Med Cell Longev. 2015;2015:970156.
20. Kara H, Karatas F, Tug T, Canatan H, Karaoglu A. Protective effect of octreotide on intra-tracheal bleomycin-induced oxidative damage in rats. Exp Toxicol Pathol. 2010;62:235–241.
21. Chen A, Li W, Chen X, Shen Y, Dai W, Dong Q, et al. Trimetazidine attenuates pressure overload-induced early cardiac energy dysfunction via regulation of neuropeptide Y system in a rat model of abdominal aortic constriction. BMC Cardiovasc Disord. 2016; 16: 225.
22. Mahfoudh-Boussaid A, Zaouali MA, Hauet T, Hadj-Ayed K, Miled AH, Ghoul-Mazgar S, et al. Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment. J Biomed Sci. 2012;19:71.
23. Hassanzadeh G, Hosseini A, Pasbakhsh P, Akbari M, Ghaffarpour M, Takzare N, et al. Trimetazidine prevents oxidative changes induced in a rat model of sporadic type of Alzheimer’s disease. Acta Med Iran. 2015;53:17–24.
24. Chen CC, Wang SS, Lee FY, Tsay SH, Wu SL, Lu RH, et al. Prophylactic octreotide reduces the severity of histopathologic changes and hemodynamic shock in early taurodeoxycholate-induced experimental pancreatitis. Proc Natl Sci Counc Repub China B. 1999;23:1–6.
25. Woeste G, Wullstein C, Meyer S, Usadel KH, Hopt UT, Bechstein WO, et al. Octreotide attenuates impaired microcirculation in postischemic pancreatitis when administered before induction of ischemia. Transplantation. 2008;86:961–967.
26. Kafali ME, Gul M, Alptekin H, Sahin M, Toy H, Akoz M. Is there a relationship between beginning time and efficiency of octreotide in the treatment of experimental acute pancreatitis? J Korean Surg Soc. 2012;82:296–301.
27. Zhou MT, Chen BC, Sun HW, Jin YP, Yang FJ, Zhang X, et al. Continuous regional arterial infusion with fluorouracil and octreotide attenuates severe acute pancreatitis in a canine model. PLoS One. 2012;7:e37347.
28. Zhang XP, Zhang L, Yang P, Zhang RP, Cheng QH. Protective effects of baicalin and octreotide on multiple organ injury in severe acute pancreatitis. Dig Dis Sci. 2008;53:581–591.
29. Zhang XP, Tian H, Wu DJ, Feng GH, Chen L, Zhang J, et al. Pathological changes in multiple organs of rats with severe acute pancreatitis treated by baicalin and octreotide. Hepatobiliary Pancreat Dis Int. 2009;8:85–92.
30. Güler O, Akturan S, Kisli E, Dolapçi I, Caydere M, Akova A. Acute pancreatitis, bacterial translocation, and different octreotide regimens: an experimental study. Surg Today. 2009;39:876–883.
How to Cite
AL-REKABI, Sameer H.; AL-AQOOLI, Hassan A.; SALIM, Muayed S.. Comparative study of the therapeutic potential of octreotide versus trimetazidine and their combination on acute pancreatitis in male rats. Journal of Contemporary Medical Sciences, [S.l.], v. 4, n. 4, dec. 2018. ISSN 2413-0516. Available at: <>. Date accessed: 17 jan. 2019.