Effects of Everolimus on A Rat Model of Cerulein-Induced Experimental Acute Pancreatitis
Alper Bilal Özkardeş1, Birkan Bozkurt1, Ersin Gürkan Dumlu1, Mehmet Tokaç1, Aylin Kılıç Yazgan2, Merve Ergin3, Özcan Erel3, Mehmet Kılıç4
1Clinic of General Surgery, Atatürk Training and Research Hospital, Ankara, Turkey
2Clinic of Pathology, Atatürk Training and Research Hospital, Ankara, Turkey
3Department of Biochemistry, Yıldırım Beyazıt University Faculty of Medicine, Ankara, Turkey
4Department of General Surgery, Yıldırım Beyazıt University Faculty of Medicine, Ankara, Turkey
Objective: To analyze the biochemical and histopathological effects of everolimus in an experimental rat model of cerulein-induced acute pancreatitis. The aim of the present study was to determine the effects of everolimus on blood biochemical parameters and tissue histopathology in an experimental rat model of cerulein-induced acute pancreatitis.
Material and Methods: In 30 Wistar-Albino rats (male, 240–260 g), acute pancreatitis was induced by intraperitoneal injection of cerulein (50 μg/kg) twice in two hours. They were divided equally in three groups: 0.9% isotonic solution (Group 1, control), everolimus once (Group 2), or twice (Group 3) by oral gavage after cerulein injection. Thirty hours after the induction of pancreatitis, blood samples were collected by direct intracardiac puncture, rats were sacrificed, and pancreatic tissue samples were obtained.
Results: The biochemical analyses of the blood samples showed statistically significant difference in red blood cell count, hemoglobin, hematocrit, and urea and alanine transaminase between study groups (p<0.05 in all). Everolimus proved to significantly increase red blood cell count in dose independent manner. Hemoglobin and hematocrit significantly increased only after one dose of everolimus treatment. Urea showed significant difference between Groups 2 and 3, where no change observed in both groups compared to the control. Alanine transaminase decreased significantly only after treatment with two doses of everolimus. Histopathological analyses revealed that everolimus significantly decreased inflammation and perivascular infiltrate in a dose dependent manner (35% in Group 2, 75% in Group 3; p=0.048).
Conclusion: Treatment with two doses of everolimus improved some biochemical and histopathological parameters of experimental rat models of cerulein-induced acute pancreatitis and implied specific inhibition of inflammation response pathways.
Keywords: Pancreatitis, cerulen, everolimus, inflammation
Ethics committee approval was received for this study from the ethics committee of Ankara Training and Research Hospital Ethics Committee for Animal Experiments.
Concept - A.B.Ö., E.G.D., B.B.; Design - A.B.Ö., B.B.; Supervision - M.K., Ö.E.; Funding - B.B., E.G.D.; Materials - A.K.Y., M.E.; Data Collection and/or Processing - M.T., E.G.D.; Analysis and/or Interpretation -A.B.Ö., B.B.; Literature Review - A.B.Ö., E.G.D., M.T.; Writer - A.B.Ö.; Critical Review - Ö.E., M.K.
No conflict of interest was declared by the authors.
The authors declared that this study has received no financial support.