Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis

Abstract

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 an intraperitoneal injection of cerulein (50 μg/kg) administered twice in 2 h. They were equally divided into the following three groups: 0.9% isotonic solution (Group 1; control), everolimus once (Group 2), and everolimus 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: Biochemical analyses of the blood samples showed statistically significant difference in red blood cell count as well as hemoglobin, hematocrit, urea, and alanine transaminase levels among the study groups (p<0.05 in all). Everolimus proved to significantly increase red blood cell count in a dose-independent manner. Hemoglobin and hematocrit levels significantly increased only after treatment with one dose of everolimus. Urea level was significantly different between the Groups 2 and 3; however, no change was observed in both groups when compared with the control. Alanine transaminase level significantly decreased 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 the specific inhibition of inflammatory response pathways. Keywords: Pancreatitis, cerulein, everolimus, inflammation INTRODUCTIONAcute pancreatitis is a localized inflammatory condition with a high mortality rate (2.1%-9.2%) worldwide. Because of its potential to trigger systemic inflammatory response, it can cause multiple organ failure (1, 2). The common causes of acute pancreatitis are alcohol abuse or gallstone disease (60%-75% of the cases) followed by hypertriglyceridemia, hyperparathyroidism, pancreatic malignancy, endoscopic retrograde cholangiopancreatography, trauma, infectious agents (increasingly associated with HIV infection), drugs (such as tetracycline, azathioprine, ethinyl estradiol, mercaptopurine, and sulfamethoxazole), autoimmunity, abdominal trauma, ischemia, diabetes mellitus, porphyria, and heredity (3-5).Although the disease is common, the treatment of acute pancreatitis is still very limited. There are only a number of pharmacological approaches, which are mostly supportive involving adequate fluid resuscitation and oxygen supplementation, to maintain normal art...

Experimental Acute Pancreatitis-Induced Lung Injury—Prevented with “Cytoflavin®”

“…Our results are comparable with another study where in genetically modified mice lacking the ability to synthesize IL-10, the course of acute pulmonary injury due to AP was significantly more severe than that in not modified animals, while the severity of AP in both groups was similar [23]. TNF-α has cytotoxic effects on the parenchymatous target cells and it increases IL-8 synthesis; moreover, it directly damages the endothelial cells and it causes the activation of coagulative hemostasis, microvascular thrombosis; finally, it also stimulates neutrophil cell accumulation in the lungs [24,25].…”