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FASTING RELATED AUTOPHAGY DECREASES THE SEVERITY OF ACUTE PANCREATITIS IN A RODENT MODEL OF SEVERE DISEASE
Marcel C C. Machado
*, Marcia K. Koike, Denise F. Barbeiro, Francisco G. Soriano
University of São Paulo - School of Medicine, São Paulo, Brazil
Backgrounds: Pancreatitis mainly post- operative is a severe and potentially fatal disease .Its pathogenesis is not completely understood however intra acinar trypsinogen activation has been considered the main initiating event .Autophagy is a mechanism that mediates degradation of non- essential cellular components and generates vital nutrients. In a study of effect of autophagy in acute pancreatitis it was observed that autophagy is impaired in pancreatitis resulting in acinar cell vacuolization and intra acinar trypsin accumulation. Starvation is considered a strong stimulation of the autophagy process. It is therefore conceivable that fasting induced autophagy may reduce the severity of acute pancreatitis. This concept could be applied to preoperative preparation for pancreatic procedures. The aim of this study was to evaluate the influence of different periods of fasting on the severity of the disease in a model of rodent severe acute pancreatitis.
Methods: Male Wistar rats (8-10 weeks-old) were submitted to acute pancreatitis (AP) induced by injecting 2.5% taurocholic acid into the pancreatic duct and divided into the following groups: No fasting (n = 20), Fasting 12h (n = 10), and Fasting 24h (n = 10). Water was offer ad libitum during all protocol. Collection of biological samples was performed 24-hours after surgery. Measurements of MDA, and cytokines (Il-6, IL-10, TNF-alpha) were carried out using the Elisa method and Beclin-1, marker of autophagy by quantitative PCR. Histological evaluation was made in HE stained pancreatic tissue section.
Results: It was observed a reduction in mortality, serum levels of amilase and IL-6 in 12 and 24 h fasting animals. MDA, IL-10 and TNF-alpha were similar among groups. It was also observed an increase in Beclin-1 expression in pancreatic tissue of animals with AP in the 12h and 24 h fasting groups. The degree of histological lesions was reduced in 12 and 24 fasting groups.
Conclusion: Fasting lessens the severity of acute pancreatitis by a mechanism related to increased autophagy. This finding may have implications on the preoperative preparations for pancreatic procedures.
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