Estudo do efeito farmacológico da alfa, ß-amirina, uma mistura de triterpenos isolada de protium heptaphyllum, na pancreatite aguda experimental

Abstract

Triterpenes are natural compounds with anti-inflammatory and cytoprotective effects relatively non-toxic. Acute pancreatitis, an inflammation of the pancreas, may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), conditions that can lead the patient to death. In this study, a mixture of triterpenes isolated from Protium hepthaphyllum was investigated for their effects in models of acute pancreatitis. In the model of acute pancreatitis induced by L-arginine, male Wistar rats were treated with a mixture of ,β-amyrin (10, 30 and 100 mg/kg, p.o.) or with vehicle (2% Tween 80 in distilled water, 10 ml/kg) 48, 24 and 1.5 h before the administration of L-arginine (2 x 2.5 g/kg, 1 h apart) or with metilprednisolone (30 mg/kg, i.m.) 30 min before the administration of L-arginine. In cerulein-induced pancreatitis, male Swiss mice were treated with a mixture of ,β-amyrin (10, 30 and 100 mg/kg, p.o.) or with vehicle (2% Tween 80 in distilled water, 10 ml/kg) 48, 24 and 1.5 h before administration of cerulein (5 x 50 mg/kg, 1 h apart) or with thalidomide (200 mg/kg, p.o.) 1h before administration of cerulein. Animals treated with saline (0.9% NaCl) were included in both models. We analyzed the pancreatic edema, serum amylase, lipase and cytokines (TNF-, IL-6), myeloperoxidase, reactive substances to thiobarbituric acid (TBARS), histology and immunohistochemistry (TNF-, iNOS and nitrotyrosine) pancreatic. L-arginine and cerulein significantly increased pancreatic edema and serum levels of amylase, lipase, TNF- and IL-6. Histopathologic evaluation of pancreas revealed the presence of edema, neutrophil infiltration, hemorrhage, acinar vacuolization and necrosis. We observed a marked increase in the expression of TNF-, iNOS and nitrotyrosine in the evaluation by immunohistochemistry. The pre-treatment with alpha and beta-amyrin (10, 30 and 100 mg/kg, p.o.), metilprednisolone (30 mg/kg, i.m.) or thalidomide (200 mg/kg, p.o.) significantly attenuated the severity of acute pancreatitis induced by either L-arginine, and by cerulein, as evidenced by the reduction of pancreatic edema, amylase, lipase and serum cytokines, myeloperoxidase and pancreatic TBARS. Furthermore, treatment with ,β-amyrin and the reference drugs suppressed the histopathological changes and expression of cytokines and nitrotyrosine pancreatic. Together, these results indicate that the mixture of ,-amyrin reduces the severity of acute pancreatitis induced by L-arginine or cerulein acting as anti-inflammatory and antioxidant agent.