Effects of ethyl-pyruvate in the inflammatory response of lung injury in experimental acute pancreatitis in rats

INTRODUCTION: Severe acute pancreatitis (AP) is characterized by hemodynamic alterations and systemic inflammatory response leading to a high mortality rate. In AP the inappropriate activation of pancreatic enzymes plays an important role in pancreas autodigestion and in the inflammatory mechanisms responsible for the systemic response of the disease. Ethyl-pyruvate, a novel antiinflammatory agent, simple derivative of endogenous metabolite, has been shown to improve survival and/or ameliorate organ dysfunction in a wide variety of preclinical models of critical illnesses, such as severe sepsis, acute respiratory distress syndrome and stroke. It was hypothesized that the EP could diminish the systemic response and acute lung injury associated to necrotizing acute pancreatitis. PURPOSE: The aim of the present study was to evaluate if the ethylpyruvate solution could reduce mortality in AP and/or diminish the acute lung injury. METHODS: 40 male rats, weighing between 270 to 330 grams were operated. An experimental model of severe AP by injection of 0,1ml/100g of 2.5% sodium taurocholate into the bilio-pancreatic duct was utilized. The rats were divided into 2 groups of 10 animals each: CT - control (treatment with 50ml/kg of Ringer’s solution, intraperitoneal) and EP (treatment with 50ml/kg of Ringer ethylpyruvate solution, intra-peritoneal), 3 hours following AP induction. After 6 hours, a new infusion of the treatment solution was performed in each group. Two hours later, the animals were killed and the pulmonary parenchyma was resected for biomolecular analysis, consisting of: interleukin, myeloperoxidase, MDA, nitric oxide, metalloproteinases and heat shock protein. In the second part of the experiment, another, 20 rats were randomly divided into EP and CT groups, in order to evaluate a survival comparison between the two groups. RESULTS: There were no significant differences in IL-1B,IL-10, MMP-9, HSP70, nitric oxide, MPO, MDA (lipidic peroxidation) concerning both groups. The levels of IL-6 were significantly diminished in the EP group. Furthermore, the MMP-2 levels were also reduced in the EP group. (p<0,05). The animals from the EP treatment groups had improved survival, when compared to control group. (p<0.05). CONCLUSIONS: The ethyl-pyruvate diminishes acute lung injury inflammatory response in acute pancreatitis and ameliorates survival when compared to control group, in the experimental model of necrotizing acute pancreatitis.INTRODUÇÃO: A pancreatite aguda necrosante é caracterizada por alterações hemodinâmicas e resposta inflamatória sistêmica. A lesão pulmonar aguda é a principal causa da alta morbi-mortalidade relacionada à afecção, sendo decorrente da cascata inflamatória sistêmica subsequente à lesão pancreática. O etil-piruvato, com seu papel fundamental no metabolismo intermediário com importante ação de redução de radicais livres e espécies reativas ao oxigênio, vem sendo utilizado em estudos científicos como agente antiinflamatório. OBJETIVO: Avaliar o efeito da solução de etil-piruvato na resposta inflamatória pulmonar e sua influência na letalidade da pancreatite aguda necrosante. MÉTODOS: Foram utilizados 40 ratos Wistar machos, com peso entre 270 e 330 gramas. A pancreatite aguda foi induzida pela injeção intraductal de taurocolato de sódio a 2,5% na dose de 0,1 ml/100g de solução. Os animais foram distribuídos em dois grupos de 10: grupo Controle - CT (tratados com solução de ringer simples - 50 mg/Kg/dose por via intraperitoneal) e grupo EP (tratados com 50 mg/Kg/dose de solução de 40mM ringer etil-piruvato, por via intraperitoneal), após 3 e 6 horas da indução da PA. Após 8 horas da indução, foram submetidos à eutanásia para coleta de parênquima pulmonar para análise bioquímica, composta por: interleucinas, mieloperoxidase (MPO), malondialdeído (MDA), óxido nítrico, metaloproteinases e proteínas de choque térmico. Na segunda etapa do experimento, outros 20 animais foram aleatoriamente alocados em dois grupos de 10 (CT e EP), seguindo a mesma sequência de tratamento, para análise de sobrevivência, em 10 dias. Na análise estatística, utilizou-se utilizou-se o teste t de Student com significância para p