ABSTRACT
OBJECTIVE: We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis. METHODS: Male Wistar rats (200-400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n=38) was observed for 72 h and analyzed by the Mantel-Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt's scale. Cytokine expression in plasma was evaluated by the multiplex method. RESULTS: Mortality at 72 h was 33% in the control group and 60% in the treatment group (p=0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p=0.015). CONCLUSIONS: Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h.
Subject(s)
Animals , Male , Rats , Vasodilator Agents/pharmacology , Pancreatitis, Acute Necrotizing/drug therapy , Diazoxide/pharmacology , Taurocholic Acid , Vasodilator Agents/administration & dosage , Cholagogues and Choleretics , Random Allocation , Rats, Wistar , Pancreatitis, Acute Necrotizing/chemically induced , Pancreatitis, Acute Necrotizing/mortality , Pancreatitis, Acute Necrotizing/pathology , Diazoxide/administration & dosage , Disease Models, AnimalABSTRACT
PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.
OBJETIVO: Investigar os efeitos da pentoxifilina (PTX) na pancreatite aguda (PA) experimental administrando a droga após a indução da doença. MÉTODOS: Cem ratos machos Wistar foram submetidos à indução da PA através da infusão de taurocolato de sódio e divididos em três grupos: Grupo Sham: sham-operated ratos, Grupo Salina: AP e solução salina, e Grupo PTX: AP e PTX. Solução salina e PTX foram administradas 1 hora após a indução da PA. Três horas após indução da PA os níveis de fator de necrose tumoral (TNF)-α no líquido peritoneal e os níveis séricos de interleucina (IL)-6 e IL-10 foram analisados pelo método de Enzima Imunoensaio (ELISA). A atividade da mieloperoxidase (MPO) foi analisada no pulmão e foram realizadas análises histológicas do pulmão e pâncreas, além do estudo da mortalidade. RESULTADOS: A administração de PTX 1 hora após a indução da PA reduziu significativamente os níveis de TNF-α peritoneal e os níveis séricos de IL-6 e IL-10 quando comparado ao grupo salina. Redução na mortalidade foi observado após o tratamento com PTX comparado ao grupo salina. CONCLUSÃO: A administração de PTX após a indução da PA diminuiu os níveis sistêmicos de citocinas pró-inflamatórias, sugerindo a possibilidade de que existe uma janela terapêutica para PTX após o início do PA.
Subject(s)
Animals , Male , Rats , Pancreatitis, Acute Necrotizing/drug therapy , Pentoxifylline/administration & dosage , Enzyme-Linked Immunosorbent Assay , /blood , /blood , Lung/chemistry , Lung/drug effects , Pancreas/drug effects , Pancreatitis, Acute Necrotizing/blood , Pancreatitis, Acute Necrotizing/pathology , Random Allocation , Rats, Wistar , Sodium Chloride/administration & dosage , Systemic Inflammatory Response Syndrome/drug therapy , Time Factors , Treatment Outcome , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/drug effectsABSTRACT
OBJETIVO: O objetivo deste estudo é avaliar os efeitos da hipertermia na pancreatite aguda (PA) grave experimental induzida por ácido taurocólico. MÉTODO: A PA grave foi induzida pela injeção retrógrada de ácido taurocólico a 2,5 por cento ou 5 por cento no ducto pancreático principal. Após a indução, os animais foram colocados numa gaiola contendo duas lâmpadas de 100 W. A temperatura corporal foi aumentada para 39,5°C e mantida neste nível por 45 minutos. Foram estudados taxa de mortalidade em 72 horas, permeabilidade vascular no pâncreas, porcentagem de água no tecido pancreático, amilase sérica, histologia (edema, necrose acinar e infiltrado inflamatório) e níveis séricos de IL-6 e IL-10. RESULTADOS: Não houve alteração em nenhum dos parâmetros avaliados. CONCLUSÃO: Não há benefício da hipertermia na PA grave experimental induzida por ácido taurocólico.
OBJECTIVE: The aim of this study is to evaluate the effects of hyperthermia post-treatment on taurocholate-induced severe acute pancreatitis (AP) in rats. METHOD: Severe AP was induced by retrograde injection of 2,5 percent or 5 percent taurocholate solution into the main pancreatic duct. After the AP induction, animals were heated in a cage with two 100 W lamps. Body temperature was increased to 39°C and maintained at that level for 45 minutes. 72-hours mortality rate, amylase serum levels, histology (edema, acinar necrosis and inflammatory infiltrate), vascular permeability, pancreatic water content and serum levels of IL-6 and IL-1 were determinated. RESULTS: Hyperthermia post-treatment on severe AP showed no evidence of alteration in all evaluated parameters. CONCLUSION: The findings suggest no beneficial effect of the thermal stress on inflammatoy edema and mortality rate in taurocholate AP model.