The effect of quercetin on cerulein-induced acute pancreatitis / Efeito da quercetina sobre a pancreatite induzida por ceruleína

OBJECTIVE: The aim of this study was to evaluate the protective and therapeutic effects of quercetin on pancreatic injury in cerulein-induced acute pancreatitis. METHOD: Thirty-two rats were randomly divided into four groups, eight per group: (CT): untreated controls, (CER) treated with cerulein, 50 µg/kg body weight; (Q+CER) pre-treatment with quercetin, 100 mg/kg body weight, followed by cerulein, 50 µg/kg; (CER+Q) post-treatment, cerulein followed by quercetin, same doses. Cerulein was divided into four doses, given at 1-hour intervals by intraperitoneal injection. Quercetin was given either 1-hour before (in pre-treatment group) or 1-hour after (in post-treatment group) cerulein. Pancreatic malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), reduced and oxidized glutathione (GSH and GSSG, respectively) were measured. Histology of the pancreas was studied. RESULTS: (1) MDA, carbonyl, MPO, TNF-a and IL-6 levels were significantly higher in CER vs CT rats. (2) MDA, carbonyl, MPO and TNF-α decreased significantly in pre-treated rats vs. CER. (3) MDA, MPO, TNF-α, IL-6 were significantly lower in post-treated rats vs. CER. (4) The reduced vs. oxidized glutathione ratio (GSH/GSSG) of was significantly lower CER vs. CT rats. (5) Pre- and post-treatment with quercetin significantly increased this ratio. (6) Pancreatic histology showed that quercetin had no significant effect on the histological image of the pâncreas CONCLUSION: These results suggest that quercetin can attenuate the severity of cerulein-induced acute pancreatitis by acting as an antioxidant and anti-inflammatory agent and combating oxidative stress. Further studies are needed to clearly explain its utility on acute pancreatitis.

OBJETIVO: O objetivo deste estudo foi avaliar os efeitos protetores e terapêuticos da quercetina na lesão pancreática da pancreatite aguda induzida por ceruleína. MÉTODO: Trinta e dois ratos foram divididos aleatoriamente em quatro grupos, oito por grupo: (CT): controles não tratados (CER) tratados com ceruleína, 50 µg/kg de peso corporal; (Q+CER) pré-tratamento com quercetina, 100 mg / kg de peso corporal, seguido de ceruleína, 50 µg/kg; (CER+Q) pós-tratamento, ceruleína seguida de quercetina, mesmas doses. A ceruleína foi dividida em quatro doses, administradas a intervalos de 1 hora por injeção intraperitoneal. A quercetina foi administrada 1 hora antes (no grupo de pré-tratamento) ou 1 hora após (no pós-tratamento) a administração de ceruleína. Foram medidos o malondialdeído pancreático (MDA), carbonilo, mieloperoxidase (MPO), fator de necrose tumoral alfa (TNF-a), interleucina-6 (IL-6), glutationa reduzida e oxidada (GSH e GSSG, respetivamente). Foi estudada a histologia do pâncreas. RESULTADOS: Os níveis de MDA, carbonila, MPO, TNF-a e IL-6 foram significativamente maiores nos ratos CER vs. CT. MDA, carbonila, MPO e TNF-α diminuíram significativamente em ratos pré-tratados versus CER. MDA, MPO, TNF-α, IL-6 também foram significativamente menores em ratos pós-tratados versus CER. A proporção reduzida de glutationa oxidada (GSH/GSSG) foi significativamente menor ratos CER vs. CT; pré e pós-tratamento com quercetina aumentaram significativamente esta proporção. A histologia pancreática mostrou que a quercetina não teve efeito morfológico significativo. CONCLUSÃO: Estes resultados sugerem que a quercetina pode atenuar a gravidade da pancreatite aguda induzida por ceruleína, atuando como agente antioxidante e anti-inflamatório e combater o estresse oxidativo. Mais estudos são necessários para explicar claramente suas utilidades na pancreatite aguda.

Laparoscopy can aggravate the severity of pancreatitis in an experimental rat model.

PURPOSE: Over the past decade, laparoscopic techniques have markedly evolved, and it has been shown that minimally invasive surgery can provide a safe, effective, and less traumatic management of various surgical diseases. Additionally, it is well known that pancreatitis itself also produced severe oxidative tissue injury by increasing levels of reactive oxygen species. This study therefore aimed to investigate the effects of pneumoperitoneum on the severity of pancreatitis in a rat model of acute pancreatitis induced by cerulein. MATERIALS AND METHODS: Thirty-five Wistar albino rats were divided into five groups with seven rats in each. Experimental pancreatitis was induced using intraperitoneal injection of cerulein. The first group received open laparotomy. Groups 2-5 were treated with 5, 10, 15, and 20 mm Hg, respectively, achieved by applying pressure and waiting for 60 minutes. After this waiting interval, all of the rats were sacrificed; blood samples were taken by intracardiac puncture for biochemical assays, and pancreatic tissue samples were taken for light microscope analysis. Histopathology was scored according to edema, granulation, polymorphonuclear leukocytes, and mononuclear cells in all groups. RESULTS: Great increases in malondialdehyde and reduced glutathione levels were seen in all of the groups in which pancreatitis was induced. In Group 2-5, more significant increases were detected than in the open laparotomy group (P<.005). In the histopathological examination, Groups 2-5 showed more inflammatory cell infiltration, edema, and granulation tissue than the open laparotomy group (P<.005). CONCLUSIONS: It is useful to remember the parameters of the medical treatment of pancreatitis. While surgical treatment is being decided, we think that the process of all kinds of surgery, including laparoscopic surgery, can increase the severity of pancreatitis.

Laparoscopic preconditioning protects against oxidative injury in cerulein-induced pancreatitis rats (an experimental study).

BACKGROUND: Laparoscopic cholecystectomy, particularly in the same hospital stay, has been widely recommended to treat gallstone-pancreatitis over the last decade. Although pancreatitis produces severe oxidative injury, laparoscopy exerts an additional effect over that is produced by pancreatitis. The preconditioning phenomenon previously reported as protective in open surgery is a beneficial maneuver also in laparoscopic surgery. So in the present study we have tried to find out the effect of laparoscopic preconditioning over the pancreatitis in cerulein-induced pancreatitis rats. METHODS: Acute pancreatitis was induced in 24 rats weighing between 280 and 350 g by three subcutaneous injection of 80 µg/kg of body weight cerulein. A 1-cm midline laparotomy was performed for all rats, and then they were randomly assigned to one of the following three groups (n=8 for each): Group I (control), Group II (laparoscopy), and Group III (laparoscopic preconditioning [L-Pre]). After that, a catheter was placed into the peritoneum for the creation of the pneumoperitoneum (Pp) in all the animals except the control group. The rats of Groups II and III were subjected to 60 minutes of Pp with 15 mm Hg intraabdominal pressure followed by 30 minutes of deflation. The L-Pre procedure was applied to Group III immediately before the laparoscopic procedure. Blood samples were taken for biochemical assays. Pancreas tissue samples were taken for light microscope analysis. RESULTS: The light microscopy of the pancreas tissues revealed that cerulein injection caused edema and sparse inflammatory cell infiltration mimicking the edematous pancreatitis. However, the application of laparoscopy over the pancreatitis produced significant inflammatory cell infiltration, acinus vacuolization, and necrosis (in one case) in addition to edema. But, the laparoscopic preconditioning maneuver applied before the laparoscopy significantly decreased in particular acinary vacuolization and cell infiltration. Therefore the total sum of the histopathological score of the L-Pre group was significantly less than that of the laparoscopy group. The biochemical analysis of the groups revealed that laparoscopy caused significant elevation of malondialdehyde levels and decrease of reduced glutathione values. However, the addition of preceding preconditioning produced significant amelioration of these parameters. CONCLUSION: Laparoscopic preconditioning may be a useful method to decrease the oxidative injury in cases undergoing cholecystectomy for biliary pancreatitis. But, it should be emphasized that this was a restricted experimental study, and further clinical studies are needed to adopt these results into clinical settings.