Evaluation of the protective and therapeutic effects of extra virgin olive oil rich in phenol in experimental model of neonatal necrotizing enterocolitis by clinical disease score, inflammation, apoptosis, and oxidative stress markers.

BACKGROUND AND AIM: Necrotizing Enterocolitis (NEC) is an inflammation-associated ischemic necrosis of the intestine. To investigate the effects of extra virgin olive oil (EVOO) on inflammation, oxidative stress, apoptosis, and histological changes in NEC-induced newborn rats. MATERIALS AND METHODS: 24 rats were randomly divided into three groups: control, NEC and NEC + EVOO. NEC induction was performed using hypoxia-hyperoxia, formula feeding, and cold stress. The NEC + EVOO group received 2 ml/kg EVOO with high phenolic content by gavage twice a day for 3 days. 3 cm of bowel including terminal ileum, cecum, and proximal colon was excised. RESULTS: Weight gain and clinical disease scores were significantly higher in the NEC + EVOO group than in the NEC group (p < 0.001). EVOO treatment caused significant decreases in IL1ß, IL6 levels (p = 0.016, p = 0.029 respectively) and EGF, MDA levels (p = 0.032, p = 0.013 respectively) compared to NEC group. Significant decreases were observed in IL6 gene expression in the NEC + EVOO group compared to the NEC group (p = 0.002). In the group NEC + EVOO, the number of Caspase-3 positive cells was found to be significantly reduced (p < 0.001) and histopathological examination revealed minimal changes and significantly lower histopathological scores (p < 0.001). CONCLUSION: Phenol-rich EVOO prevents intestinal damage caused by NEC by inhibiting inflammation, oxidative stress, apoptosis.

Long-term effects of forgotten biliary stents: a case series and literature review.

There are many studies about the biliary stents, however there is a little information about the long-term stayed forgotten biliary stents except a few case reports. We have reported the results of a number of cases with biliary stents that were forgotten or omitted by the patient and the endoscopist. During February 2010 to May 2013, five patients were referred to the general surgery clinic of Haydarpasa Numune Training and Research Hospital, Istanbul Turkey. Past history and medical documents submitted by the patient did not indicate a replacement of the biliary stent in 3 patients. Two patients knew that they had biliary stents. We also conducted a literature review via the PubMed and Google Scholar databases of English language studies published until March 2014 on forgotten biliary stent. There were 3 men and 2 women ranging in age from 22 to 68 years (mean age 41.6 years). Patients presented with pain in the upper abdomen, jaundice, fever, abnormal liver function tests or dilatation of the biliary tract alone or in combination. Patients' demographic findings are presented in Table 1. A review of three cases reported in the English medical literature also discussed. The mean duration of the patency of the stent is about 12 months. The biliary stenting is performed either with plastic or metal stents, studies recommending their replacement after 3-6 months. Patients with long stayed forgotten biliary stents are inevitably treated with surgical intervention. We recommend for all endoscopic retrograde cholangiopancreatography units provide a stent registry system that the stents placed for various therapeutic procedures are not forgotten both by the patient as well as the physician. There should be a deadline for biliary stents in the registry system for each patient.

Use of stapling devices for safe cholecystectomy in acute cholecystitis.

Many techniques are described for the ligation of a difficult cystic duct (CD). The aim of this study is to assess the effectiveness and safety of stapling of a difficult CD in acute cholecystitis using Endo-GIA. From January 2008 to June 2012, 1441 patients with cholelithiasis underwent laparoscopic cholecystectomy (LC) at the Department of General Surgery, Haydarpasa Numune Education and Research Hospital. Of these, 19 (0.62%) were identified as having a difficult CD and were ligated using an Endo-GIA stapler. All patients were successfully treated with a laparoscopic approach. The length of hospital stay was 3.4 days. There were umbilical wound infections in 4 patients (21%). The length of follow-up ranged from 1.0 to 50.4 months. In conclusion, Endo-GIA is a safe and easy treatment method for patients with a dilated and difficult CD. The cystic artery should be isolated and ligated if possible before firing the Endo-GIA stapler. If isolation and stapling are not possible, fibrin sealant can be applied to avoid bleeding. The vascular Endo-GIA can be applied in a large CD, but for acute cholecystitis with an edematous CD, the Endo-GIA roticulator 4.8 or 3.5 stapler is preferred.

Analysis of 120 patients with abdominal stab wound focusing on diagnostic role of fast.

OBJECTIVE: The purpose of this study was to evaluate the managemant results of patients with penetrating abdominal injuries. MATERIAL AND METHODS: One hundred twenty (120) patients who were admitted to the Emergency Department of Haydarpasa Numune Training and Research Hospital between December 2003 and December 2010 with abdominal stab wounds were included to retrospective study. The data of all patients regarding age, gender, FAST and CT results, injured organs, surgical procedures, length of hospital stay, follow-up were examined. USG findings were classified as follows: true positive (TP), in cases of positive USG findings, and positive laparotomy; true negative (TN), in cases of negative USG findings, and negative physical examination and follow-up findings; false negative (FN), in cases of negative USG findings, and positive laparotomy; and false positive (FP), in cases of positive USG findings, and negative physical examination and follow-up findings. Abdominopelvic CT extended from the lower chest to the symphysis pubis. CT was performed by administering radiopaque agents via intravenous (i.v.) rectal or oral route. RESULTS: One hundred twenty (120) patients who were admitted to the Emergency Department of Haydarpasa Numune Training and Research Hospital between December 2003 and December 2010 with stab abdominal injuries were hospitalized. According to USG findings, 45.7% were TP, 82.4% were TN, 10.6% were FN, and 34.3% were FP. Thirty-five patients with hemodynamic stability and positive FAST findings and 15 patients with positive hemodynamic stability but negative FAST findings underwent computed tomography. CONCLUSION: Serial FAST and CT help guide treatment for stable patients with penetrating sharp injuries to the abdomen.

Asymptomatic partial splenic infarction in laparoscopic floppy Nissen fundoplication and brief literature review.

Short gastric vessels are divided during the laparoscopic Nissen fundoplication resulting in splenic infarct in some cases. We report a case of laparoscopic floppy Nissen fundoplication with splenic infarct that was recognized during the procedure and provide a brief literature review. The patient underwent a laparoscopic floppy Nissen fundoplication. We observed a partial infarction of the spleen. She reported no pain. A follow-up computed tomography scan showed an infarct, and a 3-month abdominal ultrasound showed complete resolution. Peripheral splenic arterial branches have very little collateral circulation. When these vessels are occluded or injured, an area of infarction will occur immediately. Management strategies included a trial of conservative management and splenectomy for persistent symptoms or complications resulting from splenic infarct. In conclusion, we believe that the real incidence is probably much higher because many cases of SI may have gone undiagnosed during or following an operation, because some patients are asymptomatic. We propose to check spleen carefully for the possibility of splenic infarct.

An unusual presentation of perforated appendicitis in epigastric region.

INTRODUCTION: Atypical presentations of appendix have been reported including backache, left lower quadrant pain and groin pain from a strangulated femoral hernia containing the appendix. We report a case presenting an epigastric pain that was diagnosed after computed tomography as a perforated appendicitis on intestinal malrotation. PRESENTATION OF CASE: A 27-year-old man was admitted with a three-day history of epigastric pain. Physical examination revealed tenderness and defense on palpation of epigastric region. There was a left subcostal incision with the history of diaphragmatic hernia repair when the patient was 3 days old. He had an intestinal malrotation with the cecum fixed at the epigastric region and the inflamed appendix extending beside the left lobe of liver. DISCUSSION: While appendicitis is the most common abdominal disease requiring surgical intervention seen in the emergency room setting, intestinal malrotation is relatively uncommon. When patients with asymptomatic undiagnosed gastrointestinal malrotation clinically present with abdominal pain, accurate diagnosis and definitive therapy may be delayed, possibly increasing the risk of morbidity and mortality. CONCLUSION: Atypical presentations of acute appendicitis should be kept in mind in patients with abdominal pain in emergency room especially in patients with previous childhood operation for diaphragmatic hernia.

Antioxidant and anti-inflammatory effects of curcumin against hepatorenal oxidative injury in an experimental sepsis model in rats.

BACKGROUND: To investigate the effects of curcumin, an antioxidant and anti-inflammatory agent, on free oxygen radicals and lipid peroxidation in an experimental sepsis model, as well as to determine the role of curcumin in preventing hepatorenal tissue damage caused by sepsis. METHODS: The rats were randomly divided into three groups (n=8) as follows: control group (group 1); sepsis group (group 2); and sepsis + curcumin group (group 3). Sepsis was created using the cecal ligation and perforation (CLP) method. Curcumin was administered intraperitoneally (200 mg/kg) in two equal doses just after the perforation and at twelve hours post-perforation. RESULTS: Serum TNF-a and IL-1ß, and tissue MDA and MPO values were higher, whereas tissue GSH and Na+/K+-ATPase values were lower, in group 2 as compared to group 1. These values in group 3 were the inverse of those in group 2. As compared to group 1, histopathological evaluation of group 2 showed damaged hepatocytes, glomeruli, and tubules, whereas the damage was significantly reduced in group 3 as compared to group 2. CONCLUSION: The strong antioxidant and anti-inflammatory effects of curcumin against potential hepatorenal damage were shown using an experimental sepsis model in rats.

A modified Rendezvous ERCP technique in duodenal diverticulum.

AIM: To postoperative endoscopic retrograde cholangiopancreatography (ERCP) failure, we describe a modified Rendezvous technique for an ERCP in patients operated on for common bile duct stone (CBDS) having a T-tube with retained CBDSs. METHODS: Five cases operated on for CBDSs and having retained stones with a T-tube were referred from other hospitals located in or around Istanbul city to the ERCP unit at the Haydarpasa Numune Education and Research Hospital. Under sedation anesthesia, a sterile guide-wire was inserted via the T-tube into the common bile duct (CBD) then to the papilla. A guide-wire was held by a loop snare and removed through the mouth. The guide-wire was inserted into the sphincterotome via the duodenoscope from the tip to the handle. The duodenoscope was inserted down to the duodenum with a sphincterotome and a guide-wire in the working channel. With the guidance of a guide-wire, the ERCP and sphincterotomy were successfully performed, the guide-wire was removed from the T-tube, the stones were removed and the CBD was reexamined for retained stones by contrast. RESULTS: An ERCP can be used either preoperatively or postoperatively. Although the success rate in an isolated ERCP treatment ranges from up to 87%-97%, 5%-10% of the patients require two or more ERCP treatments. If a secondary ERCP fails, the clinicians must be ready for a laparoscopic or open exploration. A duodenal diverticulum is one of the most common failures in an ERCP, especially in patients with an intradiverticular papilla. For this small group of patients, an antegrade cannulation via a T-tube can improve the success rate up to nearly 100%. CONCLUSION: The modified Rendezvous technique is a very easy method and increases the success of postoperative ERCP, especially in patients with large duodenal diverticula and with intradiverticular papilla.

Treatment of ampullary neuroendocrine tumor by endoscopic snare papillectomy.

PATIENT: Female, 45 FINAL DIAGNOSIS: Neuroendocrine tumor Symptoms: Abdominal pain Medication: - Clinical Procedure: - Specialty: Gastroenterology and Hepatology. OBJECTIVE: Unusual setting of medical care. BACKGROUND: Neuroendocrine tumor of the ampulla of Vater is extremely rare and is generally a low-grade endocrine cell tumor. The merits of radical vs. local resection remain uncertain. CASE REPORT: A 45-year-old female patient presented with abdominal pain lasting for 2 months. Papilla that was tumor-like macroscopically was seen in the second part of the duodenum in endoscopic retrograde cholangiopancreatography. Biopsy was histologically confirmed as a low-grade neuroendocrine tumor. No lymphadenopathy or visceral metastasis was found on an abdominal CT scan, In-111 octreotide scan, and EUS. The ampulla was removed by endoscopic snare papillectomy. All margins of resection were negative for tumor. CONCLUSIONS: Endoscopic snare papillectomy may be the first step in the management of neuroendocrine tumors of the ampulla of Vater in high-risk surgical candidates and selected patients such as those with a well differentiated, low-grade, small tumor without regional/ distant metastasis. However, it can also be used in younger patients who wish to avoid surgical resection.

Surgical approach to splenic hydatid cyst: single center experience.

The benefits and risks of surgery for splenic hydatid cyst (SHC) remain controversial. We aimed to share our experience about a surgical approach for SHC. Sixteen consecutive patients with SHC disease who underwent open splenectomy at our hospital between January 2006 and July 2012 were retrospectively evaluated. Data on the patients' demographic features, clinical findings, radiological and serological diagnostic methods, and surgical and medicinal treatment options were collected and used to generate descriptive profiles of diagnosis, treatment course, and outcome. The patient population was composed of 6 females and 10 males, with an age range of 18 to 79 years (mean age: 47.0 ± 18.0). Radiological examinations detected hydatid cysts in spleen alone (n = 7) or both spleen and liver (n = 9). Preoperative serological testing identified 13 of the patients as IHA positive. All except 1 patient received a 10- to 21-day preoperative course of albendazole therapy and all patients received vaccination 1 week prior to surgery. Seven patients underwent splenectomy. The remaining patients underwent splenectomy with partial cystectomy and omentopexy (n = 6), partial cystectomy and unroofing (n = 1), pericystectomy (n = 1), or pericystectomy with partial nephrectomy (n = 1). All except one patient received a 10- to 45-day postoperative course of albendazole. No patients developed serious complications or signs of recurrence during the follow-up. The clinical profile of SHC disease at our hospital includes diagnosis by radiological methods, splenectomy treatment by simple or concomitant procedures according to the patient's symptoms, cyst size, number and localization, and compression of adjacent organs, and adjunct vaccination to decrease risk of postoperative septic complications. This profile is associated with low risk of complications and high therapeutic efficacy.

Karydakis flap procedure in patients with sacrococcygeal pilonidal sinus disease: experience of a single centre in Istanbul.

BACKGROUND: The aim of this retrospective study was to evaluate the results of patients with sacrococcygeal pilonidal sinus who underwent surgery using the Karydakis technique. METHODS: Two hundred fifty-seven patients with sacrococcygeal pilonidal sinus disease were treated by the Karydakis flap procedure between December 2003 and June 2011. Patients were evaluated with respect to age, gender, preoperative symptoms, duration of preoperative symptoms, history of pilonidal sinus surgery, early postoperative complications, recurrence rates, and cosmetic satisfaction. RESULTS: There were 223 (86.8%) male and 34 (13.2%) female patients. The mean age of the patients was 27.15 ± 7.69 years. The most frequent symptom was seropurulent discharge (57.58%). Postoperative morbidity was noted in 24 patients (9.3%). The mean hospital length of stay was 3.34 ± 1.42 days. The cosmetic satisfaction rate was 91.06%. Recurrences were noted in 6 patients (2.3%). CONCLUSION: The Karydakis flap procedure is a safe treatment alternative for the surgical treatment of sacrococcygeal pilonidal sinus disease owing to the associated low complication rate, short hospital length of stay, rapid healing, and a high patient satisfaction rate.

Gastric outlet obstruction caused by focal nodular hyperplasia of the liver: A case report and literature review.

INTRODUCTION: Here, we present a case of gastric outlet obstruction due to focal nodular hyperplasia of the liver. PRESENTATION OF CASE: A 23-year-old female presented to our emergency clinic with nausea, vomiting, and abdominal pain. Endoscopy showed that the prepyloric region of the stomach was externally compressed by a lesion. Computed tomography and magnetic resonance imaging revealed a 70mm solid mass originating from the liver, extending caudally in an exophytic manner, and compressing the stomach. Laparotomy revealed an irregular and exophytic mass originating from the liver, which caused gastric outlet obstruction. The mass was resected with a 10mm safety margin. The histopathology report of the mass returned as focal nodular hyperplasia. DISCUSSION: Gastric outlet obstruction is a clinical syndrome characterized by abdominal pain, nausea, and postprandial vomiting. This clinical condition frequently develops as a result of peptic ulcer disease, pyloric stenosis, and obstruction of pylorus by foreign bodies including phytobezoars, congenital duodenal webs, malignant disorders, and various lesions externally compressing the stomach. Gastric outlet obstruction due to hepatic lesions is extremely rare; few cases have been reported. CONCLUSION: This is the first reported case of gastric outlet obstruction that developed due to focal nodular hyperplasia of the liver.

Symptom-histopathology relation in upper GI endoscopy.

OBJECTIVE: The purpose of this article is to examine the correlation between information obtained from patients before endoscopy and histopathological findings. MATERIAL AND METHODS: One thousand, five hundred and thirty-six patients underwent upper GI endoscopy between January 2011-September 2012, without distinction of age and sex were included in the study. Patients with alarm symptoms, dyspepsia, epigastric pain, gastroesophageal reflux were recorded. Tissue samples taken for histopathological examination and H. pylori screening were evaluated by Giemsa stain. The information given by the patients and histopathological findings were comparatively evaluated. RESULTS: Six hundred and twenty-four patients (40.6%) were male and 912 (59.4%) were female. Mean age was 45 years (18-90). H. pylori was positive in 416 patients with dyspepsia (58.8%), 172 patients with epigastric pain (54.4%), 52 patients with GER symptoms (28.3%) and 128 patients with alarm symptoms (50.8%). Four patients with dyspepsia (0.6%) and 20 patients with alarm symptoms (7.9%) were diagnosed with stomach cancer. CONCLUSION: The main factor should be considered as the presence of at least one of the alarm symptoms when planning an upper GI endoscopy in a patient. In the presence of at least one of the alarm symptoms, an upper GI endoscopy should be performed regardless of age. Under the age of 50 and for patients without alarm symptoms, medical treatment can be tried before performing upper GI endoscopy. Patients with GER symptoms but not diagnosed as reflux esophagitis, should be treated long-term even when symptoms decline with initial treatment.

Incarcerated abdominal wall hernia surgery: relationship between risk factors and morbidity and mortality rates (a single center emergency surgery experience).

BACKGROUND: The aim of the present study was to investigate morbidity and mortality-related risk factors in patients undergoing surgery due to incarcerated abdominal wall hernia. METHODS: The patients were grouped according to the type of hernia (inguinal, umbilical, incisional, femoral), and these groups were evaluated in terms of risk factors affecting morbidity and mortality such as age, gender, American Society of Anesthesiologists (ASA) score, type of anesthesia, concomitant diseases, and the presence of intestinal strangulation and necrosis. RESULTS: Inguinal hernia was frequent in males, whereas femoral hernia was frequent in females (p<0.001). The rate of intestinal resection due to strangulation and necrosis was found significantly higher among femoral hernias as compared to the other types of hernia (p<0.005 and p<0.001, respectively). Advanced age (≥ 65 years), concomitant disease, strangulation, necrosis, high ASA score (III-IV), time from the onset of symptoms, and time to hospital admission were found to have significant influences on morbidity and mortality. General anesthesia was found to be a risk factor for morbidity as well (p<0.05). CONCLUSION: Incarcerated abdominal wall hernias are surgical problems with high morbidity and mortality rates. Therefore, surgery should be planned under elective conditions when hernia is detected.

Protective effects of lycopene on cerulein-induced experimental acute pancreatitis in rats.

BACKGROUND: The purpose of our study was to evaluate the protective effect of the strong antioxidant and anti-inflammatory agent, lycopene, on oxidative stress in a rat model of cerulein-induced acute edematous pancreatitis. METHODS: Sprague-Dawley rats were pretreated with lycopene (50 mg/kg, i.p.) or saline 15 min before cerulein was given 20 µg/kg (i.p.) at 1-h intervals within 4 h. Twelve hours after cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and proinflammatory cytokines (TNF-α and IL-1ß). Pancreatic tissues were taken for the determination of tissue glutathione (GSH) and malondialdehyde (MDA) levels, Na(+)/K(+)-ATPase, and myeloperoxidase (MPO) activities. Tissue samples were also examined histologically. RESULTS: Acute pancreatitis caused significant decrease in tissue GSH levels and Na(+)/K(+)-ATPase activity, while pancreatic MDA levels and MPO activity were increased. Furthermore, TNF-α, IL-1ß, and amylase lipase levels were also significantly increased. On the other hand, lycopene pretreatment reserved all these biochemical indices as well as histopathologic alterations that were induced by cerulein. CONCLUSIONS: According to the results, lycopene protects the pancreatic tissues from oxidative damage induced by cerulein, and this effect possibly involves the inhibition of neutrophil infiltration and lipid peroxidation. These results suggest that high dietary intake of tomatoes may have protective effects against acute pancreatitis.

Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats.

OBJECTIVES: This study aimed to investigate the antioxidant and anti-inflammatory effects of caffeic acid phenethyl ester (CAPE) on the methotrexate (MTX)-induced hepatorenal oxidative damage in rats. METHODS: Following a single dose of methotrexate (20 mg/kg), either vehicle (MTX group) or CAPE (10 µmol/kg, MTX + CAPE group) was administered for five days. In other rats, vehicle (control group) or CAPE was injected for five days, following a single dose of saline injection. After decapitation of the rats, trunk blood was obtained, and the liver and kidney tissues were removed for histological examination and for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and sodium potassium-adenosine triphosphatase (Na(+)/K(+) -ATPase) activity. TNF-α and IL-1ß levels were measured in the blood. KEY FINDINGS: Methotrexate administration increased the tissue MDA levels, MPO activity and decreased GSH levels and Na(+)/K(+) -ATPase activity, while these alterations were reversed in the CAPE-treated MTX group. Elevated TNF-α and IL-1ß levels were also reduced with CAPE treatment. CONCLUSIONS: The results of this study revealed that CAPE, through its anti-inflammatory and antioxidant actions, alleviates methotrexate-induced oxidative damage, which suggests that CAPE may be of therapeutic benefit when used with methotrexate.

Beneficial effects of alpha lipoic acid on cerulein-induced experimental acute pancreatitis in rats.

BACKGROUND: The present study aimed to determine the effects of alpha lipoic acid (ALA) on blood and tissue biochemical parameters, as well as tissue histopathology, in an experimental rat model of cerulein-induced acute pancreatitis (AP). METHODS: Three groups consisting of eight rats each were used, as follows: Group 1, controls; Group 2, cerulein-induced pancreatitis group treated with saline; and Group 3, cerulein-induced pancreatitis group treated with ALA. AP was induced by intraperitoneal administration of cerulein (20 µg/kg) 4 times at 1-hour intervals. The animals were decapitated 12 hours after the last dose of cerulein. Blood amylase, lipase, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α levels, pancreas tissue glutathione (GSH) and malondialdehyde (MDA) levels, as well as myeloperoxidase (MPO) and Na+-K+-ATPase activity were measured. Pancreatic tissue samples were also evaluated histopathologically under a light microscope. RESULTS: While plasma amylase, lipase, IL-1ß, and TNF-α levels, and tissue MDA and MPO levels significantly increased in rats with cerulean-induced AP, tissue GSH and Na+-K+-ATPase activity significantly reduced. These changes were reversed and improved with ALA treatment. CONCLUSION: Our findings suggest that ALA may significantly reduce morbidity and mortality by preventing organ dysfunction induced by free radicals in the pancreas.

Factors affecting mortality and morbidity in emergency abdominal surgery in geriatric patients.

BACKGROUND: The purpose of the present study was to determine the factors affecting morbidity and mortality in geriatric patients undergoing abdominal surgery. METHODS: Ninety-two patients who had undergone acute abdominal surgery at >65 years of age were evaluated in terms of surgical indications, morbidity and mortality rates and the factors affecting morbidity and mortality. Forty-eight patients (52.2%) were males and 44 (47.8%) were females. The mean age was 73.32±6.37 (65-92) years. RESULTS: The most common surgical indication was acute cholecystitis (26.09%). Morbidity was established as 21 (22.82%) and mortality as 14 (15.21%), and the most common cause of mortality was mesenteric vascular occlusion. American Society of Anesthesiology (ASA) IV was noted in 90.05% of the patients admitted to intensive care, and 92.85% of the patients had mortal progression. The mean hospitalization duration was 7.94±7.13 days (median, 7 days). While older age and high ASA scores were significantly correlated with morbidity, mortality and duration of hospitalization, gender was not (p>0.05). CONCLUSION: In order to decrease the postoperative mortality rate in geriatric patients, precaution should be taken beforehand to avoid surgical complications. By carrying out elective surgery in geriatric patients, the likelihood of common causes of acute abdomen, such as acute cholecystitis and incarcerated hernia, can be reduced.

Montelukast, a selective cysteinyl leukotriene receptor 1 antagonist, reduces cerulein-induced pancreatic injury in rats.

OBJECTIVES: This study was designed to evaluate the protective effect of the cysteinyl leukotriene receptor antagonist montelukast against pancreatic injury during acute pancreatitis. METHODS: Acute pancreatitis was induced in rats by 20-µg/kg (intraperitoneal) cerulein given at 1-hour intervals within 4 hours. Montelukast was administered intraperitoneally at a dose of 10 mg/kg 15 minutes before the first cerulein injection. Six hours after the cerulein or saline injections, the animals were killed by decapitation. Blood samples were collected to analyze amylase, lipase, and the proinflammatory cytokines tumor necrosis factor α and interleukin 1ß. Pancreas tissues were taken for the determination of tissue glutathione and malondialdehyde levels and Na,K-adenosine triphosphatase and myeloperoxidase activities. The extent of tissue injury was analyzed microscopically. RESULTS: Acute pancreatitis caused significant decreases in tissue glutathione level and Na,K-adenosine triphosphatase activity, which were accompanied with significant increases in the pancreatic malondialdehyde level, myeloperoxidase activity, and plasma cytokine level. On the other hand, montelukast treatment reversed all these biochemical indices and histopathological alterations that were induced by cerulein. CONCLUSIONS: These results suggest that cysteinyl leukotrienes may be involved in the pathogenesis of acute pancreatitis and that the cysteinyl leukotriene receptor antagonist, montelukast, might be of therapeutic value for treatment of acute pancreatitis.

Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats.

Ischemia and reperfusion (I/R) injury is characterized by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. This study was designed to assess the possible protective effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1 (CysLT1), on hepatic I/R injury in rats. Wistar albino rats through clamping hepatic artery, portal vein, and bile duct, were subjected to 45 min of hepatic ischemia followed by 60 min reperfusion period. Montelukast (10 mg/kg; i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period, the rats were killed by decapitation. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and proinflammatory cytokines (TNF-alpha and IL-1beta) were determined in blood samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) and Na+, K+-ATPase activities were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Serum ALT, AST, and LDH activities were elevated in the I/R group, while this increase was significantly decreased by montelukast treatment. Hepatic GSH levels and Na+, K+-ATPase activity, significantly depressed by I/R, were elevated back to control levels in montelukast-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels, and MPO activity due to I/R injury were reduced back to control levels with montelukast treatment. Since montelukast administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that montelukast with its anti-inflammatory and antioxidant properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.