Effects of the seleno-organic substance Ebselen in two different models of acute pancreatitis.

This study evaluated the effects of the seleno-organic substance Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one] in two models of acute hemorrhagic and acute edematous pancreatitis. Ebselen is known to catalyze glutathione peroxidase-like reactions and to inhibit lipid peroxidation. Hemorrhagic pancreatitis was induced by feeding a choline-deficient, ethionine-supplemented (CDE) diet to mice for 66 h. Edematous pancreatitis was induced by 7-h subcutaneous injections of 50 micrograms/kg of cerulein in mice. Ebselen was given from the beginning of the CDE diet either as a subcutaneous injection of 100 mg/kg at 6-h intervals or was mixed in with the CDE diet to yield a daily dose of 100 mg/kg of Ebselen. In further experiments, Ebselen was given at various time intervals after the beginning of the CDE diet as subcutaneous injections of 100 mg/kg at 6-h intervals. In the cerulein model, Ebselen was given 5 min prior to each cerulein injection at doses from 10-500 mg/kg. Prophylactic administration of Ebselen given orally or subcutaneously significantly improved survival from 38.5% in the control group of saline-injected CDE-fed mice to 61.9 and 65.0%, respectively. Ebselen also reduced increases in serum amylase and pancreatic weight in the diet model. Therapeutic administration of Ebselen significantly increased survival only when injections were started 20 h after the beginning of the CDE diet (64%), but not when started after 40 h (44%). Similarly, increases in serum amylase and pancreatic weight due to the CDE diet were significantly reduced by Ebselen only when injections were started after 20 h but not when started after 40 h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation

We studied the histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation in rats. All rats received 4 subcutaneous injections of various doses of caerulein (5-50 micrograms/kg body weight) at hourly intervals over 3 h, and 9 h after the first injection all animals were killed. Subcutaneous injections of 20 micrograms/kg body weight of caerulein induced a significant increase in serum amylase activity and histologic evidence of acute interstitial pancreatitis similar to those observed with the 50 micrograms/kg body weight dosage of caerulein. Therefore, a total of 4 subcutaneous injections of 20 micrograms/kg body weight of caerulein was chosen to study the time-course of structural and biochemical alterations in caerulein-induced acute pancreatitis. Serum amylase activity reached a maximal value of 10-fold increase over the basal values at 6 h, and then decreased gradually to normal values at 18 h after the first injection. Remarkable interstitial edema and cytoplasmic vacuoles in acinar cells were the earliest histologic alterations. Cellular infiltration was prominent at 9-12 h after the first injection. Although these histologic changes almost completely disappeared after 24 h, the reduction in the number of zymogen granules was still detectable by electron microscopic examination even after 7 days. DNA content in the pancreas showed no significant changes following the induction of acute pancreatitis, whereas a moderate to marked reduction in enzyme content persisted after 7 days. Within 14 days after the initiation of the injections, both structural and biochemical changes had completely disappeared.     

胰岛β细胞参与急性胰腺炎后胰腺再生过程的研究

目的 探讨胰岛β细胞在实验性急性胰腺炎(AP)后胰腺再生过程中的作用.方法 SD大鼠87只,按数字表法随机分为对照组(15只)、糖尿病组(24只)、AP组(24只)和糖尿病+AP组(24只).采用腹腔注射链脲佐菌素(STZ,60 mg/kg体重)或左旋精氨酸(L-Arg,2.5 g/kg体重,2次)方法分别建立糖尿病和AP模型.术后1、3、5、7d分批处死大鼠.检测血淀粉酶和血糖水平;计算胰腺湿重比;胰腺组织常规病理学检查,计算胰腺坏死面积百分比和组织转化区域百分比;免疫荧光检测胰岛β细胞的再生基因( Reg4)和胰岛素的表达.结果 注射STZ后,大鼠血糖明显升高,注射L-Arg后大鼠胰腺组织水肿、坏死、炎细胞浸润,血淀粉酶明显升高,表明制模成功.制模后第3天糖尿病+ AP组的胰腺坏死面积为(71.6±6.0)％,显著大于AP组的(42.3±4.0)％;第7天的组织转化面积为(45.6±5.4)％,显著小于AP组的(78.5±6.4)％.糖尿病+AP组胰岛β细胞的Reg4和胰岛素表达均较AP组明显减少.结论 STZ破坏了胰岛β细胞,加重精氨酸诱导的AP的损伤,并抑制胰腺的再生过程.     

Beneficial effect of octreotide treatment in acute pancreatitis in rats

Summary Conclusions Octreotide treatment contributes to the regulation of tumor necrosis factor (TNF) production in sodium taurocholate-induced acute necrotizing pancreatitis in rats. Owing to its complex effect, octreotide can partially ameliorate the deleterious consequences of acute necrotizing pancreatitis. Elevated TNF and interleukin-6 (IL-6) levels in the peritoneal fluid may be considered a consequence of the activation of peritoneal macrophages. Background The effects of octreotide on exocrine pancreatic function have been investigated in numerous studies, but little attention has been paid to its influence on cytokine production in acute pancreatitis. Methods Acute pancreatitis was induced by the retrograde injection of taurocholic acid into the pancreatic duct in male Wistar rats. Serum amylase activity, wet pancreatic weight/body weight (pw/bw) ratio, and TNF and IL-6 levels were measured. Four μg/kg of octreotide was administered subcutaneously at the time of induction of pancreatitis and 24 or 48 h later. Rats were sacrificed 6, 24, 48, or 72 h after the operation. Results The serum amylase level and pancreatic weight to body weight ratio were decreased significantly in the octreotide-treated group. The serum TNF level was decreased significantly in the octreotide-treated group as compared with the control group at 6, 24, and 48 h (0.6±1.5, 2.0±3.3, and 0 vs. 50±15.5, 37.5 ±18.4, and 13.1±12.5 U/mL, respectively). The ascites TNF level was decreased to 0 in the octreotide-treated group and was elevated in the control group at 72 h (28.0±49.0 U/mL). IL-6 production in ascites was extremely high in both groups at 6 h (80,000±43, 817 pg/mL and 58, 500±33 335 pg/mL), but the difference was not significant.     

Prophylactic effect of somatostatin on post-ERCP pancreatitis: a randomized controlled trial

BACKGROUND: Somatostatin is a potent inhibitor of pancreatic secretion and has been studied for its prophylactic effect on post-ERCP pancreatitis. However, results of previous trials have been inconclusive. METHODS: A prospective double-blind controlled study was performed to evaluate the effectiveness of somatostatin in preventing post-ERCP pancreatitis. Post-ERCP enzyme elevation, abdominal pain and pancreatitis were evaluated and compared between 109 patients randomized to receive somatostatin infusion and 111 patients randomized to receive normal saline infusion (placebo); both started 30 minutes before ERCP and continued for 12 hours. RESULTS: Post-ERCP elevation of serum amylase and lipase levels at 6 and 24 hours after ERCP was less frequent in the group given somatostatin but not statistically significant. There was a tendency toward lower mean serum amylase and lipase levels at 24 hours in patients given somatostatin, although the difference was not statistically significant either. Eight patients given somatostatin (7%) and 18 patients given placebo (16%) had significant abdominal pain after ERCP requiring analgesia (p = 0.04). The frequency of clinical pancreatitis was significantly lower in patients given somatostatin (3%) than in those given placebo (10%) (p = 0.03). CONCLUSIONS: Prophylactic treatment with somatostatin reduced the frequency of post-ERCP pancreatitis.     

Effect of early antibiotic prophylaxis with ertapenem and meropenem in experimental acute pancreatitis in rats

Background

The clinical course in acute necrotizing pancreatitis is mainly influenced by bacterial infection of pancreatic and peripancreatic necrosis. The effect of two antibiotic treatments for early prophylaxis was studied in the taurocholate model of necrotizing pancreatitis in the rat.

Methods

Sixty male Sprague-Dawley rats were divided into three pancreatitis groups (15 animals each) and a sham-operated group (15 animals, control group). Pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were placed on one of two different antibiotic regimens (15 mg/kg ertapenem or 20 mg/kg meropenem, one shot) after the induction of pancreatitis or received no antibiotics (control). All animals were sacrificed after 24 h to study pancreatic and extrapancreatic infection.

Results

Early antibiotic prophylaxis with either erapenam or meropenem significantly decreased pancreatic infection from 12/15 (control group) to 4/15 (ertapenem antibiotic group) and 3/15 (meropenem antibiotic group) (P < 0.05).

Conclusions

In our animal model of necrotizing pancreatitis, early antibiotic prophylaxis with ertapenem and meropenem reduced bacterial infection of the pancreas. The efficacy of early antibiotic prophylaxis with ertapenem in the clinical setting should be subject to further research.     

Necrostatin-1对雨蛙肽诱导的小鼠急性胰腺炎的保护作用

目的观察Necrostatin-1(Nec-1)对雨蛙肽诱导的小鼠急性胰腺炎(AP)的影响。方法 C57BL/6小鼠予以50μg/kg的雨蛙肽腹腔注射7次,间隔1 h,建立AP模型。于第1次雨蛙肽注射后3 h、6 h、9 h和12 h,取出胰腺组织,HE染色。Western blot检测RIP1和RIP3蛋白的表达;C57BL/6小鼠随机分为:Control组、Vehicle组、Nec-1组和Nec-1i组,予以50μg/kg的雨蛙肽腹腔注射10次,间隔1 h,第1次雨蛙肽注射2 h前,腹腔注射Nec-1(1 mg/kg,每6 h 1次)、Nec-1i或等体积溶剂和空白对照。于第1次雨蛙肽注射后12 h、18 h和24 h,收集血清和胰腺组织。检测血清淀粉酶和脂肪酶。HE染色评估胰腺损伤程度。Real-time RT-PCR检测胰腺组织IL-1β和TNF-αmRNA的表达。结果 RIP1和RIP3蛋白在雨蛙肽诱导的AP中逐渐升高,且与胰腺腺泡细胞的坏死呈正相关;应用Nec-1后,与Vehicle组和Nec-1i组比较,于12 h、18 h和24 h,小鼠血清淀粉酶和脂肪酶水平明显降低,胰腺组织病理评分也明显减少,同时胰腺组织中IL-1β和TNF-αmRNA的水平也明显降低。结论 Nec-1对实验性胰腺炎具有明显的保护作用;程序性坏死可能促进了急性胰腺炎的损伤。     

Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation

Summary We studied the histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation in rats. All rats received 4 subcutaneous injections of various doses of caerulein (5–50 μg/kg body weight) at hourly intervals over 3 h, and 9 h after the first injection all animals were killed. Subcutaneous injections of 20 μg/kg body weight of caerulein induced a significant increase in serum amylase activity and histologic evidence of acute interstitial pancreatitis similar to those observed with the 50 μg/kg body weight dosage of caerulein. Therefore, a total of 4 subcutaneous injections of 20 μg/kg body weight of caerulein was chosen to study the time-course of structural and biochemical alterations in caerulein-induced acute pancreatitis. Serum amylase activity reached a maximal value of 10-fold increase over the basal values at 6 h, and then decreased gradually to normal values at 18 h after the first injection. Remarkable interstitial edema and cytoplasmic vacuoles in acinar cells were the earliest histologic alterations. Cellular infiltration was prominent at 9–12 h after the first injection. Although these histologic changes almost completely disappeared after 24 h, the reduction in the number of zymogen granules was still detectable by electron microscopic examination even after 7 days. DNA content in the pancreas showed no significant changes following the induction of acute pancreatitis, whereas a moderate to marked reduction in enzyme content persisted after 7 days. Within 14 days after the initiation of the injections, both structural and biochemical changes had completely disappeared. *** DIRECT SUPPORT *** A00DX035 00005     

Continuous intravenous octreotide treatment for acute experimental pancreatitis

BACKGROUND: The efficacy of octreotide, the synthetic analogue of the hormone somatostatin, for the treatment of acute pancreatitis is controversial. Octreotide has been commonly administered in subcutaneous bolus injections; however, continuous intravenous infusion may be advantageous for acute conditions. METHODS: Acute experimental pancreatitis was induced in rats by intraparenchymal injections of 1 ml 10% sodium taurocholate, and octreotide (1 microg/kg/h, dissolved in physiological solution, intravenously was started 4 h later and continuously infused for 48 h. Physiological solution infusions, in identical volumes, were used in the controls. The following parameters were examined: mortality; macroscopic and histological damage; hematocrit; plasma pH; acid-base balance; serum glucose; calcium, and amylase. RESULTS: Octreotide treatment had a striking effect on mortality: 8.3 versus 91.6% in the treatment and control groups, respectively (p < 0.001). Octreotide also ameliorated pancreatic edema and intestinal dilatation, and had significant beneficial effects on histopathological damage and the biochemical alterations which are associated with acute pancreatitis. CONCLUSIONS: Continuous intravenous octreotide infusion is a potentially efficacious therapeutic method for acute pancreatitis.     

Effect of 5-FU on modulation of disarrangement of immuneassociated cytokines in experimental acute pancreatitis

AIM： To investigate the effects of 5-Fluorouracil （5-FU） on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METHODS： Male Sprague Dawley rats were assigned to 3 Groups： Group A, sham operated rats as controls （n = 7）; Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation （n = 7）, and blood samples were taken for measurement of tumor necrosis factor-α （TNF-α）, interleukin-1 （IL-1）, interleukin-6 （IL-6） （by bioassay）, and interleukin-10 （IL-10）, transforming growth factor-β （TGF-β） （by ELISA）. The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured. RESULTS： Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines （TNF-α, IL-1, IL-6） at the 2 and 6 h period and the anti-inflammatory cytokines （IL-10, TGF-β） at 24 h increased significantly （P 〈 0.05） in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation （P 〈 0.05）, and IL-IO, TGF-13 were inhibited at 24 h compared to Group B （P 〈 0.05）. Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU. CONCLUSION： 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune o/tokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.     

New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats

We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr. The contents of pancreatic protein, DNA, and digestive enzymes were markedly reduced after the arginine injection and reached their nadirs at 72 hr. After 14 days these levels were almost normal. Histologic examination revealed a number of small vesicles within acinar cells at 6 hr, which were identified as markedly swollen mitochondria by the electron microscope. Other intracellular organelles and nuclei also showed degenerative changes. At 12 hr interstitial edema appeared, and acinar cell necrosis was seen after 24 hr. The extent and severity of necrotic changes of pancreatic exocrine tissue with inflammatory cell infiltration were maximal at 72 hr. At seven days, pancreatic acinar cells began to regenerate, and pancreatic architecture appeared almost normal after 14 days. The present study has demonstrated that the administration of excessive doses of arginine induces a new, noninvasive experimental model of acute necrotizing pancreatitis.     

Timing of enteral nutrition in acute pancreatitis: Meta-analysis of individuals using a single-arm of randomised trials

IntroductionIn acute pancreatitis, enteral nutrition (EN) reduces the rate of complications, such as infected pancreatic necrosis, organ failure, and mortality, as compared to parenteral nutrition (PN). Starting EN within 24 h of admission might further reduce complications.MethodsA literature search for trials of EN in acute pancreatitis was performed. Authors of eligible trials were requested to provide the data of all patients in the EN-arm of their trials. A meta-analysis of individual patient data was performed. The cohort of patients with EN was divided into patients receiving EN within 24 h or after 24 h of admission. Multivariable logistic regression, adjusting for predicted disease severity and trial, was used to study the effect of timing of EN on a composite endpoint of infected pancreatic necrosis, organ failure, or mortality.ResultsObservational data from 165 individuals from 8 randomised trials were obtained; 100 patients with EN within 24 h and 65 patients with EN after 24 h of admission. In the multivariable model, EN started within 24 h of admission compared to EN started after 24 h of admission, reduced the composite endpoint from 45% to 19% (adjusted odds ratio [OR] of 0.44; 95% confidence interval [CI] 0.20–0.96). Within the composite endpoint, organ failure was reduced from 42% to 16% (adjusted OR 0.42; 95% CI 0.19–0.94).ConclusionsIn this meta-analysis of observational data from individuals with acute pancreatitis, starting EN within 24 h after hospital admission, compared with after 24 h, was associated with a reduction in complications.     

Involvement of Oxygen-Derived Free Radicals in L-Arginine-Induced Acute Pancreatitis

This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 × 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 48 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800 ± 3813 vs 6382 ± 184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00 ± 1.75 vs 0.28 ± 0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 ± 2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55 ± 0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.     

The protective effect of the trypsin inhibitor urinastatin on cerulein-induced acute pancreatitis in rats

We examined the protective effects of the trypsin inhibitor, urinastatin, extracted from human urine in experimental acute pancreatitis in conscious rats. Acute pancreatitis was induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Urinastatin at a dose of 50,000 U/kg body weight/6.5 h was given by continuous i.v. infusion beginning 0.5 h before the first cerulein injection and continuing until 3 h after the last one, for a total of 6.5 h. Urinastatin significantly reduced serum levels of amylase, lipase, and anionic trypsin(ogen) but did not affect pancreatic wet weight or protein or enzyme content. Urinastatin also significantly reduced the degree of acinar cell vacuolization, interstitial edema, and cellular infiltration. These results suggest that urinastatin does not block the induction of acute pancreatitis by cerulein but does substantially reduce its severity.     

Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis

AIM: To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP). METHODS: SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20 ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n = 21) received no treatment after the SAP model was established; group B (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0,5 h before the SAP model was established; group C (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS: Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the ex- pression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r=-0.748, -0.827, -0.723; P＜0.01). In the second series of experiments, no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase was decreased and the extent of pancreatic necrosis was ameliorated significantly. Compared to SAP control group, the expression of DAF and CD59 in pancreas was reinforced when IL-4 was given before the induction of SAP model (P＜0.01, P＜0.05), but the expression of MCP was not influenced (P＞0.05). The expression of DAF was enhanced, when IL-4 was given after the induction of SAP model (P＜0.05), but the expression of CD59 and MCP did not change (P＞0.05). CONCLUSION: Complement activation regulators may participate in the pathogenesis of pancreatic inflammation. Downregulation of complement activation regulators expression may be one of the causes of pancreatic necrosis. IL-4 treatment may control SAP aggravation by enhancing expression of DAF and CD59 in pancreas and decreasing pancreatic necrosis. Moreover, DAF and CD59 may play an important role in the regulation of complement activation regulators during SAP.     

Role of endogenous and exogenous cholecystokinin in experimental acute pancreatitis induced in rats by the duodenal loop technique

The role of endogenous cholecstokinin (CCK) release and exogenous CCK-8 administration in the development and progression of acute pancreatitis and in the early recovery phase of acute pancreatitis were investigated in rats with closed duodenal loop (CDL)-induced pancreatitis. The subcutaneous injection of CCK-8 (2 μg/kg) stimulated a physiological level of pancreatic enzyme secretion in normal control rats, but did not lead to any biochemical or histological evidence of acute pancreatitis. A higher dose of CCK-8 (8 μg/kg), however, did produce both biochemical and histological evidence of acute pancreatitis in the normal control rats. When 2 μg/kg of CCK-8 was injected subcutaneously in rats 6 and 12h after the creation of the CDL, either the biochemical nor the histological findings of acute pancreatitis showed any progression compared with the changes in controls given to CCK-8. Serum CCK levels, measured by radio-immunoassay, increased significantly from mean levels of 5.39 pg/ml (±0.95 SD) before creation of the CDL to 42.06 pg/ml (±2.27 SD) 6h after, and 41.95 pg/ml (±1.88 SD) 12h after its creation (P<0.01). The difference between serum CCK levels at 6 and 12h was not statistically significant. Following the release of the loop, serum CCK levels decreased gradually, especially in rats in which the loop was released 6h after being created. Although no marked biochemical and histological changes of acute pancreatitis were observed following the admistration of 2 μg/kg of CCK-8 to rats upon release of the loop 6h and 12h after its creation, a higher dose of CCK-8 (8 μg/kg) in these rats adversely affected both the biochemical and histological findings of acute pancreatitis. Based on these findings, it was concluded that neither endogenous CCK release, as a result of the CDL, nor physiological stimulation of the pancreas by exogenous CCK-8 administration, caused progression from edematous to hemorrhagic acute pancreatitis, and neither CCK treatment had any adverse effect on the early recovery phase of CDL-induced acute pancreatitis. A pharmacological dose of CCK, however, exacerbated the acute pancreatitis, even in the early recovery stage.     

α-Lipoic acid protects against cholecystokinin-induced acute pancreatitis in rats

AIM: Alpha-lipoic acid (ALA) has been used as an antioxidant. The aim of this study was to investigate the effect of alpha-lipoic acid on cholecystokinin (CCK)-octapeptide induced acute pancreatitis in rats. METHODS: ALA at 1 mg/kg was intra-peritoneally injected, followed by 75 microg/kg CCK-octapeptide injected thrice subcutaneously after 1, 3, and 5 h. This whole procedure was repeated for 5 d. We checked the pancreatic weight/body weight ratio, the secretion of pro-inflammatory cytokines and the levels of lipase, amylase of serum. Repeated CCK octapeptide treatment resulted in typical laboratory and morphological changes of experimentally induced pancreatitis. RESULTS: ALA significantly decreased the pancreatic weight/body weight ratio and serum amylase and lipase in CCK octapeptide-induced acute pancreatitis. However, the secretion of IL-1beta, IL-6, and TNF-alpha were comparable in CCK octapeptide-induced acute pancreatitis. CONCLUSION: ALA may have a protective effect against CCK octapeptide-induced acute pancreatitis.     

Effects of tetraprenylacetone on pancreatic exocrine secretion and acute pancreatitis in two experimental models in rats

Summary The effects of tetraprenylacetone (TPN), an acyclic polyisoprenoid with antiulcer actions, on pancreatic exocrine secretion, and its preventive and therapeutic effects on acute pancreatitis in two experimental models were studied in rats. Intraduodenal administration of TPN (0, 100, 200 and 400 mg/kg/h) caused dose-dependent increases in pancreatic juice and bicarbonate output without increasing protein output and plasma cholecystokinin (CCK) concentrations. TPN-stimulated pancreatic exocrine secretion was completely abolished by antisecretin serum but it was not by CCK receptor antagonist loxiglumide (50 mg/kg/h). In acute pancreatitis induced by four subcutaneous injections of 20 μg/kg cerulein at hourly intervals over, 3 h, TPN (400 mg/kg) given by an oral route either 1 h before the first cerulein injection or immediately after the last injection significantly reduced the increases in serum amylase and lipase activities and pancreatic wet wt. Pretreatment with TPN caused histologic improvements, whereas posttreatment failed to ameliorate histologic alterations. In severe type of acute pancreatitis induced by retrograde intraductal injection of 1.0 mL/kg of 4% sodium taurocholate, TPN exerted no apparent beneficial effects on biochemical and histologic alterations of acute pancreatitis. It is concluded that TPN given by an oral route stimulates pancreatic exocrine secretion through an increase in endogenous secretin release and causes beneficial effects on the experimental model of mild acute pancreatitis in rats.     

Taraxacum officinale protects against cholecystokinin-induced acute pancreatitis in rats

AIM: Taraxacum officinale (TO) has been frequently used as a remedy for inflammatory diseases. The aim of this study was to investigate the effect of TO on cholecystokinin (CCK)-octapeptide-induced acute pancreatitis in rats.METHODS: TO at 10 mg/kg was orally administered, followed by 75 μg/kg CCK octapeptide injected subcutaneously three times after 1, 3 and 5 h. This whole procedure was repeated for 5 d. We determined the pancreatic weight/body weight ratio, the levels of pancreatic HSP60 and HSP72, and the secretion of pro-inflammatory cytokines. Repeated CCK octapeptide treatment resulted in typical laboratory and morphological changes of experimentally-induced pancreatitis.RESULTS: TO significantly decreased the pancreatic weight/body weight ratio in CCK octapeptide-induced acute pancreatitis. TO also increased the pancreatic levels of HSP60 and HSP72. Additionally, the secretion of IL-6 and TNF-α decreased in the animals treated with TO.CONCLUSION: TO may have a protective effect against CCK octapeptide-induced acute pancreatitis.