Pharmacological Prevention and Treatment of Acute Pancreatitis: Where Are We Now?

Lankisch, P. G.; Lerch, Markus M.

doi:10.1159/000090318

Cited by 33 publications

(24 citation statements)

References 194 publications

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“…Although the other three scores did not show any significant difference, a decrease in inflammation and perivascular infiltrate score by 35% in experimental rat models with cerulein-induced acute pancreatitis administered with one dose of everolimus by oral gavage and a decrease by 75% in those administered with two doses of everolimus were the most significant and promising findings of this study (Table 4). Because the mortality rate significantly increases with multiple organ failure because of SIRS, the specific inhibition of inflammatory signalling pathways presents a great potential as pharmacological treatment (2,6,21). The significant decrease in inflammation and perivascular infiltrate score may imply that everolimus treatment directly or indirectly interferes with the inflammatory signalling pathway, thereby inhibiting SIRS.…”

Section: Discussionmentioning

confidence: 99%

Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis

Özkardeş¹,

Bozkurt²,

Dumlu³

et al. 2015

UCD

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Objective: To analyze the biochemical and histopathological effects of everolimus in an experimental rat model of cerulein-induced acute pancreatitis. The aim of the present study was to determine the effects of everolimus on blood biochemical parameters and tissue histopathology in an experimental rat model of cerulein-induced acute pancreatitis. Material and Methods:In 30 Wistar albino rats (male; 240-260 g), acute pancreatitis was induced by an intraperitoneal injection of cerulein (50 μg/kg) administered twice in 2 h. They were equally divided into the following three groups: 0.9% isotonic solution (Group 1; control), everolimus once (Group 2), and everolimus twice (Group 3) by oral gavage after cerulein injection. Thirty hours after the induction of pancreatitis, blood samples were collected by direct intracardiac puncture, rats were sacrificed, and pancreatic tissue samples were obtained.Results: Biochemical analyses of the blood samples showed statistically significant difference in red blood cell count as well as hemoglobin, hematocrit, urea, and alanine transaminase levels among the study groups (p<0.05 in all). Everolimus proved to significantly increase red blood cell count in a dose-independent manner. Hemoglobin and hematocrit levels significantly increased only after treatment with one dose of everolimus. Urea level was significantly different between the Groups 2 and 3; however, no change was observed in both groups when compared with the control. Alanine transaminase level significantly decreased only after treatment with two doses of everolimus. Histopathological analyses revealed that everolimus significantly decreased inflammation and perivascular infiltrate in a dose-dependent manner (35% in Group 2, 75% in Group 3; p=0.048). Conclusion:Treatment with two doses of everolimus improved some biochemical and histopathological parameters of experimental rat models of cerulein-induced acute pancreatitis and implied the specific inhibition of inflammatory response pathways. Keywords: Pancreatitis, cerulein, everolimus, inflammation INTRODUCTIONAcute pancreatitis is a localized inflammatory condition with a high mortality rate (2.1%-9.2%) worldwide. Because of its potential to trigger systemic inflammatory response, it can cause multiple organ failure (1, 2). The common causes of acute pancreatitis are alcohol abuse or gallstone disease (60%-75% of the cases) followed by hypertriglyceridemia, hyperparathyroidism, pancreatic malignancy, endoscopic retrograde cholangiopancreatography, trauma, infectious agents (increasingly associated with HIV infection), drugs (such as tetracycline, azathioprine, ethinyl estradiol, mercaptopurine, and sulfamethoxazole), autoimmunity, abdominal trauma, ischemia, diabetes mellitus, porphyria, and heredity (3-5).Although the disease is common, the treatment of acute pancreatitis is still very limited. There are only a number of pharmacological approaches, which are mostly supportive involving adequate fluid resuscitation and oxygen supplementation, to maintain normal art...

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Section: Discussionmentioning

confidence: 99%

Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis

Özkardeş¹,

Bozkurt²,

Dumlu³

et al. 2015

UCD

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“…In SAP, MODS, a consequence of the systemic inflammatory response syndrome, is a contributor to high mortality in the early phase [1] . It is conceivable that the release of mediators from the excess of activated macrophages/monocytes and neutrophils may lead to remote organ injury [1] .…”

Section: Discussionmentioning

confidence: 99%

“…It is conceivable that the release of mediators from the excess of activated macrophages/monocytes and neutrophils may lead to remote organ injury [1] . Serum HMGB1 levels are significantly elevated in patients with SAP on admission [12] .…”

Section: Discussionmentioning

confidence: 99%

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Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats

Yang¹,

Yan²,

Yin³

et al. 2008

WJG

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AIM:To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP). METHODS: A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS: Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 ± 0.42 vs 9.76 ± 0.45, P < 0.01), pulmonary histological scores (7.1 ± 0.7 vs 8.4 ± 1.1, P < 0.01), serum AST (667 ± 103 vs 1 368 ± 271, P < 0.01), ALT (446 ± 91 vs 653 ± 98, P < 0.01) and Cr (1.2 ± 0.3 vs 1.8 ± 0.3, P < 0.01) levels. SAP rats had a median survival time

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“…Histopathological scores were higher in the P and T groups than in the C group, and lower in the T group than in the P group at 2 and 6 h. * P<0.05 as compared with the C group, # P<0.05 as compared with the P group. Data are expressed as mean±SD (n=8) 4 Discussion SAP is associated complications including SIRS, MODS, ALI, and local complications within the pancreata (Ammori, 2003;Lankisch and Lerch, 2006). Among the extrapancreatic complications of SAP, ALI is most frequently associated with death.…”

Section: Fig 2 Pathological Changes In the Pancreatamentioning

confidence: 99%

Clodronate-containing liposomes attenuate lung injury in rats with severe acute pancreatitis

Dang

Jiang

Chen

et al. 2010

J. Zhejiang Univ. Sci. B

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Abstract:Objectives: Severe acute pancreatitis (SAP) can lead to acute lung injury (ALI). The purpose of this paper is to investigate the protective effect of clodronate-containing liposomes on ALI in rats with SAP. Methods: The thin film method was used to prepare liposomes. Sprague-Dawley rats were randomly divided into three groups. After the SAP model was established by injecting 5% (w/v) sodium taurocholate (2 ml/kg body weight) into the subcapsular space of the pancreata, normal saline was administered to the control (C) group, phosphate buffer solution (PBS)-containing liposome to the P group, and clodronate-containing liposome to the T group through tail veins. Blood samples were obtained from the superior mesenteric vein at 2 and 6 h to measure the levels of amylase, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Morphological changes in the pancreata and lung were observed using hematoxylin and eosin (H&E) staining, while cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). In addition, the macrophage marker cluster of differentiation 68 (CD68) in lung tissue was detected with immunohistochemistry. Results: Blood levels of amylase, IL-6, and TNF-α were significantly increased in the P group compared to those in the T group (P<0.05). In the T group, large numbers of TUNEL-positive cells were observed, but no or few in the C and P groups. Gross inspection and H&E staining of pancreata and lung showed dramatic tissue damage, including inflammation and necrosis in the P group. Less remarkable changes were noted in the T group, and the C group exhibited normal histology. The histological scores according to Kaiser's criteria were consistent with H&E findings. The number of CD68-positive macrophages decreased in the T group. Conclusions: Clodronate-containing liposomes have a protective effect against ALI in rats with SAP. Blockade of macrophages may represent a novel therapeutic strategy in SAP.

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Pharmacological Prevention and Treatment of Acute Pancreatitis: Where Are We Now?

Cited by 33 publications

References 194 publications

Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis

Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis

Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats

Clodronate-containing liposomes attenuate lung injury in rats with severe acute pancreatitis

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