Arginine induced acute pancreatitis alters the actin cytoskeleton and increases heat shock protein expression in rat pancreatic acinar cells

Tashiro, Mitsuo; Schäfer, Claus; Yao, Hongyu; Ernst, Stephen A.; Williams, John A.

doi:10.1136/gut.49.2.241

Cited by 71 publications

(72 citation statements)

References 43 publications

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“…These findings were in agreement with the results of previous studies which reported these histo-pathological changes after 1 day of induction of AP [19,22,44]. According to Nevalainen and Aho [31], oedema is the most common denominator of AP induced by any method, and reflects inflammatory mechanisms.…”

Section: Discussionsupporting

confidence: 83%

The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats

Sadek

Khattab

2017

Folia Morphol

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Background: Acute pancreatitis (AP) is an inflammatory disease that has an incre- Materials and methods: Thirty-six adult male albino rats were used in this study. Animals were divided into four groups; Control group (Group A; n = 6), Mel group (Group B; n = 6), L-arg group (Group C; n = 12) receiving two doses of L-arg injection with 1 h interval in-between, and L-arg+Mel group (Group D; n = 12) receiving Mel 1 h after each L-arg injection. 24 h after the second L-arg injection, the serum levels of amylase (AM), lipase (LP), interleukin-6 (IL-6) and (Folia Morphol 2017; 76, 1: 66-73)

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Section: Discussionsupporting

confidence: 83%

The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats

Sadek

Khattab

2017

Folia Morphol

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“…In addition, a more pronounced induction of selective HSPs can protect against acute pancreatitis, depending on the model of acute pancreatitis used (32)(33)(34). In this context, HSP27 and HSP70 have been extensively studied.…”

Section: Discussionmentioning

confidence: 99%

Regulation of HSP60 and the role of MK2 in a new model of severe experimental pancreatitis

Ochs

Gao

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Göke B, Schäfer C. Regulation of HSP60 and the role of MK2 in a new model of severe experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol 297: G981-G989, 2009. First published August 20, 2009; doi:10.1152/ajpgi.00225.2009.-The objective of this study was to investigate the role of MAPKAP kinase 2 (MK2) and heat shock protein (HSP) HSP60 in the pathogenesis of a new model of severe acute pancreatitis (AP). MK2 plays a significant role in the regulation of cytokines. It has been shown that induction and expression of several HSPs can protect against experimental pancreatitis. Interplay between both systems seems of high interest. Mice with a homozygous deletion of the MK2 gene were used. Severe AP was induced by combined intraperitoneal injections of cerulein with lipopolysaccharide (LPS). Severity of AP was assessed by biochemical markers and histology. The serum IL-6 and lung myeloperoxidase (MPO) levels were determined for assessing the extent of systemic inflammatory response. Expression of HSP25, HSP60, HSP70, and HSP90 was analyzed by Western blotting. Repeated injections of cerulein alone or cerulein plus LPS (CerϩLPS) resulted in local inflammatory responses in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the CerϩLPS group. Compared with the C57Bl wild-type mice, the MK2Ϫ/Ϫ mice presented with significant milder pancreatitis and attenuated responses of serum amylase and trypsinogen activity. Furthermore, serum IL-6 was decreased as well as lung MPO activity. Injection of LPS alone displayed neither pancreatic inflammatory responses nor alterations of pancreatic enzyme activities but evidently elevated serum IL-6 levels and increased lung MPO activity. In contrast hereto, in the MK2Ϫ/Ϫ mice, these changes were much milder. Increased expression of HSP25 and HSP60 occurred after induction of AP. Especially, HSP60 was robustly elevated after CerϩLPS treatment, in both MK2Ϫ/Ϫ and wild-type mice. Thus the homozygous deletion of the MK2 gene ameliorates the severity of acute pancreatitis and accompanying systemic inflammatory reactions in a new model of severe acute pancreatitis. Our data support the hypothesis that MK2 participates in the multifactorial regulation of early inflammatory responses in AP, independently of the regulation of stress proteins like HSP25 and HSP60 and most likely due to its effect on cytokine regulation.

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“…However, in the rat model of L-arginine- induced pancreatitis, cytoskeletal changes (27), the involvement of oxygen free radicals, NO, and inflammatory mediators (9) have all been suggested to play roles in the induction of pancreatitis. These potential mediators of L-arginine-induced pancreatitis have only been studied at later time points, thereby making it difficult to link these mediators with the initial events.…”

Section: Discussionmentioning

confidence: 99%

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

Dawra

Sharif

Phillips

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

163

131

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Dawra R, Sharif R, Phillips P, Dudeja V, Dhaulakhandi D, Saluja AK. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol 292: G1009 -G1018, 2007. First published December 14, 2006; doi:10.1152/ajpgi.00167.2006.-The pathogenesis of acute pancreatitis is not fully understood. Experimental animal models that mimic human disease are essential to better understand the pathophysiology of the disease and to evaluate potential therapeutic agents. Given that the mouse genome is known completely and that a large number of strains with various genetic deletions are available, it is advantageous to have multiple reliable mouse models of acute pancreatitis. Presently, there is only one predominant model of acute pancreatitis in mice, in which hyperstimulatory doses of cholecystokinin or its analog caerulein are administered. Therefore, the aim of this study was to develop another mouse model of acute pancreatitis. In this study, C57BL/6 mice were injected intraperitoneally with L-arginine in two doses of 4 g/kg each, 1 h apart. Serum amylase, myeloperoxidase, and histopathology were examined at varying time points after injection to assess injury to the pancreas and lung. We found that injection of L-arginine was followed by significant increases in plasma amylase and pancreatic myeloperoxidase accompanied by marked histopathological changes. The injury to the pancreas was slow to develop and peaked at 72 h. Subsequent to peak injury, the damaged areas contained collagen fibers as assessed by increased Sirius red staining. In contrast, D-arginine or other amino acids did not cause injury to the pancreas. In addition, acute inflammation in the pancreas was associated with lung injury. Our results indicate that administration of L-arginine to mice results in severe acute pancreatitis. This model should help in elucidating the pathophysiology of pancreatitis.pancreas; lung injury; fibrosis ACUTE PANCREATITIS IS AN INFLAMMATORY disease of the pancreas resulting in significant morbidity and mortality (13). Various causes, including gallstones, alcohol, trauma, infections, and genetic alterations, have been implicated in the causation of this disease (1, 23). Although our understanding of the cell biology of the exocrine pancreas and epidemiology of pancreatitis has increased greatly in recent years, our knowledge of its pathophysiology and the ability to prevent or treat pancreatitis remain limited (23). This can partially be attributed to the paucity of clinical material from the early stages of the disease available for research. To overcome this and to study the effect of new therapeutic agents, different experimental animal models of pancreatitis have been developed. Our present limited understanding about the events associated with the development of the disease is based on the use of these experimental models (21). Among the animals used for developing experimental models, the mouse is ideal because of the availability of several genetic man...

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Arginine induced acute pancreatitis alters the actin cytoskeleton and increases heat shock protein expression in rat pancreatic acinar cells

Cited by 71 publications

References 43 publications

The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats

The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats

Regulation of HSP60 and the role of MK2 in a new model of severe experimental pancreatitis

Development of a new mouse model of acute pancreatitis induced by administration of l-arginine

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