Early organ-specific mitochondrial dysfunction of jejunum and lung found in rats with experimental acute pancreatitis

Mittal, Anubhav; Hickey, Anthony J. R.; Chai, Chau C.; Loveday, Benjamin; Thompson, Nichola M.; Dare, Anna J; Delahunt, Brett; Cooper, Garth J. S.; Windsor, John A.; Phillips, Anthony R.J.

doi:10.1111/j.1477-2574.2010.00290.x

Cited by 22 publications

(12 citation statements)

References 52 publications

(68 reference statements)

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“…e mechanisms underlying the development of gut dysmotility are complex. Neural reflexes, hormonal influences, jejunal mitochondrial dysfunction, local molecular inflammatory responses, and the recruitment of activated immune cells into the intestinal muscle are involved [14][15][16][17]. It is well documented that proinflammatory cytokines such as interleukin-1beta (IL-1β) and tumour necrosis factoralpha (TNF-α), released at the early stage of AP, can further worsen gut dysmotility [18,19], thus contributing to severe AP development [20].…”

Section: Introductionmentioning

confidence: 99%

Improving Small Intestinal Motility in Experimental Acute Necrotising Pancreatitis by Modulating the CPI-17/MLCP Pathway Using Chaiqin Chengqi Decoction

Lin

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), a specific inhibitor of myosin light-chain phosphatase (MLCP) regulated by proinflammatory cytokines, is central for calcium sensitisation. We investigated the effects of chaiqin chengqi decoction (CQCQD) on the CPI-17/MLCP pathway in the small intestinal smooth muscle cells (SMCs) and strips (SMS) in an AP model. Necrotising AP was induced in rats by intraperitoneal injections (IPI) of L-ornithine (3.0 g/kg, pH 7.0; hourly × 2) at 1 hour apart; controls received saline. In treatment groups, carbachol (CCh; 60 μg/kg, IPI) or CQCQD (20 g/kg; 2-hourly × 3, intragastric) was administered. The necrotising AP model was associated with systemic inflammation (serum IL-1β and TNF-α) and worsened jejunum histopathology and motility (serum vasoactive intestinal peptide and intestinal fatty acid-binding protein) as the disease progressed. There was decreased intracellular calcium concentration ([Ca2+]i) SMCs. Contractile function of isolated SMCs was reduced and associated with down-regulated expression of key mRNAs and proteins of the CPI-17/MLCP pathway as well as increased IL-1β and TNF-α. CQCQD and CCh significantly reversed these changes and the disease severity. These data suggest that CQCQD can improve intestinal motility by modulating the CPI-17/MLCP pathway in small intestinal smooth muscle during AP.

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Section: Introductionmentioning

confidence: 99%

Improving Small Intestinal Motility in Experimental Acute Necrotising Pancreatitis by Modulating the CPI-17/MLCP Pathway Using Chaiqin Chengqi Decoction

Lin

Zhang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…The main indicator in the clinical course is the severity of the disease. Therefore, early prediction of disease severity by various methods plays a key role in the provision of appropriate and efficient treatment (4). In this regard, various scoring systems have been recommended to determine the disease severity in the early stages.…”

Section: Introductionmentioning

confidence: 99%

Significance of appetite hormone ghrelin and obestatin levels in the assessment of the severity of acute pancreatitis

Kanat¹,

Ayten²,

Aydın³

et al. 2014

Turk J Gastroenterol

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Background/Aims: Due to risk of morbidity and mortality, various tests and scoring systems used in the assessment of the diagnosis and severity of acute pancreatitis disease are gaining more importance every day. Most of the current scoring systems, validated by various parameters, have a sophisticated and complex structure. Research is ongoing to establish a method to diagnose the disease and determine the severity by using different and simple parameters. In this trial, we aimed to investigate the role of the orexigenic "ghrelin" and anorexigenic "obestatin" hormones, if any, on the diagnosis and assessment of the severity of acute pancreatitis. Materials and Methods: A total of 30 patients hospitalized between September 2009 and September 2010 with a diagnosis of acute pancreatitis (AP) and 25 healthy volunteers were enrolled in the trial with a prospective and randomized design. The patients were classified in two groups, mild (Ranson ≤3 and / or Apache II ≤8) and severe (Ranson >3 and/or Apache II >8) cases, as per the Ranson and Apache-II criteria; the ghrelin and obestatin levels in blood samples obtained from the patients were measured using the ELISA method. Results: Twenty-two of the 30 patients (73%) were regarded as mild pancreatitis cases, while 8 cases (27%) were diagnosed as severe pancreatitis. Comparison of the mild and severe pancreatitis groups did not reveal a statistical difference between the two groups in terms of acylated and de-acylated ghrelin values on presentation and following the initiation of oral feeding. Similarly, no significant difference was found in the comparison of the patient and the control groups in terms of acylated and de-acylated ghrelin values on presentation (p=0.863). On the other hand, acylated and de-acylated ghrelin values after initiation of oral feeding were observed to be higher in the patient group (p=0.001, p=0.000). Comparison of these two groups revealed a significant difference in obestatin values, both on presentation and after initiation of oral feeding (p=0.002 and p=0.000). Conclusion: Consistently high serum ghrelin values during pancreatic inflammation suggest that ghrelin may be used as an adjunctive parameter in the monitoring of the course of the disease. On the other hand, high obestatin values in patients on presentation indicate that this hormone is a more significant parameter in terms of diagnosis. However, no correlation was established between these two peptide hormones and the severity of AP.

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“…15,16 The gut-lymph model recognizes the gut dysfunction occurs in the presence of AP. This can be seen as loss of intestinal mucus, 17 endotoxaemia, 18 mitochondrial dysfunction, 19 increased endothelial permeability, 20 and mucosal ischaemia. 21 As a result of ischemic intestinal injury there are significant changes in the composition of lymph draining the intestine, and these changes are toxic to cells and organ systems.…”

Section: Persistent Organ Failurementioning

confidence: 99%

“…25 Gut lymph is toxic. In our laboratory, the toxicity of gut lymph in AP has been assessed at an organelle (mitochondrial function 19 ), cellular (endothelial and cardiac cultures), and whole organ level (isolated perfused heart and lung). 26 Gut lymph, from a rodent model of ischemia-reperfusion injury, infused intravenously into other rats with AP 27 caused lung injury and an increase in AP severity.…”

Section: Persistent Organ Failurementioning

confidence: 99%

Novel strategies for the treatment of acute pancreatitis based on the determinants of severity

Windsor

Escott

Brown

et al. 2017

J of Gastro and Hepatol

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Acute pancreatitis (AP) is a common disease for which a specific treatment remains elusive. The key determinants of the outcome from AP are persistent organ failure and infected pancreatic necrosis. The prevention and treatment of these determinants provides a framework for the development of specific treatment strategies. The gut-lymph concept provides a common mechanism for systemic inflammation and organ dysfunction. Acute and critical illness, including AP, is associated with intestinal ischemia and drastic changes in the composition of gut lymph, which bypasses the liver to drain into the systemic circulation immediately proximal to the major organ systems which fail. The external diversion of gut lymph and the targeting of treatments to counter the toxic elements in gut lymph offers novel approaches to the prevention and treatment of persistent organ failure. Infected pancreatic necrosis is increasingly treated with less invasive techniques, the mainstay of which is drainage, both endoscopic and percutaneous. Further improvements will occur with the strategies to accelerate liquefaction and through a fundamental redesign of drains, both of which will increase drainage efficacy. The determinants of severity and outcome in patients admitted with AP provide the basis for innovative treatment strategies. The priorities are to translate the gut-lymph concept to clinical practice and to improve the design and active use of drains for infected complications of AP.

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Early organ-specific mitochondrial dysfunction of jejunum and lung found in rats with experimental acute pancreatitis

Cited by 22 publications

References 52 publications

Improving Small Intestinal Motility in Experimental Acute Necrotising Pancreatitis by Modulating the CPI-17/MLCP Pathway Using Chaiqin Chengqi Decoction

Improving Small Intestinal Motility in Experimental Acute Necrotising Pancreatitis by Modulating the CPI-17/MLCP Pathway Using Chaiqin Chengqi Decoction

Significance of appetite hormone ghrelin and obestatin levels in the assessment of the severity of acute pancreatitis

Novel strategies for the treatment of acute pancreatitis based on the determinants of severity

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