Protective Effects of Baicalin and Octreotide on Multiple Organ Injury in Severe Acute Pancreatitis

Ubiquitin-specific protease 25 (USP25) plays an important role in inflammation and immunity. However, the role of USP25 in acute pancreatitis (AP) is still unclear. To evaluate the role of USP25 in AP, we conducted research on clinical AP patients, USP25wild-type(WT)/USP25 knockout (USP25−/−) mice, and pancreatic acinar cells. Our results showed that serum USP25 concentration was higher in AP patients than in healthy controls and was positively correlated with disease severity. AP patients’ serum USP25 levels after treatment were significantly lower than that at the onset of AP. Moreover, USP25 expression was upregulated in cerulein-induced AP in mice, while USP25 deficiency attenuates AP and AP-related multiple organ injury. In vivo and in vitro studies showed that USP25 exacerbates AP by promoting the release of pro-inflammatory factors and destroying tight junctions of the pancreas. We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 (STAT3) pathway. Targeting the action of USP25 may present a potential therapeutic option for treating AP.

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Targeting neutrophil extracellular traps in severe acute pancreatitis treatment

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284820974913 ◽

2020 ◽

Vol 13 ◽

pp. 175628482097491

Author(s):

Jing Hu ◽

Hongxin Kang ◽

Huan Chen ◽

Jiaqi Yao ◽

Xiaolin Yi ◽

...

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Inflammatory Cells ◽

Neutrophil Extracellular Traps ◽

Multiple Organ ◽

Organ Injury ◽

Normal Tissues ◽

Pathogen Invasion ◽

Extracellular Traps ◽

Abdominal Disease

Severe acute pancreatitis (SAP) is a critical abdominal disease associated with high death rates. A systemic inflammatory response promotes disease progression, resulting in multiple organ dysfunction. The functions of neutrophils in the pathology of SAP have been presumed traditionally to be activation of chemokine and cytokine cascades accompanying the inflammatory process. Recently, since their discovery, a new type of antimicrobial mechanism, neutrophil extracellular traps (NETs), and their role in SAP, has attracted widespread attention from the scientific community. Significantly different from phagocytosis and degranulation, NETs kill extracellular microorganisms by releasing DNA fibers decorated with granular proteins. In addition to their strong antimicrobial functions, NETs participate in the pathophysiological process of many noninfectious diseases. In SAP, NETs injure normal tissues under inflammatory stress, which is associated with the activation of inflammatory cells, to cause an inflammatory cascade, and SAP products also trigger NET formation. Thus, due to the interaction between NET generation and SAP, a treatment targeting NETs might become a key point in SAP therapy. In this review, we summarize the mechanism of NETs in protecting the host from pathogen invasion, the stimulus that triggers NET formation, organ injury associated with SAP involving NETs, methods to interrupt the harmful effects of NETs, and different therapeutic strategies to preserve the organ function of patients with SAP by targeting NETs.

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Protective Effects of Emodin-Induced Neutrophil Apoptosis via the Ca2+-Caspase 12 Pathway against SIRS in Rats with Severe Acute Pancreatitis

BioMed Research International ◽

10.1155/2016/1736024 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Gui-Jun Wang ◽

Yue Wang ◽

Yong-Sheng Teng ◽

Fa-Lv Sun ◽

Hong Xiang ◽

...

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Multiple Organ ◽

Neutrophil Apoptosis ◽

Protective Effects ◽

Expression Levels ◽

Beneficial Effects ◽

Caspase 12 ◽

Underlying Mechanisms ◽

Active Fragments

Severe acute pancreatitis (SAP) results in high mortality. This is partly because of early multiple organ dysfunction syndromes that are usually caused by systemic inflammatory response syndrome (SIRS). Many studies have reported the beneficial effects of emodin against SAP with SIRS. However, the exact mechanism underlying the effect of emodin remains unclear. This study was designed to explore the protective effects and underlying mechanisms of emodin against SIRS in rats with SAP. In the present study, cytosolic Ca2+ levels, calpain 1 activity, and the expression levels of the active fragments of caspases 12 and 3 decreased in neutrophils from rats with SAP and increased after treatment with emodin. Delayed neutrophil apoptosis occurred in rats with SAP and emodin was able to reverse this delayed apoptosis and inhibit SIRS. The effect of emodin on calpain 1 activity, the expression levels of the active fragments of caspases 12 and 3, neutrophil apoptosis, and SIRS scores were attenuated by PD150606 (an inhibitor of calpain). These results suggest that emodin inhibits SIRS in rats with SAP by inducing circulating neutrophil apoptosis via the Ca2+-calpain 1-caspase 12-caspase 3 signaling pathway.

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Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury

World Journal of Gastroenterology ◽

10.3748/wjg.v23.i46.8169 ◽

2017 ◽

Vol 23 (46) ◽

pp. 8169-8181 ◽

Cited By ~ 6

Author(s):

Lv Zhu ◽

Jun-Yi Li ◽

Yu-Mei Zhang ◽

Hong-Xin Kang ◽

Huan Chen ◽

...

Keyword(s):

Acute Pancreatitis ◽

Multiple Organ ◽

Organ Injury ◽

Pharmacokinetics And Pharmacodynamics ◽

Multiple Organ Injury

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Research on Scutellarin Parenteral Solution’s Protective Effects in Rats with Severe Acute Pancreatitis and Multiple Organ Injuries

Inflammation ◽

10.1007/s10753-011-9404-7 ◽

2011 ◽

Vol 35 (3) ◽

pp. 1005-1014 ◽

Cited By ~ 4

Author(s):

Chen Hanqing ◽

Zhang Xiping ◽

Ou Jingmin ◽

Jiang Jun ◽

Wu Dijiong

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Multiple Organ ◽

Protective Effects

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Recombinant HDL (Milano) protects endotoxin-challenged rats from multiple organ injury and dysfunction

Biological Chemistry ◽

10.1515/hsz-2014-0188 ◽

2015 ◽

Vol 396 (1) ◽

pp. 53-60 ◽

Cited By ~ 14

Author(s):

Xinbo Zhang ◽

Luya Wang ◽

Baosheng Chen

Keyword(s):

Adhesion Molecule ◽

Multiple Organ ◽

Organ Injury ◽

Intercellular Adhesion Molecule ◽

Protective Effects ◽

Intercellular Adhesion Molecule 1 ◽

Anti Oxidant ◽

Anti Inflammatory ◽

Multiple Organ Injury

Abstract Endotoxemia, the systemic inflammatory host response to infection, leads to severe septic shock and multiple organ injury and dysfunction syndrome (MOPS), which cause mortality. Apolipoprotein A-IMilano (apoAIM), a naturally occurring cysteine mutant of apoAI with dimers as its effective form, showed an enhanced cardiovascular protective activity compared with wild-type apoAI (apoAIwt). To investigate the role of recombinant high-density lipoprotein (rHDL) reconstituted with apoAIM (rHDLM) on endotoxemia and MOPS, we examined the anti-inflammatory, anti-oxidant, and protective effects of this cysteine mutant against organ injury in endotoxin-challenged rat models compared with rHDLwt. In the present study, we demonstrated for the first time that pretreatment with rHDLM significantly attenuated liver and renal dysfunction and histopathological features of lung injury in endotoxin-challenged endotoxemia rats. Administration of rHDLM to endotoxemia rats dramatically suppressed proinflammatory cytokines and adhesion molecule increase in tumor necrosis factor α, interleukin 1β, interleukin 6, and intercellular adhesion molecule 1. In addition, rHDLM pretreatment inhibited lipid peroxidation and enhanced total antioxidant capacity in vivo. In comparison with rHDLwt, rHDLM showed enhanced capacity on anti-inflammatory and anti-oxidant functions. In summary, administration of rHDLM protected endotoxin-challenged endotoxemia and MOPS through enhanced anti-inflammatory and anti-oxidant properties.

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