Tetramethylpyrazine (TMP) protects rats against acute pancreatitis through NF-κB pathway

Chen, Longying; Chen, Yongjun; Huang, Yun; Zhang, Jianli

doi:10.1080/21655979.2019.1613103

Cited by 15 publications

(10 citation statements)

References 45 publications

(43 reference statements)

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“…Interestingly, macrophage infiltration was significantly reduced after heparin treatment, and the expression of inflammatory factors TNF-α, IL-6, and IL-1β was significantly decreased. This result is similar to the findings of Chen et al [ 34 ]. They found that Tetramethylpyrazine reduced the severity of AP by decreasing the levels of pro-inflammatory factors TNF-α and IL-6.…”

Section: Discussionsupporting

confidence: 93%

Heparin-binding protein (HBP) worsens the severity of pancreatic necrosis via up-regulated M1 macrophages activation in acute pancreatitis mouse models

Zhou

Chen

et al. 2021

Bioengineered

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Acute pancreatitis (AP) is one of the most widespread clinical emergencies. Macrophages are the most common immune cells in AP pancreatic tissue and are closely associated with pancreatic necrosis and recovery. The level of heparin-binding protein (HBP) is closely linked to inflammation. In this study, we assessed the effect of HBP on AP tissue necrosis severity and whether HBP is associated with M1 macrophages in pancreatic necrosis. We observed the dynamic changes of HBP levels in the pancreas during acute inflammation in the caerulein-induced AP mice model. We used hematoxylin–eosin staining to evaluate pancreatic edema and necrosis, and to detect infiltration of macrophages by immunohistochemistry. Moreover, expressions of the maker and cytokines of macrophages, including inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNA, were detected by real-time polymerase-chain reaction (RT-PCR). High levels of HBP in the pancreas were detected at 48 h, and heparin inhibited HBP expression in AP pancreatic tissue. Inhibiting HBP expression by injecting heparin before AP can alleviate pancreatic necrosis and inhibit F4/80 labeled M1 macrophage infiltration and IL-6, TNF-α, and iNOS mRNA expression. Clodronate liposome (CLDL) intraperitoneally treated mice showed no change in pancreatic HBP levels, but pancreatic macrophage-specific antigen F4/80 and TNF-α, IL-1β, and IL-6 mRNA levels decreased after CLDL treatment. HBP is critical for pancreatic necrosis response in acute pancreatitis by increasing the infiltration of M1 macrophages and promoting the secretion of inflammatory factors, such as TNF-α, IL-6, IL-1β, which can be reduced by heparin.

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Section: Discussionsupporting

confidence: 93%

Heparin-binding protein (HBP) worsens the severity of pancreatic necrosis via up-regulated M1 macrophages activation in acute pancreatitis mouse models

Zhou

Chen

et al. 2021

Bioengineered

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“…Previous studies have also reported the ability of rupatadine to inhibit NF-κB activity and TNF-α expression (Mullol et al 2008;Queralt et al 2000). We assume that the inhibition of the NF-κB/TNF-α pathway mediates the therapeutic effect of rupatadine against AP consistent with (Chen et al 2019). The increased IL-1β production in the AP group was consistent with the finding of (Wu et al 2021) who reported that IL-1β production by activated neutrophils causes more tissue damage during AP progression.…”

Section: R a F Tsupporting

confidence: 70%

Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation

Mohamed

Mohammed

Khalaf

2022

Can. J. Physiol. Pharmacol.

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Acute pancreatitis (AP) is an abrupt inflammatory disorder causing high morbidity and mortality. As AP is an insidious medical emergency, a curative modality is required instead of a preventive measure. Thus, we investigated the possible curative effect of rupatadine on a rat model of AP. Rupatadine is a potent histamine receptor 1 (H1R) and platelet-activating factor (PAF) blocker. We used four groups of six Wistar rats as follows: the control group received vehicle; the rupatadine control group received rupatadine as 6 mg/kg orally; the AP group received l-arginine intraperitoneally, and the treatment group received rupatadine at 1, 6, and 24 h after l-arginine injection. The levels of serum amylase, pancreatic oxidative parameters, and pancreatic cytokines were measured. PAF, histamine, and myeloperoxidase levels were determined in the pancreas. Histopathological and immunohistochemical examinations were performed to determine nuclear factor kappa-B (NF-κB) and caspase 3 expressions. Oxidative damage and severe inflammation were detected in the pancreas of the AP group. Rupatadine reduced the oxidative damage and the levels of proinflammatory cytokines, PAF, histamine, myeloperoxidase, NF-κB, and caspase 3 expressions. It restored the pancreatic acini to almost normal condition. Rupatadine induced important anti-inflammatory and antiapoptotic effects against l-arginine-induced AP.

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“…Accumulating evidence demonstrates that cell apoptosis represents a favorable response during the course of SAP [11][12][13][14]. Apoptosis and necrosis, two forms of cell death, are key pathological responses of SAP.…”

Section: Introductionmentioning

confidence: 99%

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

et al. 2020

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Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodiumtaurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Histopathological staining, serum amylase, endotoxin and inflammatory mediators were measured. Cell apoptosis, apoptosis-related proteins and signaling pathway were also evaluated. Our results demonstrated that APD treatment significantly attenuated pancreatic damage and decreased the serum levels of amylase, endotoxin, TNF-α, IL-1 and IL-6 in rats with SAP. Notably, APD treatment enhanced cell apoptosis and reduced necrosis in pancreatic tissues, as evidenced by Tunnel staining, the increased pro-apoptosis proteins (Cleaved-caspase-3 and bax) and decreased anti-apoptosis protein (Bcl-2). Moreover, the effect of APD on cell apoptosis was further confirmed by the regulatory pathway of PI3K/AKT and NF-kB signaling pathway. These results suggest that APD attenuates the severity of SAP by enhancing cell apoptosis via suppressing PI3K/AKT signaling pathway. Our findings provide new insights for understanding the effectiveness of APD in patients with SAP. Keywords APD • Severe acute pancreatitis • Apoptosis • PI3K/AKT signaling pathway Abbreviations AKT(PKB) Protein kinase B ANOVA One-way analysis of variance APD Abdominal paracentesis drainage Bcl-2 B-cell lymphoma 2 Caspase3 Cysteine aspartic acid protease 3 ELISA Enzyme-linked immunosorbent assay IL Interleukin MAP Mild acute pancreatitis MODS Multiple organ dysfunction syndrome NF-kB Nuclear factor kappa-light-chain-enhancer of activated B cells PAAF Pancreatitis associated ascitic fluids PI3K Phosphatidylinositide 3-kinases SAP Severe acute pancreatitis SIRS Systemic inflammatory response syndrome TNF-α TNF-α

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Tetramethylpyrazine (TMP) protects rats against acute pancreatitis through NF-κB pathway

Cited by 15 publications

References 45 publications

Heparin-binding protein (HBP) worsens the severity of pancreatic necrosis via up-regulated M1 macrophages activation in acute pancreatitis mouse models

Heparin-binding protein (HBP) worsens the severity of pancreatic necrosis via up-regulated M1 macrophages activation in acute pancreatitis mouse models

Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

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