scholarly journals High-Fat Diet Aggravates the Intestinal Barrier Injury via TLR4-RIP3 Pathway in a Rat Model of Severe Acute Pancreatitis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Ying-ru Su ◽  
Yu-pu Hong ◽  
Fang-chao Mei ◽  
Chen-yang Wang ◽  
Man Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Severe Acute Pancreatitis ◽  
High Fat Diet ◽  
Sodium Taurocholate ◽  
Intestinal Barrier ◽  
High Body Mass Index ◽  
High Fat ◽  
Junction Protein

Objective. For patients with severe acute pancreatitis (SAP), a high body mass index (BMI) increases the possibility of infection derived from the intestine. In this study, we evaluate whether TAK242 can alleviate severe acute pancreatitis-associated injury of intestinal barrier in high-fat diet-fed rats. Methods. A SAP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty Sprague-Dawley (SD) adult rats were randomly divided into five groups: standard rat chow (SRC) normal (SN), SRC SAP (SAP), high-fat diet normal (HN), HFD SAP (HSAP), and TLR4 inhibitor pretreatment HFD SAP (HAPT) groups. Intraperitoneal injection of 3 mg/kg TAK242 was administered 30 minutes before SAP model establishment in the HAPT group. Rats were sacrificed 12 hours after SAP modeling, followed by blood and pancreatic and distal ileum tissue collection for further analyses. Changes in the pathology responses of the rats in each group were assessed. Result. Analyses of serum amylase, lipase, cholesterol, triglyceride, IL-1β, IL-6, DAO, and serum endotoxin as well as tight junction protein expression including zonula occluden-1 and occludin indicated that high-fat diet aggravated SAP-induced intestinal barrier injury via increasing inflammatory response. In addition, the level of necroptosis was significantly higher in the SAP group compared with the SN group while the HSAP group exhibited more necroptosis compared with the SAP group, indicating the important role of necroptosis in pancreatitis-associated gut injury and illustrating that high-fat diet aggravated necroptosis of the ileum. Pretreatment with TLR4 inhibitor significantly alleviated inflammatory response and reduced necroptosis and level of oxidative stress while improving intestinal barrier function. Conclusion. High-fat diet aggravated SAP-induced intestinal barrier injury via inflammatory reactions, necroptosis, and oxidative stress. Inhibition of TLR4 by TAK242 reduced inflammation, alleviated necroptosis, and lowered the level of oxidative stress and then protected the intestinal barrier dysfunction from SAP in high-fat diet-fed rats.

scholarly journals High-Fat Diet Aggravates Acute Pancreatitis via TLR4-Mediated Necroptosis and Inflammation in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-pu Hong ◽  
Jia Yu ◽  
Ying-ru Su ◽  
Fang-chao Mei ◽  
Man Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
High Fat Diet ◽  
Sodium Taurocholate ◽  
The Body ◽  
Chow Diet ◽  
High Fat ◽  
Serum Free Fatty Acid ◽  
Tlr4 Signaling ◽  
Inflammatory Status

High-fat diet (HFD) often increases oxidative stress and enhances inflammatory status in the body. Toll-like receptor 4 (TLR4) is widely expressed in the pancreatic tissues and plays an important role in pancreatitis. This study is aimed at investigating the effect of HFD on acute pancreatitis (AP) and the role of TLR4-mediated necroptosis and inflammation in this disease. Weight-matched rats were allocated for an 8-week feeding on the standard chow diet (SCD) or HFD, and then, the AP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats were sacrificed at an indicated time point after modeling. Additionally, inhibition of TLR4 signaling by TAK-242 in HFD rats with AP was conducted in vivo. The results showed that the levels of serum free fatty acid (FFA) in HFD rats were higher than those in SCD rats. Moreover, HFD rats were more vulnerable to AP injury than SCD rats, as indicated by more serious pathological damage and much higher pancreatic malondialdehyde (MDA) and lipid peroxidation (LPO) levels as well as lower pancreatic superoxide dismutase (SOD) activities and reduced glutathione (GSH) contents and more intense infiltration of MPO-positive neutrophils and CD68-positive macrophages. In addition, HFD markedly increased the expressions of TLR4 and necroptosis marker (RIP3) and aggravated the activation of NF-κB p65 and the expression of TNF-α in the pancreas of AP rats at indicated time points. However, TLR4 inhibition significantly attenuated the structural and functional damage of the pancreas induced by AP in HFD rats, as indicated by improvement of the above indexes. Taken together, these findings suggest that HFD exacerbated the extent and severity of AP via oxidative stress, inflammatory response, and necroptosis. Inhibition of TLR4 signaling by TAK-242 alleviated oxidative stress and decreased inflammatory reaction and necroptosis, exerting a protective effect during AP in HFD rats.

scholarly journals Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xian-lin Wu ◽  
Jie-xing Li ◽  
Zhen-dong Li ◽  
Da-sheng Liu ◽  
Su-hong Lu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Free Radical ◽  
Bile Duct ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Protective Effect ◽  
Severe Acute Pancreatitis ◽  
Sodium Taurocholate ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction

Tet is a type of alkaloid extracted fromStephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

Amla (Emblica officinalis) improves hepatic and renal oxidative stress and the inflammatory response in hypothyroid female wistar rats fed with a high-fat diet

2018 ◽  
Vol 29 (2) ◽  
pp. 175-184 ◽  
Author(s):  
P. Rajaa Muthu ◽  
Zachariah Bobby ◽  
P. Sankar ◽  
V. Vickneshwaran ◽  
Sajini Elizabeth Jacob
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Molecular Techniques ◽  
Emblica Officinalis ◽  
High Fat ◽  
Tnf Α ◽  
Female Wistar Rats ◽  
Liver And Kidney

AbstractBackground:We investigated the protective effects of amla (Emblica officinalis) on the pathogenesis of oxidative stress (OS) and inflammatory response in hypothyroid rats fed with a high-fat diet (HFD) as an experimental model of hypothyroidism (HT) with obesity.Methods:A total of 80 female wistar rats (5-months-old) were divided into eight different groups. Propylthiouracil (PTU) and HFD were used to induce the experimental HT and obesity, respectively. The euthyroid and hypothyroid rats were fed either normal chow or HFD with and without amla extract (AE, 100 mg/kg bw/day) for 6 weeks. The blood and tissues, liver and kidney OS and inflammatory parameters were studied using appropriate biochemical and molecular techniques.Results:PTU and HFD per se caused OS and inflammatory response as evidenced by increased plasma MDA, TNF-α, CRP and GPx in association with decreased levels of TAS and reduced glutathione (GSH). The proteomic analysis revealed that the expressions of pERK, pP38, TNF-α, IL6, COX2 and NOX-4 were up-regulated in the liver and kidney of these rats. In addition, all these metabolic derangements were further augmented when HT was followed by the addition of HFD. This suggested that there was a synergism between HT and the intake of HFD on the development of OS and inflammatory response.Conclusions:The treatment with amla fruit extract significantly restored the redox imbalance and inflammatory signaling and ameliorated OS and inflammatory response, suggesting the use of this natural compound as an alternative remedy or adjuvant for the management of metabolic complications concomitant with HT.

scholarly journals Attenuation of Oxidative Stress and Inflammatory Response by Chronic Cannabidiol Administration Is Associated with Improved n-6/n-3 PUFA Ratio in the White and Red Skeletal Muscle in a Rat Model of High-Fat Diet-Induced Obesity

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1603
Author(s):  
Patrycja Bielawiec ◽  
Ewa Harasim-Symbor ◽  
Klaudia Sztolsztener ◽  
Karolina Konstantynowicz-Nowicka ◽  
Adrian Chabowski
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Inflammatory Response ◽  
High Fat Diet ◽  
Gastrocnemius Muscle ◽  
High Fat ◽  
Pufa Ratio ◽  
Oxidative Stress Parameters ◽  
Treatment Of Obesity ◽  
And Oxidative Stress

The consumption of fatty acids has increased drastically, exceeding the nutritional requirements of an individual and leading to numerous metabolic disorders. Recent data indicate a growing interest in using cannabidiol (CBD) as an agent with beneficial effects in the treatment of obesity. Therefore, our aim was to investigate the influence of chronic CBD administration on the n-6/n-3 polyunsaturated fatty acids (PUFAs) ratio in different lipid fractions, inflammatory pathway and oxidative stress parameters in the white and red gastrocnemius muscle. All the designed experiments were performed on Wistar rats fed a high-fat diet (HFD) or a standard rodent diet for seven weeks and subsequently injected with CBD (10 mg/kg once daily for two weeks) or its vehicle. Lipid content and oxidative stress parameters were assessed using gas–liquid chromatography (GLC), colorimetric and/or immunoenzymatic methods, respectively. The total expression of proteins of an inflammatory pathway was measured by Western blotting. Our results revealed that fatty acids (FAs) oversupply is associated with an increasing oxidative stress and inflammatory response, which results in an excessive accumulation of FAs, especially of n-6 PUFAs, in skeletal muscles. We showed that CBD significantly improved the n-6/n-3 PUFA ratio and shifted the equilibrium towards anti-inflammatory n-3 PUFAs, particularly in the red gastrocnemius muscle. Additionally, CBD prevented generation of lipid peroxidation products and attenuated inflammatory response in both types of skeletal muscle. In summary, the results mentioned above indicate that CBD presents potential therapeutic properties with respect to the treatment of obesity and related disturbances.

scholarly journals Picroside II Improves Severe Acute Pancreatitis-Induced Intestinal Barrier Injury by Inactivating Oxidative and Inflammatory TLR4-Dependent PI3K/AKT/NF-κB Signaling and Improving Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xuehua Piao ◽  
Baohai Liu ◽  
Xiaodan Sui ◽  
Shuangdi Li ◽  
Wei Niu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Gut Microbiota ◽  
Severe Acute Pancreatitis ◽  
Rat Model ◽  
Intestinal Barrier ◽  
Oxidative Stress Marker ◽  
Inflammatory Signaling ◽  
Picroside Ii ◽  
Anti Inflammatory

Background. Picroside II exerts anti-inflammatory and antidiarrheal effects for treating the diseases associated with oxidative injury. However, its function on pancreatitis-induced intestinal barrier injury remains unclear. Hypothesis/Purpose. We hypothesized that picroside II will have protective effects against pancreatitis-induced intestinal barrier injury by affecting oxidative and inflammatory signaling (Toll-like receptor 4- (TLR4-) dependent phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and nuclear factor kappa B (NF-κB)). Study Design and Methods. A Sprague-Dawley (SD) rat model with severe acute pancreatitis (SAP) was induced via the injection of sodium taurocholate (4% wt/vol; 1 mL/kg). All rats were divided into 3 groups: sham (CG), SAP-induced intestinal barrier injury (MG), and picroside II (PG) groups. Intestinal barrier injury was assessed by scanning electron microscopy (SEM), hematoxylin and eosin staining, and pathological scores. We measured the levels of pancreatitis biomarkers (amylase and lipase), oxidative and inflammatory signaling (TLR4-dependent PI3K/AKT/NF-κB), oxidative stress marker (superoxidase dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx), and malondialdehyde), and inflammatory markers (tumor necrosis factor α (TNFα), interleukin- (IL-) 1, IL-6, and IL-10) in serum and/or gut tissues. Gut microbiota composition in feces was measured by using 16S rRNA sequencing. Results. SEM showed that intestinal barrier injury was caused with the loss of intestinal villi and mitochondria destruction, and pathological scores were increased in the MG group. The levels of amylase, lipase, malondialdehyde, TNFα, IL-1, IL-6, TLR4, PI3K, AKT, and NF-κB were increased, and the levels of SOD, GPx, CAT, and IL-10 was reduced in the MG group when compared with CG group (P<0.05). Picroside II treatment inhibited the symptoms in the MG group and showed antioxidant and anti-inflammatory activities. The serum levels of picroside II had strong correlation with the levels of inflammatory and oxidative stress biomarkers (P<0.05). Picroside II treatment increased the proportion of Lactobacillus and Prevotella and decreased the proportion of Helicobacter and Escherichia_Shigella in the model. Conclusions. Picroside II improved the SAP-induced intestinal barrier injury in the rat model by inactivating oxidant and inflammatory signaling and improving gut microbiota.

scholarly journals Qingyi decoction attenuates severe acute pancreatitis in rats via inhibition of inflammation and protection of the intestinal barrier

2019 ◽  
Vol 47 (5) ◽  
pp. 2215-2227 ◽  
Author(s):  
Song Su ◽  
Tiancheng Liang ◽  
Xiang Zhou ◽  
Kai He ◽  
Bo Li ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Sodium Taurocholate ◽  
Intestinal Barrier ◽  
Pancreatic Tissue ◽  
Small Intestinal Mucosa ◽  
Barrier Dysfunction ◽  
Ileal Mucosa ◽  
Inflammatory Infiltration ◽  
Tnf Α

Objective Qingyi decoction (QYD) has beneficial effects in severe acute pancreatitis (SAP). We assessed the therapeutic effect and mechanisms of QYD in SAP. Methods A rat model of SAP was induced by pancreatic ductal injection of sodium taurocholate. QYD was administered intragastrically immediately postoperatively and once every 12 hours. Serum amylase, endotoxin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-lactate levels were measured at 12, 24, and 48 hours. Histological changes in the pancreas and ileum were analyzed. Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. Results Pancreatic tissue showed extracellular space expansion, inflammatory infiltration, vessels with necrotic walls, and hemorrhage. Ileal tissue showed hemorrhage, inflammatory infiltration, and ileal mucosa destruction. These histological features were dramatically improved by QYD. Increased serum levels of amylase, endotoxin, TNF-α, IL-6, and D-lactic acid were significantly decreased by QYD administration. Increased expression of NF-κB p65 and TLR4 and decreased expression of ZO-1 in the ileal mucosa were also restored to normal levels by QYD treatment. Conclusion QYD alleviates SAP by reducing intestinal barrier dysfunction, inhibiting intestinal bacteria and endotoxin translocation, and preventing NF-κB activation.

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