Amelioration of Coagulation Disorders and Inflammation by Hydrogen-Rich Solution Reduces Intestinal Ischemia/Reperfusion Injury in Rats through NF-κB/NLRP3 Pathway

Intestinal ischemia/reperfusion (I/R) injury often causes inflammatory responses and coagulation disorders, which is further promoting the deterioration of the disease. Hydrogen has anti-inflammatory, antioxidative, and antiapoptotic properties against various diseases. However, the effect of hydrogen on coagulation dysfunction after intestinal I/R and the underlying mechanism remains unclear. The purpose of this study was to explore whether hydrogen-rich solution (HRS) could attenuate coagulation disorders and inflammation to improve intestinal injury and poor survival following intestinal I/R. The rat model of intestinal I/R injury was established by clamping the superior mesenteric artery for 90 min and reperfusion for 2 h. HRS (10 or 20 mL/kg) or 20 mL/kg 0.9% normal saline was intravenously injected at 10 min before reperfusion, respectively. The samples were harvested at 2 h after reperfusion for further analyses. Moreover, the survival rate was observed for 24 h. The results showed that HRS improved the survival rate and alleviated serum diamine oxidase activities, intestinal injury, edema, and apoptosis. Interestingly, HRS markedly improved intestinal I/R-mediated coagulation disorders as evidenced by abnormal conventional indicators of coagulation and thromboelastography. Additionally, HRS attenuated inflammatory responses and the elevated tissue factor (TF) and inhibited nuclear factor kappa beta (NF-κB) and nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation in peripheral blood mononuclear cells. Moreover, inflammatory factors and myeloperoxidase were closely associated with TF level. This study thus emphasized upon the amelioration of coagulation disorders and inflammation by HRS as a mechanism to improve intestinal I/R-induced intestinal injury and poor survival, which might be partially related to inhibition of NF-κB/NLRP3 pathway.

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Resveratrol Suppresses Gut-Derived NLRP3 Inflammasome Partly through Stabilizing Mast Cells in a Rat Model

Mediators of Inflammation ◽

10.1155/2018/6158671 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Weicheng Zhao ◽

Xiaolei Huang ◽

Xue Han ◽

Dan Hu ◽

Xiaohuai Hu ◽

...

Keyword(s):

Mast Cells ◽

Proinflammatory Cytokines ◽

Nlrp3 Inflammasome ◽

Intestinal Ischemia ◽

Inflammatory Responses ◽

Ischemia Reperfusion ◽

Interleukin 1 ◽

Intestinal Injury ◽

Cromolyn Sodium ◽

Inflammasome Activation

Background. Inflammatory responses induced by intestinal ischemia-reperfusion (IIR) lead to serious systemic organ dysfunction and pose a challenge for current treatment. This study aimed at investigating the effects of resveratrol on IIR-induced intestinal injury and its influence on mast cells (MCs) in rats. Methods. Rats subjected to intestinal ischemia for 60 min and 4 h of IIR were investigated. Animals were randomly divided into five groups (n=8 per group): sham, IIR, resveratrol (RESV, 15 mg/kg/day for 5 days before operation) + IIR, cromolyn sodium (CS, MC membrane stabilizer) + IIR, and RESV + compound 48/80 (CP, MC agonist) + IIR. Results. Intestinal injury and increased proinflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-18 were observed in the IIR group. Intestinal MC-related tryptase and β-hexosaminidase levels were also increased after rats were subjected to IIR accompanied by activation of NLRP3 inflammasomes. Interestingly, pretreatment with resveratrol significantly suppressed the activities of proinflammatory cytokines and attenuated intestinal injury. Resveratrol also reduced MC and NLRP3 inflammasome activation, which was consistent with the effects of cromolyn sodium. However, the protective effects of resveratrol were reversed by the MC agonist compound 48/80. Conclusions. In summary, these findings reveal that resveratrol suppressed IIR injury by stabilizing MCs, preventing them from degranulation, accompanied with intestinal mucosa NLRP3 inflammasome inhibition and intestinal epithelial cell apoptosis reduction.

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Autophagy Induction Ameliorates Inflammatory Responses in Intestinal Ischemia–Reperfusion Through Inhibiting NLRP3 Inflammasome Activation

Shock ◽

10.1097/shk.0000000000001259 ◽

2019 ◽

Vol 52 (3) ◽

pp. 387-395 ◽

Cited By ~ 6

Author(s):

Zishuo Wang ◽

Zhenlu Li ◽

Dongcheng Feng ◽

Guo Zu ◽

Yang Li ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Intestinal Ischemia ◽

Inflammatory Responses ◽

Ischemia Reperfusion ◽

Inflammasome Activation ◽

Nlrp3 Inflammasome Activation ◽

Autophagy Induction ◽

Intestinal Ischemia Reperfusion

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Irisin Contributes to the Hepatoprotection of Dexmedetomidine during Intestinal Ischemia/Reperfusion

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7857082 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 6

Author(s):

Xin Fan ◽

Juan Du ◽

Mao-Hua Wang ◽

Jia-Man Li ◽

Bo Yang ◽

...

Keyword(s):

Liver Injury ◽

Nlrp3 Inflammasome ◽

Intestinal Ischemia ◽

Ischemia Reperfusion ◽

Neutralizing Antibody ◽

Inflammasome Activation ◽

High Morbidity ◽

Antibody Treatment ◽

Sod Activity ◽

Intestinal Ischemia Reperfusion

Intestinal ischemia/reperfusion (I/R), which is associated with high morbidity and mortality, is also accompanied with abnormal energy metabolism and liver injury. Irisin, a novel exercise-induced hormone, can regulate adipose browning and thermogenesis. The following study investigated the potential role of dexmedetomidine in liver injury during intestinal I/R in rats. Adult male Sprague–Dawley rats underwent occlusion of the superior mesenteric artery for 90 min followed by 2 h of reperfusion. Dexmedetomidine or irisin-neutralizing antibody was intravenously administered for 1 h before surgery. The results demonstrated that severe intestine and liver injuries occurred during intestinal I/R as evidenced by pathological scores and an apparent increase in serum diamine oxidase (DAO), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels. In addition, the hepatic irisin, cleaved caspase-3, Bax, and NLRP3 inflammasome components (including NLRP3, ASC, and caspase-1), protein expressions, apoptotic index, reactive oxygen species (ROS), malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 levels increased; however, the serum irisin level and hepatic Bcl-2 protein expression and superoxide dismutase (SOD) activity decreased after intestinal I/R. Interestingly, dexmedetomidine could reduce the above listed changes and increase the irisin levels in plasma and the liver in I/R rats. Dexmedetomidine-mediated protective effects on liver injury and NLRP3 inflammasome activation during intestinal I/R were partially abrogated via irisin-neutralizing antibody treatment. The results suggest that irisin might contribute to the hepatoprotection of dexmedetomidine during intestinal ischemia/reperfusion.

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Pharmacological enrollment of aldehyde dehydrogenase modulators to assist treating ischemia reperfusion-induced intestinal injury: is there a gap to be bridged?

Clinical Science ◽

10.1042/cs20170163 ◽

2017 ◽

Vol 131 (11) ◽

pp. 1137-1140 ◽

Cited By ~ 1

Author(s):

Laurent Dollé

Keyword(s):

Protective Effect ◽

Aldehyde Dehydrogenase ◽

Small Molecule ◽

Intestinal Ischemia ◽

Ischemia Reperfusion ◽

Clinical Science ◽

Intestinal Injury ◽

Intestinal Ischemia Reperfusion ◽

Near Future

This commentary highlights the research presented by Zhu et al. [1]. In this issue of the Clinical Science, the authors evaluated the protective effect of Alda-1 (a novel class of small molecule aldehyde dehydrogenase (ALDH2) activators) in the intestinal ischemia reperfusion (IR) injury. Remarkably, enhancing the ADLH2 activity by the use of Alda-1 can ameliorate several deleterious effects related to aldehydes, and may provide a better protection against an injury preestablished by IR. Together, an innovative metabolic strategy for treating patients with IR injury could be the use of ALDH modulators in a near future.

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Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

Mediators of Inflammation ◽

10.1155/2015/792016 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Ozkan Onal ◽

Fahri Yetisir ◽

A. Ebru Salman Sarer ◽

N. Dilara Zeybek ◽

C. Oztug Onal ◽

...

Keyword(s):

Reperfusion Injury ◽

Intestinal Ischemia ◽

Ischemia Reperfusion Injury ◽

Tissue Injury ◽

Ischemia Reperfusion ◽

Intestinal Injury ◽

Control Group ◽

Injury Score ◽

Tissue Samples ◽

Intestinal Ischemia Reperfusion

Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine.Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test.Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group.Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation.

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Translocation of 99mTc labelled bacteria after intestinal ischemia and reperfusion

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502004000400003 ◽

2004 ◽

Vol 19 (4) ◽

pp. 328-333 ◽

Cited By ~ 7

Author(s):

Samir Assi João ◽

Suelene Suassuna Silvestre de Alencar ◽

Aldo da Cunha Medeiros ◽

Simone Otília Fernandes Diniz ◽

Valbert Nascimento Cardoso ◽

...

Keyword(s):

Bacterial Translocation ◽

Intestinal Ischemia ◽

Inflammatory Responses ◽

Ischemia Reperfusion ◽

Ischemia And Reperfusion ◽

Mesenteric Lymph Nodes ◽

Mesenteric Lymph ◽

Colony Forming Units ◽

Male Wistar Rats ◽

Intestinal Ischemia Reperfusion

PURPOSE: Ischemia and reperfusion of the small intestine disrupts gut barrier, causes bacterial translocation and activates inflammatory responses. An experimental study was planned to evaluate if 99mTc labelled Escherichia coli translocates to mesenteric lymph nodes, liver, spleen, lung and serum of rats submitted to mesenteric ischemia/reperfusion. Additionally, it was observed if the time of reperfusion influences the level of translocation. METHODS: Forty male Wistar rats underwent 45 minutes of gut ischemia by occlusion of the superior mesenteric artery. The translocation of labelled bacteria to different organs and portal serum was determined in rats reperfused for 30 minutes, 24 hours, sham(S) and controls(C), using radioactivity count and colony forming units/g (CFU). RESULTS: All the organs from rats observed for 24 hours after reperfusion had higher levels of radioactivity and positive cultures (CFU) than did the organs of rats reperfused for 30 minutes, C and S, except in the spleen (p<0,01). CONCLUSION: The results of this study indicated that intestinal ischemia/reperfusion led to bacterial translocation, mostly after 24 hours of reperfusion.

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Nicaraven Attenuates Postoperative Systemic Inflammatory Responses-Induced Tumor Metastasis

Annals of Surgical Oncology ◽

10.1245/s10434-019-08076-2 ◽

2019 ◽

Vol 27 (4) ◽

pp. 1068-1074 ◽

Cited By ~ 2

Author(s):

Xu Zhang ◽

Takahito Moriwaki ◽

Tsuyoshi Kawabata ◽

Shinji Goto ◽

Ke-Xiang Liu ◽

...

Keyword(s):

Cancer Cells ◽

Tumor Metastasis ◽

Intestinal Ischemia ◽

Cancer Metastasis ◽

Inflammatory Responses ◽

Ischemia Reperfusion ◽

Inflammatory Cells ◽

Major Surgery ◽

Lewis Lung Cancer ◽

Intestinal Ischemia Reperfusion

Abstract Background Inflammation has been demonstrated to promote cancer metastasis. Due to the well-known systemic inflammatory responses (SIR) after major surgery, it is critical to investigate and attenuate SIR-induced tumor metastasis of cancer patients suffering surgical procedures. Methods C57BL/6 mice were intravenously injected with Lewis lung cancer cells at 6, 24, and 72 h after the induction of intestinal ischemia/reperfusion (I/R) injury. We found that the number of tumor nodules significantly increased in lungs of mice injected with cancer cells at 6 h but not at 24 and 72 h after I/R injury. The administration of nicaraven 30 min before and 24 h after I/R injury effectively attenuated the enhanced tumor metastasis to lungs. Protein array showed the increase of various cytokines in plasma of mice at 6 h after I/R injury, but many of them were attenuated by the administration of nicaraven. Immunostaining indicated the increase of Ly6g-, CD206-, and CD11c-positive inflammatory cells in the lungs, but it was also attenuated by nicaraven administration. Conclusions Postoperative SIR-induced tumor metastasis have been clearly evidenced in our experimental model, and the administration of nicaraven may ameliorate the SIR-induced tumor metastasis by suppressing inflammatory responses.

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