Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice

Zhu, Qian; He, Guizhen; Wang, Jie; Wang, Yukang; Chen, Wei

doi:10.1038/srep22044

Cited by 24 publications

(20 citation statements)

References 33 publications

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“…The pathogenesis of intestinal I/R injury was found to be multifactorial and includes oxidative stress, inflammation, and intestinal epithelial barrier disruption, and emerging evidence has revealed that endogenous DAMPs (mtDNA) play a vital role in the initiation of I/R injury and remote organ injury 16 , 19 . However, none of the studies have illuminated the initiative role for mtDNA in intestinal I/R.…”

Section: Discussionmentioning

confidence: 99%

Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction

Ren

et al. 2018

Sci Rep

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Ischemia-reperfusion (I/R) injury is a challenging clinical problem, especially injuries involving the gastrointestinal tract. Mitochondrial DNA (mtDNA) is released upon cell death and stress, and can induce the inflammatory response. We aimed to investigate the role of mtDNA in the pathogenesis of intestinal I/R. Intestinal I/R model was established with clamping of the superior mesenteric artery, and IEC-6 cells were incubated under hypoxia/reoxygenation (H/R) conditions to simulate I/R injury. Using in vitro models, H/R up-regulated oxidative stress, disrupted mitochondrial activity and the mitochondrial membrane potential, induced apoptosis and elevated the mtDNA levels in the supernatant of intestinal epithelial cells, and the co-culture of mtDNA with human primary dendritic cells significantly elevated TLR9-MyD88 expression and enhanced the production of inflammatory cytokines and chemokines. MtDNA was also released in a mouse model of intestinal I/R and was associated with the increased secretion of inflammatory cytokines and increased gut barrier injury compared with that of the sham group. We concluded that mtDNA contributes to I/R injury and may serve as a biomarker of intestinal I/R. We further suggest that oxidized mtDNA originated from IECs during intestinal I/R exacerbates the acute proinflammatory process by eliciting the production of proinflammatory cytokines and chemokines.

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Section: Discussionmentioning

confidence: 99%

Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction

Ren

et al. 2018

Sci Rep

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“…Some studies confirm that lung I/R could induce sterile inflammatory eruption by activating the innate immune response 5 – 7 . The immune inflammatory reaction during lung I/R initiates by attracting inflammatory cells, such as lymphocytes, neutrophils, macrophages and releasing pro-inflammatory factors 8 .…”

Section: Introductionmentioning

confidence: 99%

Cobra Venom Factor-induced complement depletion protects against lung ischemia reperfusion injury through alleviating blood-air barrier damage

Chang

Wang

Huang

et al. 2018

Sci Rep

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The purpose of this study was to study whether complement depletion induced by pretreatment with Cobra Venom Factor (CVF) could protect against lung ischemia reperfusion injury (LIRI) in a rat model and explore its molecular mechanisms. Adult Sprague-Dawley rats were randomly assigned to five groups (n = 6): Control group, Sham-operated group, I/R group, CVF group, I/R + CVF group. CVF (50 μg/kg) was injected through the tail vein 24 h before anesthesia. Lung ischemia reperfusion (I/R) was induced by clamping the left hilus pulmonis for 60 minutes followed by 4 hours of reperfusion. Measurement of complement activity, pathohistological lung injury score, inflammatory mediators, pulmonary permeability, pulmonary edema, integrity of tight junction and blood-air barrier were performed. The results showed that pretreatment with CVF significantly reduced complement activity in plasma and BALF. Evaluation in histomorphology showed that complement depletion induced by CVF significantly alleviated the damage of lung tissues and inhibited inflammatory response in lung tissues and BALF. Furthermore, CVF pretreatment had the function of ameliorating pulmonary permeability and preserving integrity of tight junctions in IR condition. In conclusion, our results indicated that complement depletion induced by CVF could inhibit I/R-induced inflammatory response and alleviate lung I/R injury. The mechanisms of its protective effects might be ameliorated blood-air barrier damage.

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“…However, we demonstrated that CDDO-Im significantly decreased TNF-α production following I/R injury, and TNF-α has been verified to activate the apoptotic cascade through the death receptor/caspase pathway. 15 We therefore conclude that CDDO-Im attenuates apoptosis following intestinal I/R injury, at least in part, through an indirect manner.…”

Section: Discussionmentioning

confidence: 71%

Protective effect of CDDO-imidazolide against intestinal ischemia/reperfusion injury in mice

Huang

Wang

et al. 2018

Eur J Inflamm

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Intestinal ischemia/reperfusion (I/R) is life-threatening and challenging in clinical practice. CDDO-imidazolide (CDDO-Im) is therapeutic in alleviating I/R injury. Nevertheless, there is a lack of investigation on the effects of CDDO-Im on intestinal I/R. Mice were randomly divided into four groups: (a) the sham group, (b) the CDDO-Im group, (c) the I/R group, and (d) the I/R + CDDO-Im group. Intestinal I/R was performed by clamping arteria mesenteric anterior for 45 min, followed by 24 h reperfusion. In addition, Kaplan-Meier method and the log-rank test were used to compare the survival rates among groups by observing for 24 h. Intestinal I/R in model group demonstrated severe injury of the intestinal mucosa, lung, kidney, and liver. The intestinal mucosal damage and intestinal barrier dysfunction were obviously attenuated in CDDO-Im-treated group compared with the model group. Also, preconditioning with CDDO-Im reduced pulmonary, hepatic and renal damage, and decreased oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), and NO) and pro-inflammatory responses (tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6)) following I/R injury. Furthermore, we also observed that these protective properties of CDDO-Im were accomplished by the activation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway and upregulation of its downstream antioxidant genes, including heme oxygenase (HO-1), NQO-1, and glutamate-cysteine ligase regulatory subunit (GCLM). Our data suggest that CDDO-Im exerts a beneficial effect on intestinal I/R-associated mucosal barrier dysfunction and distant organ injuries.

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Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice

Cited by 24 publications

References 33 publications

Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction

Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction

Cobra Venom Factor-induced complement depletion protects against lung ischemia reperfusion injury through alleviating blood-air barrier damage

Protective effect of CDDO-imidazolide against intestinal ischemia/reperfusion injury in mice

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