Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation  in Rats

Wang, Peng; Huang, Jen-Fa; Li, Yi; Chang, Ruiming; H, Wu; Lin, Jie; Huang, Zitong

doi:10.3390/ijms160920595

Cited by 64 publications

(43 citation statements)

References 38 publications

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“…In recent years, several animal experiments showed that massive inflammatory cells infiltration and renal tubular epithelial cells apoptosis could be observed at 24 hours after CLP [26–28]. In our study, only sporadic inflammatory cells infiltration were found around glomerulus at 12 hours after CLP, suggesting that inflammatory response mediated by inflammatory cells might not play a leading role at the early stage of sepsis-induced AKI.…”

Section: Discussioncontrasting

confidence: 46%

Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway

Wang

Liu

et al. 2017

Oncotarget

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Resveratrol, a polyphenol compound derived from various edible plants, protects against sepsis-induced acute kidney injury (AKI) via its anti-inflammatory activity, but the underlying mechanisms remain largely unknown. In this study, a rat model of sepsis was established by cecal ligation and puncture (CLP), 30 mg/kg resveratrol was intraperitoneally administrated immediately after the CLP operation. HK-2 cells treated by 1 μg/ml lipopolysaccharide, 0.2 μM tunicamycin, 2.5 mM irestatin 9389 and 20 μM resveratrol were used for in vitro study. The results demonstrated that resveratrol significantly improved the renal function and tubular epithelial cell injury and enhanced the survival rate of CLP-induced rat model of sepsis, which was accompanied by a substantial decrease of the serum content and renal mRNA expressions of TNF-α, IL-1β and IL-6. In addition, resveratrol obviously relieved the endoplasmic reticulum stress, inhibited the phosphorylation of inositol-requiring enzyme 1(IRE1) and nuclear factor-κB (NF-κB) in the kidney. In vitro studies showed that resveratrol enhanced the cell viability, reduced the phosphorylation of NF-κB and production of inflammatory factors in lipopolysaccharide and tunicamycin-induced HK-2 cells through inhibiting IRE1 activation. Taken together, administration of resveratrol as soon as possible after the onset of sepsis could protect against septic AKI mainly through inhibiting IRE1-NF-κB pathway-triggered inflammatory response in the kidney. Resveratrol might be a readily translatable option to improve the prognosis of sepsis.

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Section: Discussioncontrasting

confidence: 46%

Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway

Wang

Liu

et al. 2017

Oncotarget

View full text Add to dashboard Cite

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“…Previous studies have suggested that oxidative stress directly or indirectly elevates inflammatory responses ( 21 , 23 , 24 ). Therefore, serum TNF-α, IL-1β and IL-6 levels were measured at 24 h after CLP surgery.…”

Section: Resultsmentioning

confidence: 99%

“…2A ). It is well known that AKI is a serious complication in septic rats, and BUN and Scr are frequently used as biomarkers in the early stages of the development of AKI ( 21 ). In the present study, BUN and Scr levels were measured at 24 h after CLP surgery to evaluate renal function in septic mice.…”

Section: Resultsmentioning

confidence: 99%

Oral supplementation with ursolic acid ameliorates sepsis-induced acute kidney injury in a mouse model by inhibiting oxidative stress and inflammatory responses

Zhang

Chen

et al. 2018

Mol Med Report

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Ursolic acid (UA) as a multiple bioactive native compound has recently been demonstrated to treat sepsis in animal models. However, the beneficial effects of UA in sepsis-induced acute kidney injury (AKI) are not completely understood. In the present study, the effect of UA on sepsis-induced AKI in cecal ligation and puncture (CLP) surgery mice was investigated. Renal histomorphological analysis was performed by hematoxylin and eosin staining. The expression of inflammatory markers in the kidney of septic mice was measured by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that UA administration improved survival in septic mice induced by CLP surgery. The treatment with UA revealed protection against AKI induced by CLP surgery, including the alleviation of glomerular damage and vacuolization in the proximal tubules. In addition, the effects of UA on oxidative stress and inflammation in septic mice were determined. The findings suggested that UA may protect against sepsis-induced AKI by inhibiting reactive oxygen species and inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β and IL-6, in the kidney from septic mice. Finally, UA inhibited CLP-induced activation of nuclear factor-κB signaling in the kidney from septic mice. The findings of the present study demonstrated that UA may be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI.

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“…Other anti‐inflammatory effects include increases in phospho‐p38 MAPK and phospho‐Akt as well as decreases in innate immune TLR4 signaling and TLR4 trafficking to the cell membrane surface . CO also inhibits NLRP3 inflammasome activation . Fifth, NO bioavailability is decreased in SCD.…”

Section: Overview Of Potential Carbon Monoxide Actions In Sickle Cellmentioning

confidence: 99%

The role of carbon monoxide and heme oxygenase in the prevention of sickle cell disease vaso‐occlusive crises

et al. 2017

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Sickle Cell Disease (SCD) is a painful, lifelong hemoglobinopathy inherited as a missense point mutation in the hemoglobin (Hb) beta‐globin gene. This disease has significant impact on quality of life and mortality, thus a substantial medical need exists to reduce the vaso‐occlusive crises which underlie the pathophysiology of the disease. The concept that a gaseous molecule may exert biological function has been well known for over one hundred years. Carbon monoxide (CO), although studied in SCD for over 50 years, has recently emerged as a powerful cytoprotective biological response modifier capable of regulating a host of physiologic and therapeutic processes that, at low concentrations, exerts key physiological functions in various models of tissue inflammation and injury. CO is physiologically generated by the metabolism of heme by the heme oxygenase enzymes and is measurable in blood. A substantial amount of preclinical and clinical data with CO have been generated, which provide compelling support for CO as a potential therapeutic in a number of pathological conditions. Data underlying the therapeutic mechanisms of CO, including in SCD, have been generated by a plethora of in vitro and preclinical studies including multiple SCD mouse models. These data show CO to have key signaling impacts on a host of metallo‐enzymes as well as key modulating genes that in sum, result in significant anti‐inflammatory, anti‐oxidant and anti‐apoptotic effects as well as vasodilation and anti‐adhesion of cells to the endothelium resulting in preservation of vascular flow. CO may also have a role as an anti‐polymerization HbS agent. In addition, considerable scientific data in the non‐SCD literature provide evidence for a beneficial impact of CO on cerebrovascular complications, suggesting that in SCD, CO could potentially limit these highly problematic neurologic outcomes. Research is needed and hopefully forthcoming, to carefully elucidate the safety and benefits of this potential therapy across the age spectrum of patients impacted by the host of pathophysiological complications of this devastating disease.

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Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats

Cited by 64 publications

References 38 publications

Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway

Resveratrol protects against early polymicrobial sepsis-induced acute kidney injury through inhibiting endoplasmic reticulum stress-activated NF-κB pathway

Oral supplementation with ursolic acid ameliorates sepsis-induced acute kidney injury in a mouse model by inhibiting oxidative stress and inflammatory responses

The role of carbon monoxide and heme oxygenase in the prevention of sickle cell disease vaso‐occlusive crises

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