Preconditioning with Physiological Levels of Ethanol Protect Kidney against Ischemia/Reperfusion Injury by Modulating Oxidative Stress

Yuan, Qing; Hong, Shanjuan; Han, Shu; Zeng, Li; Liu, Fang; Ding, Guoyu; Kang, Yindong; Mao, Jingyan; Cai, Ming; Zhu, Youhua; Wang, Quanxing

doi:10.1371/journal.pone.0025811

Cited by 51 publications

(37 citation statements)

References 44 publications

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“…Of these, the excessive generation of ROS causes damage and death of renal tubular epithelial cells [7]. The role of ROS in the pathophysiology of I/R injury is supported by increased formation of lipid peroxidation and other toxic products following renal injury [8, 9]. …”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway

Zhang

Wang

Zhou³

et al. 2016

Kidney Blood Press Res

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Background/Aims: Tempol is a protective antioxidant against ischemic injury in many animal models. The molecular mechanisms are not well understood. Nuclear factor erythroid 2-related factor (Nrf2) is a master transcription factor during oxidative stress, which is enhanced by activation of protein kinase C (PKC) pathway. Another factor, tubular epithelial apoptosis, is mediated by activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, Akt) signaling pathway during renal ischemic injury. We tested the hypothesis that tempol activates PKC or PI3K/Akt/Nrf2 pathways to transcribe many genes that coordinate endogenous antioxidant defense. Methods: The right renal pedicle was clamped for 45 minutes and the left kidney was removed to study renal ischemia/reperfusion (I/R) injury in C57BL/6 mice. The response was assessed from serum parameters, renal morphology and renal expression of PKC, phosphorylated-PKC (p-PKC), Nrf2, heme oxygenase-1 (HO-1), Akt, phosphorylated-Akt (p-Akt), pro-caspase-3 and cleaved caspase-3 in groups of sham and I/R mice given vehicle, or tempol (50 or 100 mg/kg, intraperitoneal injection). Results: The serum malondialdehyde (MDA, marker of reactive oxygen species) doubled and the BUN and creatinine increased 5- to 10-fold after I/R injury. Tempol (50 or 100 mg/kg) prevented the increases in MDA but only tempol (50 mg/kg) lessened the increases in BUN and creatinine and moderated the acute tubular necrosis. I/R did not change expression of PKC or p-PKC but reduced renal expression of Nrf2, p-Akt, HO-1 and pro-caspase-3 and increased cleaved caspase-3. Tempol (50 mg/kg) prevented these changes produced by I/R whereas tempol (100 mg/kg) had lesser or inconsistent effects. Conclusion: Tempol (50 mg/kg) prevents lipid peroxidation and attenuates renal damage after I/R injury. The beneficial pathway apparently is not dependent on upregulation or phosphorylation of PKC, at lower tempol doses, does implicate upregulation of Akt with expression of Nrf2 that could account for the increase in the antioxidant gene HO-1 and a reduction in the cleavage of the cellular damage marker pro-caspase-3.

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Section: Introductionmentioning

confidence: 99%

Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway

Zhang

Wang

Zhou³

et al. 2016

Kidney Blood Press Res

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“…Sepsis is associated with mitochondrial dysfunction and impaired oxygen consumption (16,17), ALDH2 is localized in the mitochondrial fraction, and mitochondrial dysfunction changes ALDH2 function. A number of studies have reported that ALDH2 protects against organ injury, such as that affecting the kidneys, heart and neurons (10,(18)(19)(20). Our previous studies showed that cardiac ALDH2 expression was decreased in rats with diabetes, or myocardial ischemia and reperfusion injury, and that upregulation of ALDH2 protected against myocardial injury and protected the lungs against diabetes-induced lung injury, all of which indicate that ALDH2 could be an intrinsic factor regulating the occurrence of disease (12,21,22).…”

Section: Discussionmentioning

confidence: 91%

“…With regard to the role of ALDH2 in the pathogenesis of sepsis, Chen et al reported that hepatic ALDH2 activity was downregulated in septic rats following cecal ligation and puncture (CLP) (9). It has been reported that preconditioning with ethanol to stimulate ALDH2 activity prevented kidney ischemia and reperfusion injury in mice (10); however, the role of renal ALDH2 in sepsis-induced AKI is unclear. It remains to be determined whether ALDH2 is also a key factor associated with kidney injury.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of ALDH2 expression aggravates renal injury in a rat sepsis syndrome model

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is closely associated with organ injury. The aim of the present study was to investigate the change of ALDH2 expression in a rat model of sepsis-induced acute renal injury, and to observe the effect of ALDH2 inhibition on the kidney. A model of sepsis syndrome was established in Sprague-Dawley (SD) rats by cecal ligation and puncture (CLP). The rats were divided into sham, CLP and CLP + cyanamide (CYA, an ALDH2 inhibitor) groups. The hemodynamic parameters heart rate (HR) and mean arterial blood pressure (MABP) were measured. Plasma creatinine (CRE) and urea nitrogen (BUN) levels were measured using an automatic biochemical analyzer. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the kidney tissue were measured. Histological changes of the kidney tissue were observed using hematoxylin and eosin staining and NF-κB p65 expression was observed by an immunohistochemical staining method. The expression of renal ALDH2 at the mRNA and protein levels was detected by reverse transcription-polymerase chain reaction and western blotting. In the CLP compared with the sham group after 24 h, the MABP was decreased, plasma CRE and BUN levels were elevated, the renal MDA level was increased and SOD activity was decreased. In addition, glomerular atrophy occurred, the renal protein expression of NF-κB p65 was increased, and the mRNA and protein expression levels of ALDH2 were decreased. In contrast with the CLP group, in the CLP + CYA group, the MABP and ALDH2 expression were further decreased while glomerular atrophy was aggravated. Furthermore, CRE, BUN, MDA levels and NF-κB p65 expression were further increased and SOD activity was further reduced. In this rat model of sepsis syndrome, the reduction of renal ALDH2 expression was accompanied by kidney injury. Inhibition of ALDH2 with CYA aggravated the renal injury, and was associated with the overproduction of reactive oxygen species and inflammatory reaction.

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“…Indeed, a study performed on mice showed that moderate antecedent ethanol exposure provides protection for the kidneys against subsequent IR-induced injury 17 . In contrast, ethanol (1.9%) was shown to have a tendency to increase superoxide anion production in a model of cold preservation-warm reperfusion liver injury and this effect was detected to be reversed by the application of silibinin in a previous study 5 .…”

Section: Resultsmentioning

confidence: 99%

Effects of silibinin and ethanol on skeletal muscle ischemia-reperfusion injury

et al. 2013

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PURPOSE:To investigate the potential beneficial effect of silibinin in ischemia-reperfusion injury (IRI) of skeletal muscle. METHODS: Under urethane anesthesia, four experimental groups were established in Balb/c mice: I) Sham-control, II) IRI (Tourniquet-induced) (2+1 h), III) IRI+ethanol (10%), and IV) IRI+silibinin (50 mg/kg/IP). The viability of muscle (left) was evaluated by the triphenyltetrazolium chloride dye method and calculated as the percentage of the contralateral control muscle (right). Malondialdehyde, superoxide dismutase, and catalase were measured in the gastrocnemius muscle via a spectrophotometer. RESULTS:The viability of gastrocnemius muscle in group II was significantly lower in comparison with that seen in group I. The administration of either ethanol or silibinin rendered the tissues to recover nearly to the baseline level. Additionally, malondialdehyde levels were higher in group II than those in group I. The application of silibinin prior to the reperfusion attenuated these to the control levels. However, malondialdehyde levels in the ethanol administrated group were reduced as well. The enhanced superoxide dismutase activity seen in the IRI group was not diminished in the animals treated with either silibinin or ethanol. Similarly, there were no differences between groups regarding the catalase activities. CONCLUSION: Ethanol seems to be effective in attenuating IRI in skeletal muscle and no definite conclusion can be made on silibinin effect.

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Preconditioning with Physiological Levels of Ethanol Protect Kidney against Ischemia/Reperfusion Injury by Modulating Oxidative Stress

Cited by 51 publications

References 44 publications

Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway

Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway

Inhibition of ALDH2 expression aggravates renal injury in a rat sepsis syndrome model

Effects of silibinin and ethanol on skeletal muscle ischemia-reperfusion injury

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