Nephroprotective effect of exogenous hydrogen sulfide donor against cyclophosphamide-induced toxicity is mediated by Nrf2/HO-1/NF-κB signaling pathway

Waz, Shaimaa; Heeba, Gehan H.; Hassanin, Soha Osama; Abdel‐latif, Rania G.

doi:10.1016/j.lfs.2020.118630

Cited by 38 publications

(33 citation statements)

References 51 publications

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“…50 HO-1 and NQO1 are the key downstream factors of Nrf2 signal transduction, which are very important in protecting cells from the oxidative damage. 51,52 Recent studies have shown that trimetazidine can delay the formation of age-related cataracts by regulating the expression of Nrf2 and reducing the production of ROS. 53 Whitson et al 54 found that LECs lacking glutathione (GSH) depend on the activation of the Nrf2 signaling pathway to trigger oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Echinatin mitigates H2O2-induced oxidative damage and apoptosis in lens epithelial cells via the Nrf2/HO-1 pathway

Ran¹,

Liu²,

Wu³

2021

Adv Clin Exp Med

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Background.Oxidative stress has been reported to be an early factor in the development of cataracts. Echinatin (Ech) is an active ingredient of licorice that exhibits antioxidant effects. Objectives.To investigate the effects of Ech on oxidative stress-induced lens epithelial cell (LEC) damage. Materials and methods.Human lens epithelial B3 cells (HLECs) were exposed to hydrogen peroxide (H 2 O 2 ) and were pretreated with or without Ech. For rescue experiments, ML385, an inhibitor of the Nrf2 pathway, was added into the medium.Results. Echinatin reversed the H 2 O 2 -induced reduction of cell viability in B3 cells. Additionally, H 2 O 2 induced oxidative stress, evidenced by an increase of reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and a decrease in superoxide dismutase (SOD) and catalase (CAT) levels, which could be abolished by Ech. Echinatin treatment also reduced HLEC apoptosis induced by H 2 O 2 . In addition, Ech pretreatment promoted Bcl-2 expression, and suppressed Bax and caspase-3 expression levels, in H 2 O 2 -treated B3 cells. Moreover, H 2 O 2 significantly reduced Nrf2 nuclear localization, as well as HO-1 and NQO1 expression, which could be reversed by Ech. Inhibition of Nrf2 by ML385 aggravated H 2 O 2 -induced oxidative damage and apoptosis in HLECs, and the protective effects of Ech on H 2 O 2 -induced oxidative damage and apoptosis could be restored by ML385. Conclusions.Echinatin mitigates H 2 O 2 -induced oxidative damage and apoptosis in HLECs via the Nrf2/HO-1 pathway, suggesting that Ech may be a potential drug for the treatment of cataracts.

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Section: Discussionmentioning

confidence: 99%

Echinatin mitigates H2O2-induced oxidative damage and apoptosis in lens epithelial cells via the Nrf2/HO-1 pathway

Ran¹,

Liu²,

Wu³

2021

Adv Clin Exp Med

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“… 2015 ; Waz et al. 2021 ). In our study, the mechanisms underlying the effects of HQH on apoptosis and inflammation were explored by examining apoptosis-related protein, the inflammatory cytokines and the inflammatory marker protein NF-κB.…”

Section: Discussionmentioning

confidence: 99%

“… 2020 ; Waz et al. 2021 ). The specific mechanisms of CYP-induced renal damage have been found to associate with oxidative stress, apoptosis and inflammation (Nagi et al.…”

Section: Introductionmentioning

confidence: 99%

Huaiqihuang (HQH) granule alleviates cyclophosphamide-induced nephrotoxicity via suppressing the MAPK/NF-κB pathway and NLRP3 inflammasome activation

Zhang

Chang

Gao

et al. 2021

Pharmaceutical Biology

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Context Severe nephrotoxicity greatly limits the clinical use of the common effective chemotherapeutic agent cyclophosphamide (CYP). Huaiqihuang (HQH) is a Chinese herbal complex with various pharmacological activities, widely used for treating kidney disease. Objective This study estimates the protective effect of HQH against CYP-induced nephrotoxicity in rats. Materials and methods Four groups of 10 Sprague-Dawley rats were pre-treated with once-daily oral gavage of 3 and 6 mg/kg HQH for 5 days before receiving a single dose of CYP (200 mg/kg i.p.) on the 5th day; the control group received equivalent dose of saline. Renal function indices, morphological changes, oxidative stress, apoptosis and inflammatory mediators were measured. In addition, phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were analysed. Results Both doses of HQH reduced the levels of serum creatinine (31.27%, 43.61%), urea nitrogen (22.66%, 32.27%) and urine protein (12.87%, 15.98%) in the CYP-treated rats, and improved histopathological aberrations. Additionally, HQH decreased the production of MDA (37.02%, 46.18%) and increased the activities of antioxidant enzyme CAT (59.18%, 112.25%) and SOD (67.10%, 308.34%) after CYP treatment. HQH protected against CYP-induced nephrotoxicity by modulating apoptosis-related protein and suppressing the inflammatory responses. Furthermore, the phosphorylation of the NF-κB/MAPK pathway and the activation of the NLRP3 inflammasome were significantly boosted in CYP-treated rats, which was also abrogated by HQH treatment. Conclusions HQH effectively protected against CYP-induced nephrotoxicity, which was associated with regulating oxidative stress, apoptosis and inflammation, and so HQH may be a useful agent for treating nephrotoxicity caused by CYP.

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“…It may also inhibit the production of ROS in cells by reducing the activity of NADPH oxidase. Recent studies have shown that exogenous H 2 S serves a renoprotective role in cyclophosphamide-induced nephrotoxicity, which is associated with increased expression of Nrf2 and downstream antioxidant proteins, such as heme oxygenase-1 (HO-1), and reduced glutathione and SOD in renal tissues ( 57 , 59 ), as shown in Fig. 4 .…”

Section: Role Of H 2 S In Renal Diseasementioning

confidence: 97%

Protective effect of hydrogen sulfide on the kidney (Review)

Zhang¹,

Zhao

Guo³

2021

Mol Med Rep

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Hydrogen sulfide (H 2 S) is a physiologically important gas transmitter that serves various biological functions in the body, in a manner similar to that of carbon monoxide and nitric oxide. cystathionine-β-synthase, cystathionine-γ-lyase and cysteine transaminase/3-mercaptopyruvate sulphotransferase are important enzymes involved H 2 S production in vivo, and the mitochondria are the primary sites of metabolism. it has been reported that H 2 S serves an important physiological role in the kidney. under disease conditions, such as ischemia-reperfusion injury, drug nephrotoxicity and diabetic nephropathy, H 2 S serves an important role in both the occurrence and development of the disease. The present review aimed to summarize the production, metabolism and physiological functions of H 2 S, and the progress in research with regards to its role in renal injury and renal fibrosis in recent years. Contents1. introduction 2. General physicochemical properties of H 2 S 3. Generation and metabolism of H 2 S 4. Physiological role of H 2 S in the kidney 5. role of H 2 S in renal disease 6. conclusions

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Nephroprotective effect of exogenous hydrogen sulfide donor against cyclophosphamide-induced toxicity is mediated by Nrf2/HO-1/NF-κB signaling pathway

Cited by 38 publications

References 51 publications

Echinatin mitigates H2O2-induced oxidative damage and apoptosis in lens epithelial cells via the Nrf2/HO-1 pathway

Echinatin mitigates H2O2-induced oxidative damage and apoptosis in lens epithelial cells via the Nrf2/HO-1 pathway

Huaiqihuang (HQH) granule alleviates cyclophosphamide-induced nephrotoxicity via suppressing the MAPK/NF-κB pathway and NLRP3 inflammasome activation

Protective effect of hydrogen sulfide on the kidney (Review)

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