Quercetin protects mouse liver against nickel-induced DNA methylation and inflammation associated with the Nrf2/HO-1 and p38/STAT1/NF-κB pathway

Liu, Chan-Min; Ma, Jie-Qiong; Xie, Wenli; Liu, Sisi; Zhao-jun, Feng; Zheng, Gui‐Hong; Ai-min, Wang

doi:10.1016/j.fct.2015.05.001

Cited by 112 publications

(50 citation statements)

References 42 publications

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“…Those results indicate that quercetin prevents TSN-induced hepatotoxicity via attenuation of liver oxidative injury by enhancing Nrf2-mediated GCLC/GCLM expression and subsequent GSH biosynthesis. Previous studies have already demonstrated that quercetin can prevent various hepatotoxicant-induced liver oxidative injuries by inducing Nrf2 activation [23,[27][28][29]. This study further confirmed the critical protective role of Nrf2 involved in this quercetinprovided hepatoprotective effect.…”

Section: Discussionsupporting

confidence: 84%

“…Our previous in vitro study showed that quercetin reversed TSN-induced cytotoxicity in human normal liver L-02 cells [27], indicating the potential detoxification of quercetin against TSN-induced liver injury. Moreover, some reports demonstrated that the hepatoprotective effects of quercetin were due to Nrf2 activation [23,[27][28][29]. In this study, whether quercetin can alleviate TSN-induced liver injury by inducing Nrf2 activation was also studied, which will be helpful to further confirm the critical protective role of Nrf2 in TSN-induced hepatotoxicity.…”

Section: Introductionmentioning

confidence: 79%

“…Quercetin is a natural flavonoid with well-known antioxidant capacity [20]. Quercetin has been reported to alleviate liver injury induced by various hepatotoxicants, including pyrrolizidine alkaloids, nickel, lipopolysaccharides/D-galactosamine, triptolide, and carbon tetrachloride [21][22][23][24][25][26]. Our previous in vitro study showed that quercetin reversed TSN-induced cytotoxicity in human normal liver L-02 cells [27], indicating the potential detoxification of quercetin against TSN-induced liver injury.…”

Section: Introductionmentioning

confidence: 99%

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Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway

Yao

Huang

et al. 2018

Acta Pharmacol Sin

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Toosendanin (TSN) is the main active compound in Toosendan Fructus and Meliae Cortex, two commonly used traditional Chinese medicines. TSN has been reported to induce hepatotoxicity, but its mechanism remains unclear. In this study, we demonstrated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2) in protecting against TSN-induced hepatotoxicity in mice and human normal liver L-02 cells. In mice, administration of TSN (10 mg/kg)-induced acute liver injury evidenced by increased serum alanine/aspartate aminotransferase (ALT/AST) and alkaline phosphatase (ALP) activities, and total bilirubin (TBiL) content as well as the histological changes. Furthermore, TSN markedly increased liver reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased liver glutathione (GSH) content and Nrf2 expression. In L-02 cells, TSN (2 μM) time-dependently reduced glutamate-cysteine ligase (GCL) activity and cellular expression of the catalytic/modify subunit of GCL (GCLC/GCLM). Moreover, TSN reduced cellular GSH content and the increased ROS formation, and time-dependently decreased Nrf2 expression and increased the expression of the Nrf2 inhibitor protein kelch-like ECH-associated protein-1 (Keap1). Pre-administration of quercetin (40, 80 mg/kg) effectively inhibited TSN-induced liver oxidative injury and reversed the decreased expression of Nrf2 and GCLC/GCLM in vivo and in vitro. In addition, the quercetin-provided protection against TSN-induced hepatotoxicity was diminished in Nrf2 knock-out mice. In conclusion, TSN decreases cellular GSH content by reducing Nrf2-mediated GCLC/GCLM expression via decreasing Nrf2 expression. Quercetin attenuates TSN-induced hepatotoxicity by inducing the Nrf2/GCL/GSH antioxidant signaling pathway. This study implies that inducing Nrf2 activation may be an effective strategy to prevent TSN-induced hepatotoxicity.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway

Yao

Huang

et al. 2018

Acta Pharmacol Sin

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“…Bilirubin and CO are metabolites/products of the HO-1 catalyzed cleavage of the porphyrin ring of heme and additionally both display anti-inflammatory effects protecting against experimental colitis in mice [ 138 , 139 , 140 , 141 , 142 ]. The activation of Nrf2 and the induction of HO-1 expression by the flavonoid quercetin also repressed the expression of NFκB and pro-inflammatory markers in the livers of nickel-treated mice [ 143 ]. Moreover, in LPS-activated macrophages and septic mice, an induction of HO-1 inhibited the expression of pro-inflammatory mediators through Nrf2 activation and NFκB inhibition [ 144 ].…”

Section: The Nrf2-nfκb Cross-talkmentioning

confidence: 99%

Brassica-Derived Plant Bioactives as Modulators of Chemopreventive and Inflammatory Signaling Pathways

Sturm

Wagner

2017

IJMS

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A high consumption of vegetables belonging to the Brassicaceae family has been related to a lower incidence of chronic diseases including different kinds of cancer. These beneficial effects of, e.g., broccoli, cabbage or rocket (arugula) intake have been mainly dedicated to the sulfur-containing glucosinolates (GLSs)—secondary plant compounds nearly exclusively present in Brassicaceae—and in particular to their bioactive breakdown products including isothiocyanates (ITCs). Overall, the current literature indicate that selected Brassica-derived ITCs exhibit health-promoting effects in vitro, as well as in laboratory mice in vivo. Some studies suggest anti-carcinogenic and anti-inflammatory properties for ITCs which may be communicated through an activation of the redox-sensitive transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) that controls the expression of antioxidant and phase II enzymes. Furthermore, it has been shown that ITCs are able to significantly ameliorate a severe inflammatory phenotype in colitic mice in vivo. As there are studies available suggesting an epigenetic mode of action for Brassica-derived phytochemicals, the conduction of further studies would be recommendable to investigate if the beneficial effects of these compounds also persist during an irregular consumption pattern.

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“…Treatment with caffeic acid (3,4dihydroxycinnamic acid) or chlorogenic acid [106] of hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cell lines partially inhibited the methylation of promoter region of the RARβ gene, thereby restoring its function [107]. Furthermore, studies also indicated that dietary antioxidants such as genistein, quercetin, parthenolide, and lycopene may affect DNA methylation status of different genes associated with cancer [108][109][110][111].…”

Section: Natural Compounds As Pharmacological Antioxidantsmentioning

confidence: 99%

Natural Compound-Generated Oxidative Stress: From Bench to Bedside

Mazumder¹,

Diederich²

2016

Free Radicals and Diseases

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Oxidants are constantly generated in a biological system as a result of physiological processes. However, an imbalance between oxidants and antioxidants can lead to a pathophysiological condition known as oxidative stress. Natural compounds as inducers of oxidative stress are able to modulate physiological functions of cancer cells leading to cell death or survival. This chapter aims at providing an overview of proand antioxidant activities of natural compounds related to cancer and related therapies.

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Quercetin protects mouse liver against nickel-induced DNA methylation and inflammation associated with the Nrf2/HO-1 and p38/STAT1/NF-κB pathway

Cited by 112 publications

References 42 publications

Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway

Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway

Brassica-Derived Plant Bioactives as Modulators of Chemopreventive and Inflammatory Signaling Pathways

Natural Compound-Generated Oxidative Stress: From Bench to Bedside

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