Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation

Tsai, Pei-Yi; Ka, Shuk‐Man; Chang, Jia‐Ming; Hc, Chen; Shui, Hao‐Ai; Li, Chenyun; Hua, Kuo-Feng; Chang, Wen-Liang; Huang, Jow Lay; Yang, Sung-Sen; Chen, Ann

doi:10.1016/j.freeradbiomed.2011.05.016

Cited by 226 publications

(196 citation statements)

References 80 publications

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“…In contrast natural phytochemical Nrf2 activators such as sulforaphane, epigallocatechin-3-gallate, and curcumin, improve nephropathy in animal models of acute or chronic kidney diseases of diverse etiologies [19][20][21][22][23]. Together these observations support the role of Nrf2 deficiency in the pathogenesis of oxidative stress, inflammation, and progression of kidney disease.…”

Section: Introductionmentioning

confidence: 64%

“…Activation of these pathways confers protection by up-regulating expression of antioxidant enzymes, detoxifying compounds, protein chaperones, and trophic factors. In fact these phytochemicals have been shown to prevent or ameliorate a variety of diseases including cardiovascular disease [42,43], neurodegenerative disorders [44][45][46][47][48][49], and acute and chronic kidney disease [19][20][21][22][23]. In contrast, excessive or unrestrained activity of Nrf2 system has been shown to have adverse consequences.…”

Section: Discussionmentioning

confidence: 99%

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Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Vaziri¹,

Liu²,

Farzaneh³

et al. 2015

Free Radical Biology and Medicine

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Oxidative stress and inflammation play a central role in progression and complications of CKD and are, in part, due to impairment of the Nrf2 system which regulates expression of antioxidant and detoxifying molecules. Natural Nrf2 inducing phytochemicals have been shown to ameliorate kidney disease in experimental animals. However due to adverse outcomes clinical trial of synthetic Nrf2 activator, bardoxolone methyl (BARD), in CKD patients was terminated. BARD activates Nrf2 via 2 covalent modification of reactive cysteine residues in Nrf2 repressor molecule, Keap-1. In addition to Nrf2, Keap1 suppresses IKKB, the positive regulator of NF k B. Treatment with BARD analog, dh404, at 5-20 mg/kg/day in diabetic obese Zucker rats exacerbates whereas its use at 2 mg/kg/day in 5/6 nephrectomized rats attenuates CKD progression. We, therefore, hypothesized that deleterious effects of high dose BARD are mediated by activation of NF k B.CKD (5/6 nephrectomized) rats were randomized to receive dh404 (2 or 10mg/kg/day) or vehicle for 12 weeks. Vehicle-treated group exhibited glomerulosclerosis, interstitial fibrosis and inflammation, activation of NF k B, upregulation of oxidative, inflammatory and fibrotic pathways, and suppression of Nrf2 activity and its key target gene products. Treatment with low dose dh404 restored Nrf2 activity and expression of its target genes, attenuated activation of NF k B and fibrotic pathways, and reduced glomerulosclerosis, interstitial fibrosis and inflammation. In contrast treatment with high dh404 dosage intensified proteinuria, renal dysfunction and histological abnormalities, amplified up-regulations of NF k B and fibrotic pathways, and suppression of Nrf2 system. Thus therapy with BARD analogs exerts a dose-dependent dimorphic impact on CKD progression.

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Section: Introductionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Vaziri¹,

Liu²,

Farzaneh³

et al. 2015

Free Radical Biology and Medicine

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“…Nrf2 is essential for cholesterol crystal-induced inflammasome activation, 18 but epigallocatechin-3-gallate prevents lupus nephritis development via the up-regulation of the Nrf2 antioxidant pathway, which inhibits NLRP3 inflammasome activation. 19 The role of Nrf2 has been demonstrated to affect the NLRP3 inflammasome differently in cholesterol-induced atherosclerosis and lupus nephritis. 18,19 The role of Nrf2 in MSU-induced inflammation is similar to that observed with cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Monosodium urate crystals trigger Nrf2- and heme oxygenase-1-dependent inflammation in THP-1 cells

Jhang

Cheng

et al. 2014

Cell Mol Immunol

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Gouty arthritis is an inflammatory disease that is caused by an accumulation of monosodium urate (MSU) crystals in the joints. MSU is capable of activating the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome, leading to interleukin-1b (IL-1b) secretion. Reactive oxygen species (ROS) are major mediators of the NLRP3/IL-1b interaction. Although nuclear factor E2-related factor 2 (Nrf2) is recognized as a transcription factor that is involved in the response to oxidative stress, the effect of MSU on Nrf2 and on Nrf2-mediated antioxidant enzymes remains unclear. The treatment of THP-1 monocytes using phorbol 12-myristate 13-acetate (PMA) was shown to initiate inflammatory responses. Here, we showed that THP-1 cells, following treatment with MSU crystals, significantly increased IL-1b release, NLRP3 inflammasome activation and ROS production. MSU also promoted the nuclear translocation of Nrf2 and activated lysosomal destabilization. Moreover, the levels of heme oxygenase-1 (HO-1) in gene and protein expressions were upregulated by MSU. MSU-induced IL-1b secretion and NLRP3 inflammasome activation were inhibited by the knockdown of Nrf2 and via the HO-1 inhibitor zinc (II) protoporphyrin IX (ZnPP). In addition, HO-1 inhibition increased the level of superoxide anion production and the consumption of glutathione. These findings suggest that Nrf2 and HO-1 mediate redox homeostasis and interact with pro-inflammatory factors in MSU-challenged THP-1 cells, thereby providing new insight into how MSU-induced gouty inflammation is mediated by specific mechanisms that are involved in the Nrf2/Ho-1 antioxidant signaling pathway.

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“…This issue needs to be addressed. It is established that expression levels or the activity of HO-1 and GPx are involved in the elimination or inactivation of ROS [35], and that this effect is mediated by activation of NRF2 [36]. Although normal tissues express extremely low basal levels of HO-1 protein [37,38], diabetic rats receiving antioxidant treatment have significantly increased HO-1 protein levels compared with normal controls [39].…”

Section: Discussionmentioning

confidence: 99%

Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-κB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis

Yang¹,

Ka²,

et al. 2013

Diabetologia

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100

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Aims/hypothesis Chronic inflammatory processes have been increasingly shown to be involved in the pathogenesis of diabetes and diabetic nephropathy. Recently, we demonstrated that a lectin-like domain of thrombomodulin (THBD), which is known as THBD domain 1 (THBDD1) and which acts independently of protein C activation, neutralised an inflammatory response in a mouse model of sepsis. Here, therapeutic effects of gene therapy with adeno-associated virus (AAV)-carried THBDD1 (AAV-THBDD1 ) were tested in a mouse model of type 2 diabetic nephropathy.Electronic supplementary material The online version of this article

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Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation

Cited by 226 publications

References 80 publications

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

Monosodium urate crystals trigger Nrf2- and heme oxygenase-1-dependent inflammation in THP-1 cells

Thrombomodulin domain 1 ameliorates diabetic nephropathy in mice via anti-NF-κB/NLRP3 inflammasome-mediated inflammation, enhancement of NRF2 antioxidant activity and inhibition of apoptosis

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