Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells — up regulation of Nrf2 expression and down regulation of NF-κB and COX-2

Ramyaa, Periasamy; Krishnaswamy, Rajashree; Padma, Viswanadha Vijaya

doi:10.1016/j.bbagen.2013.10.024

Cited by 168 publications

(110 citation statements)

References 51 publications

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“…Furthermore, activation of Nrf2 by pre-incubation with the quercetin prevented OTAinduced cell death (Morales et al, 2006;Ramyaa, Krishnaswamy, & Padma, 2014), which can be a possible mechanism in our conditions. The effect of polyphenolic/flavonoid components, including quercetin, on epigenetic and genetic processes, mechanisms of DNA damage repair, genomic stability, down-regulation of NF-κB and COX-2 and inhibition of carcinogenesis is also confirmed (Benkovic et al, 2008;Morales et al, 2006;Moskaug et al, 2004;Oršolić, 2009Oršolić, , 2010Oršolić et al, 2007Oršolić et al, , 2010Oršolić et al, , 2011Oršolić & Car, 2014;Piljac-Žegarac et al, 2009;Ramyaa et al, 2014;Sirovina et al, 2013).…”

Section: Food and Agricultural Immunologymentioning

confidence: 95%

Honey and quercetin reduce ochratoxin A-induced DNA damage in the liver and the kidney through the modulation of intestinal microflora

Oršolić

Jembrek

Terzić

2017

Food and Agricultural Immunology

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This study was conducted to evaluate the interactions between the gut microbiota, ochratoxin A and functional food such as honey and quercetin, and the consequences of these interactions on ochratoxin-induced DNA damage in blood, liver and kidney cells. Honey (2 g kg −1 ) or Quercetin (50 mg kg −1 ) was applied to mice by intragastric application every day for 15 days, immediately before ochratoxin treatment (100 µg kg −1 ). We investigated colonic probiotic bacteria count, β-glucuronidase activity, the alkaline comet assay in blood, liver and kidney, the number of cells in the peritoneal cavity, macrophage spreading index and hematological and biochemical parameters. Honey and QU may reduce ochratoxin-induced DNA damage in the liver and kidney, β-glucuronidase activity and inflammation, partly through increasing the colon Bifidobacteria and Lactobacilli counts. The obtained results suggest that honey and QU counteracted the OTA-induced toxicity due to their bifidogenic activity and antigenotoxic activity. ARTICLE HISTORY

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Section: Food and Agricultural Immunologymentioning

confidence: 95%

Honey and quercetin reduce ochratoxin A-induced DNA damage in the liver and the kidney through the modulation of intestinal microflora

Oršolić

Jembrek

Terzić

2017

Food and Agricultural Immunology

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“…It reduces H 2 O 2 -induced oxidative stress and ROS generation in human hepatocellular carcinoma (HepG2) cells (17) and ameliorates hepatic inflammation and fibrosis in mice with NASH (28). Quercetin also induces Nrf2 nuclear translocation and expression in ochratoxin A-exposed HepG2 cells (42) and rats with high fructose-, sucrose-, and fat diet-induced NAFLD (38). In our previous studies, allopurinol and quercetin reduced serum and renal TG and total cholesterol (TC) levels and suppressed renal NLRP3 inflammasome activation in fructose-fed rats (13,14).…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

Zhang

Chen

et al. 2015

Antioxidants & Redox Signaling

207

144

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Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and proinflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructoseexposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant-based interventions can inhibit the ROS-TXNIP pathway. Antioxid. Redox Signal. 22, 848-870.

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“…In this regard, there remains the possibility that induction of Nrf-2 target genes contributes to both quercetin and monochloropivaloylquercetin's efficacy to inhibit COX-2 expression. Ramyaa et al 50 have already reported the modulatory effect of quercetin on oxidative stress by upregulating Nrf-2 expression and downregulating NFkB and COX-2 expression. The anti-inflammatory properties of quercetin accompanied by an increase in HO-1 protein levels associated with elevated nuclear translocation of Nrf-2 were previously exhibited by Boesch-Saadatmandi et al 51 in murine RAW 264.7 macrophages.…”

Section: Discussionmentioning

confidence: 99%

Effect of the Lipid Peroxidation Product 4-Hydroxynonenal on Neuroinflammation in Microglial Cells: Protective Role of Quercetin and Monochloropivaloylquercetin

Cumaoğlu

Agkaya

Ozkul

2019

tjps

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Objectives:The lipid peroxidation-derived aldehyde 4-hydroxynonenal (HNE) has been implicated in a number of oxidative stress-induced inflammatory pathologies such as neurodegenerative diseases and aging. In this regard, we investigated the effects of HNE on neuroinflammatory responses by measuring cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) induction with cytokine production. In addition, we measured nuclear factor erythroid 2-related factor 2 (Nrf-2)/Kelch-like ECH-associated protein 1 (Keap1) signaling proteins, and antioxidant enzymes heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1), and compared the results with quercetin and monochloropivaloylquercetin (MPQ) pretreated microglial cells. Materials and Methods: Cytotoxicity was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and production of cytokines was determined by cytokine array. Furthermore, intracellular Nfr2/Keap1 signaling proteins, HO-1, NQO1, and COX-2 expression were analyzed by western blot in 2.5 μM HNE treated BV-2 cells. Results: Inducible nitric oxide synthase (iNOS) and COX-2 mRNA levels were measured with reverse transcription-quantitative polymerase chain reaction. HNE induced both COX-2 mRNA and protein levels, iNOS mRNA expression, and cytokine production. In addition, HNE markedly increased Keap1 levels and decreased cytoplasmic Nrf-2 expression with antioxidant enzyme HO-1 levels. Quercetin and monochloropivaloylquercetin treatment alleviated neuroinflammatory responses in microglial cells, by decreasing COX-2 mRNA expression. Monochloropivaloylquercetin decreased cytoplasmic Keap1 levels and increased nuclear translocation of Nrf-2 resulted in induction of HO-1 and NQO1 expression. Conclusion: These results suggest that HNE could be a link between oxidative stress and inflammation in BV-2 microglia cells. In particular, monochloropivaloylquercetin alleviated inflammation, probably by decreasing the expression of proinflammatory genes and strengthening the antioxidant defense system. Key words: 4-Hydroxynonenal, microglia, quercetin, inflammation, cyclooxygenase-2, hemeoxygenase-1 ÖZ Amaç: Lipit peroksidasyonu ürünü aldehit, 4-hidroinonenal (HNE), nörodejeneratif hastalıklar ve yaşlanma gibi oksidatif strese bağlı inflamatuvar patolojilerle ilişkilendirilmiştir. Bu bağlamda, HNE'nin nöroinflamatuvar cevap üzerine etkisini siklooksijenaz-2 (COX-2), indüklenebilir nitrik oksit sentaz (iNOS) ifadelenmeleri ve sitokin üretimi üzerinden incelenmiştir. Bunlara ek olarak, nükleer faktör eritroid 2-ilişkili faktör 2 (Nrf2)/ Kelch-benzeri ECH-ilişkili protein 1 (Keap1) sinyal proteinleri, antioksidan enzimler hemoksijenaz-1 (HO-1) ve nikotinamid adenin dinükleotit fosfat dehidrojenaz, kinon 1 (NQO1) ifadelenme düzeyleri ölçüldü ve sonuçlar kersetin ve monokloropivaloilkersetin uygulanan hücrelerle karşılaştırılmıştır. Gereç ve Yöntemler: Sitotoksisite MTT (3-(4,5-dimetiltiyazol-2-yl)-2,5-difeniltetrazolyum bromit) indirgenme y...

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Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells — up regulation of Nrf2 expression and down regulation of NF-κB and COX-2

Cited by 168 publications

References 51 publications

Honey and quercetin reduce ochratoxin A-induced DNA damage in the liver and the kidney through the modulation of intestinal microflora

Honey and quercetin reduce ochratoxin A-induced DNA damage in the liver and the kidney through the modulation of intestinal microflora

Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

Effect of the Lipid Peroxidation Product 4-Hydroxynonenal on Neuroinflammation in Microglial Cells: Protective Role of Quercetin and Monochloropivaloylquercetin

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