The effects of quercetin on oxidative stress and fibrosis markers in chronic kidney disease rat model

Background: Oxidative stress may play a role in the pathogenesis of (CKD), Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor involved in cell defense mechanism against oxidative stress. In this study, we examined the effect of quercetin, a polyphenplic antioxidant anti fibrosis compund in fruits and vegetables, on the 5/6 nephrectomy-induced CKD progression model rats through modulation of Nrf2 expression.Methods: Male Sprague-Dawley rats were randomly divided into normal control group (C), untreated 5/6 nephrectomy (Nx), quercetin-treated 5/6 nephrectomy (100 mg/kgBW/day orally) (NxQ), and captopril-treated 5/6 nephrectomy (10 mg/kgBW/day orally) (NxK) for 8 weeks. At the end of study, all animals were sacrified. Urine, blood, and kidney tissues were taken for examination of proteinuria, plasma creatinine, urea, malondialdehyde (MDA), glutathione peroxidase (GPx) activity, Nrf2, Keap1, heme oxygenase-1 (HO-1) expressions, and renal fibrosis.Results: Quercetin administration did not affect the level of protein in urine, plasma creatinine, and urea. However, it tended to reduce the level of MDA, increase GPx activity, Nrf2, Keap1, and HO-1 expression as well as the degree of fibrosis.Conclusion: In 5/6 nephrectomized rats, quercetin tended to ameliorate the level of MDA, GPx activity, Nrf2, Keap1, and HO-1 expression. In addition, quercetin tended to decrease the degree of fibrosis in the remnant kidney.

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Sodium tanshinone IIA sulfate protects myocardium against paraquat-induced toxicity through activating the Nrf2 signaling pathway in rats

Human & Experimental Toxicology ◽

10.1177/0960327118792051 ◽

2018 ◽

Vol 38 (2) ◽

pp. 247-254 ◽

Cited By ~ 1

Author(s):

WX Zhang ◽

XY Xiao ◽

CG Peng ◽

WL Chen ◽

S Xie ◽

...

Keyword(s):

Tanshinone Iia ◽

Control Group ◽

Heme Oxygenase 1 ◽

Intragastric Administration ◽

Related Factor ◽

Dependent Manner ◽

Myocardial Cells ◽

Sprague Dawley ◽

Nrf2 Pathway ◽

Nrf2 Signaling Pathway

Objective: To investigate the therapeutic effect and mechanism of sodium tanshinone IIA sulfate (STS) on paraquat (PQ)-induced myocardial injuries in a rat model. Methods: Healthy adult Sprague Dawley rats were randomly divided into normal control, PQ, and PQ + STS groups. PQ group was given a single intragastric administration of PQ (80 mg/kg). PQ + STS group was intraperitoneally injected with STS (1 ml/kg) at 30 min following PQ exposure. Rats in control and PQ groups were injected with equal amount of saline. After 12, 24, 48, and 72 h, rats were killed, and the apoptosis of myocardial cells was detected. Myocardial expression of Bax and Bcl-2 was measured. The activity of the nuclear erythroid 2-related factor 2 (Nrf2) pathway was assessed by Western blot. Results: The apoptotic cells in PQ group were significantly increased in a time-dependent manner compared with the control group ( p < 0.01). The rats in PQ group exhibited significantly lower Bcl-2 expression, but notably higher Bax expression at 12, 24, 48, and 72 h after PQ exposure ( p < 0.05 or 0.01). STS intervention markedly reduced the proportion of apoptotic myocardial cells, increased Bcl-2 expression, and decreased Bax expression at 24, 48, and 72 h after treatment ( p < 0.05 or 0.01). The expression of phosphorylated Nrf2 and heme oxygenase 1 in PQ + STS group was significantly increased compared with PQ and control groups ( p < 0.05 or 0.01). Conclusion: STS effectively inhibits PQ-induced myocardial cell apoptosis in rats via modulating the Nrf2 pathway, suggesting its potential as a promising therapeutic agent for PQ-induced myocardium damage.

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Protective Effect of Decursin Extracted fromAngelica gigasin Male Infertility via Nrf2/HO-1 Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/5901098 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Woong Jin Bae ◽

U. Syn Ha ◽

Jin Bong Choi ◽

Kang Sup Kim ◽

Su Jin Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Semen Quality ◽

Antioxidant Activities ◽

Control Group ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Dependent Manner ◽

Testicular Weight ◽

Unilateral Cryptorchidism

Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted fromAngelica gigasNakai on antioxidant activityin vitroand in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg ofA. gigasextract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment withA. gigasextract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted fromA. gigasis a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.

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Sodium arsenite induces spatial learning and memory impairment associated with oxidative stress and activates the Nrf2/PPARγ pathway against oxidative injury in mice hippocampus

Toxicology Research ◽

10.1093/toxres/tfab007 ◽

2021 ◽

Author(s):

Liang Xiong ◽

Jinyu Huang ◽

Ying Gao ◽

Yanfang Gao ◽

Chunmei Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Sodium Arsenite ◽

Defense Mechanism ◽

Antioxidant Defenses ◽

Spatial Learning And Memory ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Antioxidant Genes ◽

Pparγ Expression

Abstract Arsenic (As) is a ubiquitous environmental and industrial toxin with known correlates of oxidative stress and cognitive deficits in the brain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that represents a central cellular antioxidant defense mechanism and transcribes many antioxidant genes. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a well-known nuclear receptor to regulate lipid metabolism in many tissues, and it has been also associated with the control of oxidative stress, neuronal death, neurogenesis and differentiation. The role of Nrf2 and PPARγ in As-induced neurotoxicity is still debated. The present study was designed to investigate the neurobehavioral toxic effect of sub-chronic and middle-dose sodium arsenite exposure in mice hippocampus, as well as the response of Nrf2/PPARγ expression and influence on protein expression levels of their downstream antioxidant genes. Our results showed that mice treated with intraperitoneal injection of sodium arsenite (50 mg/kg body wt.) twice a week for 7 weeks resulted in increased generation of reactive oxygen species and impairment of spatial cognitive function. The present study also found a positive association between Nrf2/PPARγ expression in hippocampus of mice, and activation of antioxidant defenses by the evidently upregulated expression of their downstream genes, including superoxide dismutase, heme oxygenase-1 and glutathione peroxidase-3. Therefore, our findings were helpful for further understanding the role of Nrf2/PPARγ feedback loop in As-induced neurobehavioral toxicity.

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Astaxanthin Suppresses Cigarette Smoke-Induced Emphysema through Nrf2 Activation in Mice

Marine Drugs ◽

10.3390/md17120673 ◽

2019 ◽

Vol 17 (12) ◽

pp. 673 ◽

Cited By ~ 8

Author(s):

Hiroaki Kubo ◽

Kazuhisa Asai ◽

Kazuya Kojima ◽

Arata Sugitani ◽

Yohkoh Kyomoto ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Defense Mechanism ◽

Inflammatory Cells ◽

Lavage Fluid ◽

Chronic Obstructive ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Obstructive Pulmonary Disease ◽

Suppression Effect

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key cellular defense mechanism against oxidative stress. Recent studies have shown that astaxanthin protects against oxidative stress via Nrf2. In this study, we investigated the emphysema suppression effect of astaxanthin via Nrf2 in mice. Mice were divided into four groups: control, smoking, astaxanthin, and astaxanthin + smoking. The mice in the smoking and astaxanthin + smoking groups were exposed to cigarette smoke for 12 weeks, and the mice in the astaxanthin and astaxanthin + smoking groups were fed a diet containing astaxanthin. Significantly increased expression levels of Nrf2 and its target gene, heme oxygenase-1 (HO-1), were found in the lung homogenates of astaxanthin-fed mice. The number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) was significantly decreased, and emphysema was significantly suppressed. In conclusion, astaxanthin protects against oxidative stress via Nrf2 and ameliorates cigarette smoke-induced emphysema. Therapy with astaxanthin directed toward activating the Nrf2 pathway has the potential to be a novel preventive and therapeutic strategy for COPD.

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Roles of oxidative stress, apoptosis, and heme oxygenase-1 in ethylbenzene-induced renal toxicity in NRK-52E cells

Toxicology and Industrial Health ◽

10.1177/0748233715602834 ◽

2016 ◽

Vol 32 (12) ◽

pp. 1952-1960

Author(s):

Ming Zhang ◽

Yanrang Wang ◽

Xiaojun Wang ◽

Jing Liu ◽

Jingshu Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Heme Oxygenase ◽

Messenger Rna ◽

Renal Toxicity ◽

Control Group ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Dependent Manner ◽

Dose Dependent

Ethylbenzene is an important industrial chemical, but its potential toxicity is a recent concern. Our previous study investigated the renal toxicity of ethylbenzene in vivo. Rat renal epithelial cells (NRK-52E cells) were incubated with 0, 30, 60, and 90 µmol/L of ethylbenzene for 24 h in vitro to investigate ethylbenzene-induced oxidative stress, apoptosis, and the expression of heme oxygenase 1 (HO-1) and nuclear factor (erythroid 2)-related factor 2 (Nrf2). The cell survival rate in the ethylbenzene-treated groups was significantly lower than the control group. Ethylbenzene significantly increased intracellular reactive oxygen species and apoptosis. Malondialdehyde levels were significantly elevated compared with the control group, while glutathione levels and glutathione peroxidase activities were decreased in ethylbenzene-treated groups. The activities of catalase and superoxide dismutase were also markedly reduced. A significant dose-dependent increase in HO-1 and Nrf2 messenger RNA expression levels was observed in ethylbenzene-treated groups compared with the control group. Similarly, ethylbenzene treatment enhanced protein expression of HO-1 and Nrf2 in a dose-dependent manner. Our results indicated that ethylbenzene induced oxidative stress, apoptosis, and upregulation of HO-1 and Nrf2 in NRK-52E cells, which contributes to ethylbenzene-induced renal toxicity.

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PIAS3 suppresses damage in an Alzheimer’s disease cell model by inducing the STAT3-associated STAT3/Nestin/Nrf2/HO-1 pathway

Molecular Medicine ◽

10.1186/s10020-021-00410-3 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Chen Li ◽

Ruili Wang ◽

Youyou Zhang ◽

Chunting Hu ◽

Qiaoya Ma

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cell Model ◽

Control Group ◽

Heme Oxygenase 1 ◽

Related Factor ◽

A Cell ◽

The Central Nervous System ◽

And Oxidative Stress

Abstract Background Alzheimer’s disease (AD), the most common form of dementia, is caused by the degeneration of the central nervous system (CNS). A previous study reported that signal transducer and activator of transcription 3 (STAT3) is activated during AD development; nonetheless, the related mechanism remains unknown. Thus, this study used a cell model to explore whether and how the protein inhibitor of activated STAT3 (PIAS3) is involved in AD development. Methods Cerebrospinal fluid (CSF) specimens of 30 patients with AD and 10 normal participants were included in this study. SH-SY5Y cells were used to constructed AD model. Relevant indices were then detected and analyzed. Results The results showed that compared with the control group, PIAS3 expression was substantially decreased in patients with AD and amyloid beta (Aβ)-treated SH-SY5Y cells. PIAS3 overexpression was able to reverse the detrimental effects of Aβ treatment on cell survival and growth. Further, it could also ameliorate apoptosis and oxidative stress in Aβ-treated SH-SY5Y cells. Additionally, PIAS3 was shown to reduce the activated form of STAT3 and increase the activity of the downstream Nestin/nuclear factor erythroid 2-related factor/heme oxygenase-1 pathway. Conclusions STAT3 reactivation by colivelin treatment negated the influence of PIAS3 on the survival, growth, apoptosis, and oxidative stress of Aβ-treated SH-SY5Y cells.

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Effect of Noni on memory impairment induced by hydrocortisone in mice

10.21203/rs.3.rs-763583/v1 ◽

2021 ◽

Author(s):

RUI ZHANG ◽

JINLIAN LIU ◽

XINJUAN HOU ◽

FAN ZHAO ◽

CHANDI WANG ◽

...

Keyword(s):

Oxidative Stress ◽

Memory Impairment ◽

Control Group ◽

Heme Oxygenase 1 ◽

High Dose ◽

Related Factor ◽

Model Group ◽

Protection Mechanism ◽

Protein Expressions ◽

Biochemical Analyses

Abstract Background Oxidative stress and memory impairment have been implicated, a common functional brain disease. Nuclear factor E2-related factor 2 (Nrf2) is highly induced in oxidative stress, indicating that Nrf2 is an emerging target of memory therapy. This study aimed to investigate the effect of Noni on brain memory impairment induced by hydrocortisone and its protection mechanism in mice. Methods Male Kuming mice were (n = 8/group) given hydrocortisone by gastric gavage for 14 consecutive days to establish the memory impairment model except for those in the control group. At the same day, the corresponding drugs were given by gastric gavage. The changes in ethology were examined. Brains were extracted and subjected to western blot analysis and biochemical analyses to assess the activities of oxidative stress. Results The middle and high-dose Noni groups ameliorated the ethology and the high-dose Noni group increased cerebral protein expressions of Nrf2, kelch-like ECH-associated protein 1 (KEAP1) and heme oxygenase-1 (HO-1), as compared to the model group. The arrangement of CA3 vertebral cells in hippocampus of mice was slightly compact and hyperchromatic and pyknosis were alleviated. Furthermore, the biochemical analyses showed the activities of related enzymes of oxidative stress in high-dose Noni group were increased. Conclusions Noni might be a powerful antioxidant that can protect nerve cell and may possess as a potential benefit for the treatment of memory impairment.

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Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/7286958 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Liren Zhong ◽

Wei Ding ◽

Qingyu Zeng ◽

Binglin He ◽

Haibo Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Erectile Dysfunction ◽

Antioxidant Capacity ◽

Erectile Function ◽

Tanshinone Iia ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Sprague Dawley ◽

Sodium Tanshinone Iia Sulfonate

Hyperlipidemia is considered one of the most important risk factors for erectile dysfunction (ED). To determine the effect of sodium tanshinone IIA sulfonate (STS) as an antioxidant agent on ED in high-fat diet- (HFD-) induced hyperlipidemia in rats and to investigate if STS administration could improve erectile function via hydrogen sulfide (H2S) production by inhibition of oxidative stress. Hyperlipidemia was induced in Sprague-Dawley rats by feeding HFD for 16 weeks. The rats were randomly divided into 3 groups: control, HFD, and HFD treated with STS (10 mg/kg/day for 12 weeks, intraperitoneal injection). Erectile function including intracavernosal pressure (ICP), H2S production, and antioxidant capacity was assessed. In addition, cavernosal smooth muscle cells (CSMC) isolated from SD rats were pretreated with STS in vitro and exposed to H2O2. Expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), activity of antioxidant enzymes, and H2S-generating enzymes within CSMC were examined. ICP was significantly decreased in HFD rats compared with control. In addition, decreased H2S production and expression of cystathionine ɣ-lyase (CSE) and cystathionine β-synthase (CBS) associated with increased oxidative stress were observed in the penile tissue of HFD rats. However, all these changes were reversed by 16 weeks after STS administration. STS also increased antioxidant defense as evidenced by increased expression of Nrf2/HO-1 in the penile tissue of HFD rats. In CSMC, pretreatment with STS attenuated the decreased expression of CSE and CBS and H2S production by H2O2. STS exerted similar protective antioxidative effect as shown in the in vivo hyperlipidemia model. The present study demonstrated the redox effect of STS treatment on ED via increased H2S production in HFD-induced hyperlipidemia rat model by increased antioxidant capacity via activation of the Nrf2/HO-1 pathway, which provides STS potential clinical application in the treatment of hyperlipidemia-related ED.

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Activation of Nrf2/HO-1 Pathway and Human Atherosclerotic Plaque Vulnerability:an In Vitro and In Vivo Study

Cells ◽

10.3390/cells8040356 ◽

2019 ◽

Vol 8 (4) ◽

pp. 356 ◽

Cited By ~ 6

Author(s):

Fiorelli ◽

Porro ◽

Cosentino ◽

Di Minno ◽

Manega ◽

...

Keyword(s):

Oxidative Stress ◽

Healthy Subjects ◽

Defense Mechanism ◽

Thrombus Formation ◽

Coronary Plaque ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Oxidative Stress Status

Reactive oxygen species (ROS) induce nuclear factor erythroid 2–related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque.

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Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt and CaMKKβ/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation

Antioxidants ◽

10.3390/antiox10060897 ◽

2021 ◽

Vol 10 (6) ◽

pp. 897

Author(s):

Wen-Ping Jiang ◽

Jeng-Shyan Deng ◽

Shyh-Shyun Huang ◽

Sheng-Hua Wu ◽

Chin-Chu Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Kinase ◽

Liver Failure ◽

Acute Liver Failure ◽

Mitogen Activated Protein Kinase ◽

Heme Oxygenase 1 ◽

Molecular Evidence ◽

Related Factor ◽

Serum Aminotransferase ◽

Compound C

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

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