Protective Potential of Adiponectin and Quercetin on Alleviating Bisphenol-A-Induced Toxicity in Muscle Cells Through the KEAP1/NRF2 Pathway

Abstract Background: Bisphenol A (BPA) is a toxic environmental estrogenic compound which exerts its detrimental effects by increasing oxidative stress and decreasing levels of antioxidants. This study aimed to evaluate beneficial effect of adiponectin and quercetin in reducing BPA-induced oxidative stress by assessing the Prooxidant-antioxidant balance (PAB) assay, catalase activity and KEAP1/NRF2 expression in muscle cells.Methods and Results: L6 rat muscle cells were exposed to BPA (50 an100 μM) with and without treatment with different concentrations of adiponectin (10 and 100 ng/ml) and quercetin (10 and 25 ng/ml) for 24 and 48 hours. Cell viability was assessed using MTT assay, and the PAB was evaluated with the ELISA at 540 nm. Catalase level was also evaluated in all groups. Furtheremore, the expression of KEAP1/Nrf2 genes was assessed using qRT-PCR. The results showed a significant reduction in L6 cells survival after being treated with 100 μM BPA. Adiponectin and quercetin treatment also increased cell survival compared to BPA-treated cells. It was also found that PAB increased with BPA exposure, and quercetin treatment significantly reduced it compared to BPA treatment. The catalase activity was reduced in BPA-treated cells, which was significantly increased by treatment with adiponectin and quercetin. A significant decrease in Nrf2 gene expression was observed in BPA-treated cells compared to the control group. It was further found that cell treatment with quercetin and adiponectin significantly increased the expression of Nrf2 gene compared to the control group.Conclusions: Taking together, our results implied that adiponectin and quercetin could modulate BPA-induced oxidative stress in muscle cells through KEAP1/Nrf2 pathway. Accordingly, it can be concluded that adiponectin in low dose and quercetin, may have significant impact in reducing toxicity due to BPA.

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Protective effect of GSK-3β/Nrf2 mediated by dimethyl fumarate in middle cerebral artery embolization reperfusion rat model

Current Neurovascular Research ◽

10.2174/1567202618666211109105024 ◽

2021 ◽

Vol 18 ◽

Author(s):

Yuan Li ◽

Lan Chu ◽

Chunfeng Liu ◽

Zongyi Zha ◽

Yuanlu Shu

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Sham Group ◽

Infarct Volume ◽

Dimethyl Fumarate ◽

Control Group ◽

Related Factor ◽

Nissl Staining ◽

Gsk 3Β ◽

Nrf2 Expression

Aim: This study investigated the protective effect of dimethyl fumarate (DMF) in rats by mediating GSK3-β/Nrf2 using the middle cerebral artery embolization reperfusion (MCAO/R) rat model. Background: After an acute ischemic stroke (AIS), oxidative stress occurs. Dimethyl fumarate (DMF), a nuclear factor-E2-related factor 2 (Nrf2) activator, approved by the US Food and Drug Administration (FDA), was observed to regulate the Nrf2 pathway by acting as an anti-oxidative stress agent; however, whether this agent is involved in inhibiting GSK-3β remains to be established. Methods: DMF model was used to explore the effects of GSK-3β on Nrf2 expression level, Nrf2-ARE binding activity and Nrf2/ARE downstream expression level of anti-oxidant stress protein in Cerebral ischemia-reperfusion injury (CIRI). 60 rats were randomly divided into Sham group, MCAO/R group, solvent control group (DMSO group) and DMF treatment group, with 15 rats in each group. The MCAO/R, DMSO and DMF groups were considered in the MCAO/R model using the modified thread embolization method. In contrast, the Sham group was only anaesthetized and disinfected, and tissue muscle was dissected without inserting suture emboli. DMF group was gavaged with 45mg/kg per day of DMF, DMSO control group was gavaged with DMSO of equal volume, while MCAO/R group was only modeled without any intragastric treatment. The rats were treated seven days after the operation, and a neurological function Longa score was estimated. The rats were sacrificed seven days later, and the infarct volume was assessed by TTC staining. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in rat brain tissue. Nissl staining was used to observe the expression of neurons in the infarcted cortex. Western blotting (WB) was used to observe the protein expression levels of glycogen synthase kinase 3β(GSK-3β), nuclear factor E2-related factor 2 (Nrf2), downstream heme oxygenase 1 (HO1) and NADPH quinone oxidoreductase 1 (NQO1) in four groups. The expression levels of GSK-3β and Nrf2 in the four groups were observed by immunohistochemistry and immunofluorescence. Results: (1) The Longa score of the MCAO/R, DMSO and DMF groups was found to be higher compared to the Sham group, indicating successful operation. The Longa score of the DMF group was lower than that of the other three groups 4-7 days after surgery (P<0.05). (2) HE and Nissl staining showed that the DMF group had lower neuron necrosis and higher gliosis compared to the control groups. (3) TTC staining results showed that the infarct volume of the DMF group was significantly smaller than the MCAO/R and DMSO groups. (4) Protein results showed that the GSK-3β expression in the DMF group was lower than that in all groups, while the expression of Nrf2, HO1 and NQO1 was higher compared to other groups. Conclusion: DMF can reduce neurological deficits and infarct size in the MCAO/R model. The protective effect may be related to decreased GSK-3β expression and increased Nrf2 expression, which may play a role in anti-oxidative stress.

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DHEA Alleviates Oxidative Stress of Muscle Cells via Activation of Nrf2 Pathway

Applied Biochemistry and Biotechnology ◽

10.1007/s12010-015-1500-y ◽

2015 ◽

Vol 176 (1) ◽

pp. 22-32 ◽

Cited By ~ 9

Author(s):

Songhee Jeon ◽

Jinyoung Hur ◽

Jongpil Kim

Keyword(s):

Oxidative Stress ◽

Muscle Cells ◽

Nrf2 Pathway

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Proanthocyanidins-Mediated Nrf2 Activation Ameliorates Glucocorticoid-Induced Oxidative Stress and Mitochondrial Dysfunction in Osteoblasts

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9102012 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Liang Chen ◽

Sun-Li Hu ◽

Jun Xie ◽

De-Yi Yan ◽

She-Ji Weng ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Low Dose ◽

Distal Femur ◽

Therapeutic Potential ◽

Protective Effects ◽

Nrf2 Pathway ◽

Pathway Activation ◽

Nrf2 Activation ◽

Osteoblast Apoptosis

The widespread use of therapeutic glucocorticoids has increased the frequency of glucocorticoid-induced osteoporosis (GIOP). One of the potential pathological processes of GIOP is an increased level of oxidative stress and mitochondrial dysfunction, which eventually leads to osteoblast apoptosis. Proanthocyanidins (PAC) are plant-derived antioxidants that have therapeutic potential against GIOP. In our study, a low dose of PAC was nontoxic to healthy osteoblasts and restored osteogenic function in dexamethasone- (Dex-) treated osteoblasts by suppressing oxidative stress, mitochondrial dysfunction, and apoptosis. Mechanistically, PAC neutralized Dex-induced damage in the osteoblasts by activating the Nrf2 pathway, since silencing Nrf2 partly eliminated the protective effects of PAC. Furthermore, PAC injection restored bone mass and promoted the expression of Nrf2 in the distal femur of Dex-treated osteoporotic rats. In summary, PAC protect osteoblasts against Dex-induced oxidative stress and mitochondrial dysfunction via the Nrf2 pathway activation and may be a promising drug for treating GIOP.

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Dietary quercetin ameliorates TPT-induced hepatic oxidative damage and apoptosis in zebrafish

10.21203/rs.3.rs-339016/v1 ◽

2021 ◽

Author(s):

Chunnuan Zhang ◽

Yuheng Wang ◽

Hongtao Ren ◽

Junhui Wang ◽

Dongxue Jiang ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Basal Diet ◽

Control Group ◽

Antioxidant Enzyme Activities ◽

Mrna Levels ◽

Gene Expressions ◽

Apoptotic Gene ◽

Tnf Α ◽

Quercetin Treatment

Abstract The objective of this study was to determine the effects of quercetin on oxidative stress and apoptosis induced by TPT in zebrafish. 240 fish were divided into 4 groups with three repeats. D1: fish fed with the basal diet as the control group. D2: fish fed with basal diet and exposed in 10 ng/L TPT. D3: fish fed diets containing 100 mg/Kg quercetin and exposed in 10ng/L TPT. D4: fish fed diets containing 100 mg/Kg quercetin. The results showed that quercetin could ameliorate oxidative stress, which decreased MDA, NO levels and improved antioxidant enzyme activities. The key apoptotic gene expressions, including caspase3, Bax and caspase9 mRNA expression were significantly induced by TPT exposure as compared with the control group, while notably decreased the Bcl-2 gene. However, dietary quercetin prevented a significant increase in Bax, caspase3 and caspase9 mRNA levels induced by TPT exposure, but increased Bcl-2 mRNA levels. The results of our study also demonstrated that 10 ng/L TPT significantly up-regulated TNF-α, IL-1β, IL-8, and NF-kB p65 gene expression and down-regulated IL-10 and IkB expression compared to the control group. However, TPT-induced inflammation was significantly mitigated in the quercetin treatment group. In conclusion, our findings suggested that quercetin might alleviate hepatic oxidative damage and apoptosis induced by TPT.

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THE COMPARATIVE ROLE OF ASCORBATE AND CHELATORS IN REVERSING OXIDATIVE STRESS, HEPATIC AND RENAL DYSFUNCTION IN SUB-ACUTE LEAD POISONING

Journal of Natural Sciences Engineering and Technology ◽

10.51406/jnset.v14i1.1496 ◽

2016 ◽

Vol 14 (1) ◽

pp. 89-102

Author(s):

B. O. ONUNKWOR ◽

R. N. UGBAJA ◽

D. A. OMONIYI ◽

A. O. DOSUMU

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Lead Poisoning ◽

Catalase Activity ◽

Lead Level ◽

Blood Lead ◽

Therapeutic Interventions ◽

Control Group ◽

Male Wistar Rats ◽

Species Production

Lead has been implicated in the induction of reactive species production, leading to organ dysfunctions. The ameliorative roles of ascorbate and chelators in acute lead poisoning were comparatively studied in thirty-five male Wistar rats (150-200g), segregated into 5 groups (n=7/Group): group 1(administered normal saline),ª¤? groups 2-5 were orally exposed to 75mg/kg body weight lead acetate (PbAc) daily for 14 days. Pre-therapy blood samples were collected to ascertain blood lead level (BLL) and catalase activity 24hours after the last PbAc exposure. Groups 3, 4, and 5 were then treated with 30mg/kg body weight D-penicillamine; 30mg/kg body weight succimer; and 500mg/kg body weight ascorbate respectively for 10 days, followed by the assay for indices of oxidative stress, hepatic and renal dysfunctions.ª¤? Results obtained showed significantly elevated BLL in the four groups exposed to PbAc. which were significantly reversed about 2 folds in groups 3-5 after therapeutic interventions. Pre-therapy blood catalase activity of the PbAc treated groups was significantly (p<0.05) reduced by 39% when compared with the control group, however ascorbate significantly (p<0.05) increased catalase activity by 2 folds above the control; decreased plasma activities of alanine transaminase and aspartate transaminase, blood urea nitrogen and creatinine among the groups administered therapeutics. These findings indicate that ascorbate is more effectiveª¤?

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Induction Effect of Bisphenol A on Gene Expression Involving Hepatic Oxidative Stress in Rat

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/6298515 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 16

Author(s):

Sohrab Kazemi ◽

Seydeh Narges Mousavi ◽

Fahimeh Aghapour ◽

Boshra Rezaee ◽

Farzin Sadeghi ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Bisphenol A ◽

Corn Oil ◽

Rna Extraction ◽

Control Group ◽

Induction Effect ◽

Hepatic Oxidative Stress ◽

Body Weights ◽

Male Wistar Rats

Background and Objective.Bisphenol A (BPA) is an abundantly used xenoestrogenic chemical which may cause various disorders in body. In the present study, we sought to investigate the effects of various doses of BPA on hepatic oxidative stress-related gene expression in rats.Methods.Male Wistar rats weighing 150–200 g were used in this study. Three doses of the BPA (5, 25, and 125 μg/kg) in corn oil were administered as gavage during 35 consecutive days. After the experiment, the rats were expired and the livers were removed and stored at −80°C freezer for RNA extraction.Findings.The Real Time PCR showed increased expression of HO-1 in the rats receiving BPA doses compared to the control group. This effect was dose-dependent and higher at doses of 25 and 125 μg/kg than 5 μg/kg of body weight (p<0.05). It was also demonstrated that various doses BPA can increase GADD45B gene expression compared to control group. That expression was significantly dominant in the lowest dose (5 μg/kg) of the BPA (p<0.05). The final body weights (168.0±10.0 gr) in the treatment group [BPA (125 μg/kg)] showed a significant decrease compared to control group (191.60±6.50 gr).Conclusion.These findings demonstrate that BPA generated ROS and increased the antioxidant gene expression that causes hepatotoxicity.

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Oxidative Stress Reduction by Midazolam Premedication during Oocyte Retrieval Procedure: Pilot Study

Journal of Clinical Medicine ◽

10.3390/jcm10040855 ◽

2021 ◽

Vol 10 (4) ◽

pp. 855

Author(s):

Maja Pešić ◽

Katarina Kličan-Jaić ◽

Marinko Vučić ◽

Krunoslav Kuna ◽

Andro Košec ◽

...

Keyword(s):

Oxidative Stress ◽

Pilot Study ◽

In Vitro Fertilization ◽

Stress Reduction ◽

Catalase Activity ◽

Oocyte Retrieval ◽

Control Group ◽

Medical Problems ◽

Vitro Fertilization

Infertility is one of the major medical problems nowadays. Couples who opt for In Vitro Fertilization (IVF) face a great deal of stress which certainly affects the outcome of the procedure. Therefore, we aimed to reduce the stress during the oocyte retrieval procedure by applying midazolam. Total oxidant (TOC) and antioxidant (TAC) capacities of serum, as well as glutathione (GSH) content and catalase activity, were measured in both control and midazolam groups. Follicular fluid was also tested for oxidant capacity and IL1β. Results implied that the midazolam group increased TAC at the end of the procedure. At the same time, the control group decreased GSH at the beginning of the procedure, and both groups decreased catalase activity at the end of the procedure. The results imply that stress during the procedure affects oxidative and antioxidative parameters of the patients, but did not affect the frequency of the pregnancy at the end of this pilot study. Yet, the results imply that oxidative and antioxidative mechanisms during IVF should be investigated in detail as they could affect the outcome of IVF.

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Total Antioxidant Capacity, Catalase Activity and Salivary Oxidative Parameters in Patients with Temporomandibular Disorders

Frontiers in Dentistry ◽

10.18502/fid.v17i16.4179 ◽

2020 ◽

Author(s):

Neda Omidpanah ◽

Saba Ebrahimi ◽

Asad Vaisi Raygani ◽

Hadi Mozafari ◽

Mansour Rezaei

Keyword(s):

Oxidative Stress ◽

Antioxidant Capacity ◽

Temporomandibular Disorders ◽

Catalase Activity ◽

Total Antioxidant Capacity ◽

Control Group ◽

Healthy Controls ◽

Oxidative Stress Biomarkers ◽

Reducing Ability ◽

Total Antioxidant

Objectives: Temporomandibular disorders (TMD) are characterized by pain or discomfort in the temporomandibular joint, periauricular region, masticatory muscles, and neck on one or both sides. It may also be associated with joint sounds, restricted mandibular movements and mandibular deviation. Oxidative agents may have a deleterious role in the pathogenesis of joint diseases, and oxidative stress can lead to TMD. The aim of this study was to assess the oxidative stress biomarkers in the saliva of TMD patients and healthy controls. Materials and Methods: This case-control study was conducted on 30 patients with TMDs (5 males and 25 females) with a mean age of 30.7±13.2 years, and 30 healthy controls (5 males and 25 females) with a mean age of 29.16±11.2 years. Saliva samples were collected according to the standard protocol and the total antioxidant capacity of the saliva (non-enzymatic), catalase activity, and malondialdehyde (MDA) levels were measured using the ferric reducing ability of plasma, Aebi’s method, and high-performance liquid chromatography, respectively. Finally, The MDA levels were analyzed by the Mann-Whitney test. Other quantitative parameters were analyzed by independent t-test. Results: TMD patients had significantly higher salivary levels of MDA compared to the control group (P=0.001). But there were no significant differences in catalase (P=0.49) and total antioxidant capacity (P=0.22) of TMD patients and healthy controls. Conclusion: It seems that oxidative stress may be involved in the pathogenesis of TMDs.

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PO-205 Effect of AMPK agonist / inhibitor on Nrf2 expression in C2C12 cells

Exercise Biochemistry Review ◽

10.14428/ebr.v1i5.8983 ◽

2018 ◽

Vol 1 (5) ◽

Author(s):

Lin Luo ◽

Ying Zhang

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Stress Response ◽

Energy Metabolism ◽

The Body ◽

C2c12 Cells ◽

Control Group ◽

Compound C ◽

Antioxidant Stress ◽

Nrf2 Expression

Objective In the past few decades, the study of skeletal muscle oxidative stress has been concerned about the increase of free radicals induced by muscle contraction. In recent years, the activation of antioxidant stress signaling pathway has gradually become one of the hot topics in the field of sports medicine. Although current research has confirmed that long-term aerobic training can bring health benefits to the body, the molecular mechanism of its role is still not very clear.Traditionally, AMPK has been regarded as the energy receptor of cells. During exercise, the energy consumption of skeletal muscle doubled, ATP decreased, AMP increased, and the ratio of AMP/ATP increased, thus inducing the activation of AMPK and regulating cell energy metabolism. Recent studies have found that AMPK not only plays an important role in the regulation of energy metabolism, but also plays a role in the body's antioxidant stress response. However, the relationship between AMPK and oxidative stress has been studied only in a small number of cells in non skeletal muscle cells. The results of this few studies show that oxidative stress in AMPK can not depend on the increase of intracellular AMP/ATP ratio, and the independent activation of AMPK, thus reducing the level of intracellular ROS, but the molecular mechanism of its action is not clear. Nrf2 is an important nuclear transcription factor in the body and plays an important role in the body's antioxidant stress response. Whether AMPK can participate in the regulation of Nrf2 mediated antioxidant activity in skeletal muscle has not been reported.In this study, the mouse skeletal muscle C2C12 cells were used in vitro cell experiments. The AMPK pharmacologic activator AICAR and the pharmacological inhibitor Compound C were used to treat the cells respectively. The role of AMPK in the regulation of Nrf2 expression in C2C12 cells and its mechanism were observed. Methods Cell experiments were performed on C2C12 cells of skeletal muscle of mice, and AMPK activator AICAR and AMPK inhibitor Compound C were used to intervene. The fluorescence intensity of C2C12 cells in each group was qualitatively detected by fluorescence inverted microscope, and the ROS level of C2C12 cells in each group was detected by fluorescence colorimetry. Results the ROS level of each group was significantly higher than that of the control group. RT-PCR assay was used to detect the antioxidant enzyme mRNA level of C2C12 cells in each group. Western Blot assay was used to detect the expression of AMPK alpha, pAMPK alpha, Nrf2, pNrf2 and antioxidant enzyme protein in C2C12 cells of each group. Results (1) compared with the control group, the pAMPK alpha /AMPK alpha ratio of C2C12 cells in the agonist group increased significantly, the expression of pNrf2 protein in the cells increased significantly, and the expression of NQO1mRNA, HO-1mRNA and GSR mRNA increased significantly, and the cells SOD1, GCLM, NQO1, HO-1, pNrf2, and protein were significantly increased. Low. (2) compared with the control group, the levels of NQO1mRNA, HO-1mRNA, CATmRNA, SOD1mRNA, Gpx-1mRNA and GCLc mRNA in the C2C12 cells of the inhibitor group decreased significantly, and the expression of NQO1 and GCLM proteins in the cells decreased significantly, and the ROS level of the cells increased significantly. Conclusions  (1) the activation of AMPK by AICAR activates the increase of Nrf2 activation in skeletal muscle C2C12 cells, and then increases the expression of mRNA and protein (SOD1, GCLM, NQO1, NQO1, GSR) in the downstream of Nrf2 (NQO1, HO-1, GSR), and significantly reduces the intracellular level.(2) the inhibition of AMPK by Compound C significantly decreased the mRNA expression of C2C12 cells (NQO1, HO-1, CAT, SOD1, Gpx-1, GCLc) in skeletal muscle, and significantly decreased the expression of protein (NQO1 and GCLc)

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Protective Effect of Dorema glabrum on Induced Oxidative Stress by Diazinon in Hippocampus of Rat

International Journal of Biochemistry Research & Review ◽

10.9734/ijbcrr/2019/v25i330077 ◽

2019 ◽

pp. 1-7

Author(s):

Mina Adampourezare ◽

Parisa Sistani ◽

Homeira Hatami Nemati

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Glutathione Peroxidase ◽

Catalase Activity ◽

Antioxidant Properties ◽

Thiobarbituric Acid ◽

Control Group ◽

Male Wistar Rats ◽

Pre Treatment

Introduction: Diazinon (DZN) administration produces lipid peroxidation as an indicator of oxidative stress in the brain. Some medicinal plants such as Dorema glabrum has antioxidant properties, so can be used as an antioxidant that may protect neurons from oxidative stress. The aim of present study was to investigate the effect of D. glabrum against DZN-induced oxidative stress in hippocampus. Methods: Twenty-four adult male Wistar rats were used in this study. The rats randomly were divided into four groups including a control group, and two groups received different doses of D. glabrum (40 and 80 mg/kg) as pre-treatment for 21 days with DZN (100 mg/Kg) that was injected intraperitoneally (ip) in last day of D. glabrum usage, and one group received only DZN. Thiobarbituric acid reactive substances (TBARS), which are the indicators of lipid peroxidation, and the activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase and catalase) were determined in the ratsʼ hippocampus. Results: Administration of DZN significantly increased TBARS levels and superoxide dismutase activity and decreased glutathione peroxidase activity but there were no significant changes in catalase activity in the hippocampus. Combined D. glabrum and DZN treatment, caused a significant increase in glutathione peroxidase, a significant decrease of TBARS and a significant decrease in superoxide dismutase and again no significant changes in catalase activity in the rats’ hippocampus when compared to the rats treated with DZN. Conclusion: Our study demonstrated that D. glabrum had an amelioratory effect on oxidative stress induced by DZN.

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