scholarly journals Curcumin Suppresses the Lipid Accumulation and Oxidative Stress Induced by Benzo[a]pyrene Toxicity in HepG2 Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1314
Author(s):  
Seung-Cheol Lee ◽  
Seung-Cheol Jee ◽  
Min Kim ◽  
Soee Kim ◽  
Min Kyoung Shin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome P450 ◽  
Cell Viability ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Nuclear Translocation ◽  
The Body ◽  
Ros Generation ◽  
Related Factor ◽  
And Oxidative Stress

Benzo[a]pyrene (B[a]P) is a potentially hepatotoxic group-1 carcinogen taken up by the body through ingestion of daily foods. B[a]P is widely known to cause DNA and protein damages, which are closely related to cell transformation. Accordingly, studies on natural bioactive compounds that attenuate such chemical-induced toxicities have significant impacts on public health. This study aimed to uncover the mechanism of curcumin, the major curcuminoid in turmeric (Curcuma longa), in modulating the lipid accumulation and oxidative stress mediated by B[a]P cytotoxicity in HepG2 cells. Curcumin treatment reduced the B[a]P-induced lipid accumulation and reactive oxygen spicies (ROS) upregulation and recovered the cell viability. Cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) and Cytochrome P450 subfamily B polypeptide 1 (CYP1B1) downregulation resulting from decreased aryl hydrocarbon receptor (AhR) translocation into nuclei attenuated the effects of B[a]P-induced lipid accumulation and repressed cell viability, respectively. Moreover, the curcumin-induced reduction in ROS generation decreased the nuclear translocation of Nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of phase-II detoxifying enzymes. These results indicate that curcumin suppresses B[a]P-induced lipid accumulation and ROS generation which can potentially induce nonalcoholic fatty liver disease (NAFLD) and can shed a light on the detoxifying effect of curcumin.

Hydrogen peroxide and quercetin induced changes on cell viability, apoptosis and oxidative stress in HepG2 cells

2020 ◽  
Vol 01 ◽  
Author(s):  
Ayşe Mine Yılmaz ◽  
Gökhan Biçim ◽  
Kübra Toprak ◽  
Betül Karademir Yılmaz ◽  
Irina Milisav ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Hydrogen Peroxide ◽  
Cell Viability ◽  
Hepg2 Cells ◽  
Proteasome Activity ◽  
Cell Cycle Phases ◽  
Induced Changes ◽  
And Oxidative Stress ◽  
Quercetin Treatment

Background: Different cellular responses influence the progress of cancer. In this study, we have investigated the effect of hydrogen peroxide and quercetin induced changes on cell viability, apoptosis and oxidative stress in human hepatocellular carcinoma (HepG2) cells. Methods: The effects of hydrogen peroxide and quercetin on cell viability, cell cycle phases and oxidative stress related cellular changes were investigated. Cell viability was assessed by WST-1 assay. Apoptosis rate, cell cycle phase changes and oxidative stress were measured by flow cytometry. Protein expressions of p21, p27, p53, NF-Kβ-p50 and proteasome activity were determined by Western blot and fluorometry, respectively. Results: Hydrogen peroxide and quercetin treatment resulted in decreased cell viability and increased apoptosis in HepG2 cells. Proteasome activity was increased by hydrogen peroxide but decreased by quercetin treatment. Conclusion: Both agents resulted in decreased p53 protein expression and increased cell death by different mechanisms regarding proteostasis and cell cycle phases.

scholarly journals Kaempferol and Kaempferide Attenuate Oleic Acid-Induced Lipid Accumulation and Oxidative Stress in HepG2 Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8847
Author(s):  
Fangfang Tie ◽  
Jin Ding ◽  
Na Hu ◽  
Qi Dong ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oleic Acid ◽  
Lipid Metabolism ◽  
Western Blot ◽  
Blot Analysis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Western Blot Analysis ◽  
Heme Oxygenase 1 ◽  
And Oxidative Stress

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases which lacks ideal treatment options. Kaempferol and kaempferide, two natural flavonol compounds isolated from Hippophae rhamnoides L., were reported to exhibit a strong regulatory effect on lipid metabolism, for which the mechanism is largely unknown. In the present study, we investigated the effects of kaempferol and kaempferide on oleic acid (OA)-treated HepG2 cells, a widely used in vitro model of NAFLD. The results indicated an increased accumulation of lipid droplets and triacylglycerol (TG) by OA, which was attenuated by kaempferol and kaempferide (5, 10 and 20 μM). Western blot analysis demonstrated that kaempferol and kaempferide reduced expression of lipogenesis-related proteins, including sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1). Expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding proteins β (C/EBPβ), two adipogenic transcription factors, was also decreased by kaempferol and kaempferide treatment. In addition, western blot analysis also demonstrated that kaempferol and kaempferide reduced expression of heme oxygenase-1 (HO-1) and nuclear transcription factor-erythroid 2-related factor 2 (Nrf2). Molecular docking was performed to identify the direct molecular targets of kaempferol and kaempferide, and their binding to SCD-1, a critical regulator in lipid metabolism, was revealed. Taken together, our findings demonstrate that kaempferol and kaempferide could attenuate OA-induced lipid accumulation and oxidative stress in HepG2 cells, which might benefit the treatment of NAFLD.

scholarly journals Safflor Yellow B Attenuates Ischemic Brain Injury via Downregulation of Long Noncoding AK046177 and Inhibition of MicroRNA-134 Expression in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Chaoyun Wang ◽  
Hongzhi Wan ◽  
Qiaoyun Wang ◽  
Hongliu Sun ◽  
Yeying Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Ischemia Reperfusion ◽  
Cell Activity ◽  
Neuronal Injury ◽  
The Body ◽  
Ros Generation ◽  
Related Factor ◽  
Cell Respiration ◽  
Oxidative Balance

Stroke breaks the oxidative balance in the body and causes extra reactive oxygen species (ROS) generation, leading to oxidative stress damage. Long noncoding RNAs (lncRNAs) and microRNAs play pivotal roles in oxidative stress-mediated brain injury. Safflor yellow B (SYB) was able to effectively reduce ischemia-mediated brain damage by increasing antioxidant capacity and inhibiting cell apoptosis. In this study, we investigated the putative involvement of lncRNA AK046177 and microRNA-134 (miR-134) regulation in SYB against ischemia/reperfusion- (I/R-) induced neuronal injury. I/R and oxygen-glucose deprivation/reoxygenation (OGD/R) were established in vivo and in vitro. Cerebral infarct volume, neuronal apoptosis, and protein expression were detected. The effects of SYB on cell activity, cell respiration, nuclear factor erythroid 2-related factor 2 (Nrf2), antioxidant enzymes, and ROS were evaluated. I/R or OGD/R upregulated the expression of AK046177 and miR-134 and subsequently inhibited the activation and expression of CREB, which caused ROS generation and brain/cell injury. SYB attenuated the effects of AK046177, inhibited miR-134 expression, and promoted CREB activation, which in turn promoted Nrf2 expression, and then increased antioxidant capacities, improved cell respiration, and reduced apoptosis. We suggested that the antioxidant effects of SYB were driven by an AK046177/miR-134/CREB-dependent mechanism that inhibited this pathway, and that SYB has potential use in reducing or possibly preventing I/R-induced neuronal injury.

scholarly journals Gentiopicroside Ameliorates Oxidative Stress and Lipid Accumulation through Nuclear Factor Erythroid 2-Related Factor 2 Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Meiyu Jin ◽  
Haihua Feng ◽  
Yue Wang ◽  
Siru Yan ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Regulatory Element ◽  
Cell Counting ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Akt Inhibitor

The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is closely related to the alleviation of nonalcoholic fatty liver disease (NAFLD) by regulating oxidative stress and lipid homeostasis. Gentiopicroside (GPS), an iridoid glycoside found in the Gentianaceae, possesses anti-inflammatory and antioxidant effects. However, the protective effects of GPS on lipid accumulation and oxidative damage have not been investigated thoroughly in free fatty acid- (FFA-) induced HepG2 cells and tyloxapol- (Ty-) induced hyperlipidemia mice. Cell counting kit-8 assays, Oil Red O staining, Western blotting analysis, extraction of nuclear and cytosolic proteins, and biochemical index assay were employed to explore the mechanisms by which GPS exerts a protective effect on FFA-induced HepG2 cells and Ty-induced hyperlipidemia mouse model. This paper demonstrates that GPS could effectively alleviate NAFLD by elevating cell viability, reducing fatty deposition, downregulating TG, and activating nucleus Nrf2 in FFA-induced HepG2 cells. Meanwhile, GPS significantly regulated the activation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, Nrf2 antioxidant pathway, peroxisome proliferator-activated receptor α (PPARα), and GPS-inhibited sterol regulatory element-binding protein-1c (SREBP-1c) expression in FFA-stimulated lipid accumulation of HepG2 cells and Ty-treated mice. Interestingly, we highlight that PI3K/AKT inhibitor (LY294002) markedly increased the expression of Nrf2 antioxidant pathway, PPARα, and downregulated SREBP-1c in FFA-stimulated HepG2 cells. For these reasons, we found that the deletion of Nrf2 could lose the protective effects of GPS on the Nrf2 antioxidant pathway and PPARα activation and SREBP-1c inactivation in FFA-stimulated HepG2 cells and Ty-treated mice. GPS treatment had no effect on abnormal lipogenesis and antioxidant enzymes in Ty-induced Nrf2-/- mice. This work gives a new explanation that GPS may be a useful therapeutic strategy for NAFLD through upregulation of the Nrf2 antioxidant pathway, which can alleviate oxidative damage and lipid accumulation.

Dihydromyricetin ameliorates oleic acid-induced lipid accumulation in L02 and HepG2 cells by inhibiting lipogenesis and oxidative stress

Life Sciences ◽  
2016 ◽  
Vol 157 ◽  
pp. 131-139 ◽  
Author(s):  
Caifeng Xie ◽  
Zhen Chen ◽  
Chengfu Zhang ◽  
Xin Xu ◽  
Jiangbo Jin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oleic Acid ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
And Oxidative Stress

Celastrol ameliorates acetaminophen-induced oxidative stress and cytotoxicity in HepG2 cells

2017 ◽  
Vol 37 (7) ◽  
pp. 742-751 ◽  
Author(s):  
AT Jannuzzi ◽  
M Kara ◽  
B Alpertunga
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Hepg2 Cells ◽  
Membrane Integrity ◽  
Neutral Red ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tripterygium Wilfordii Hook F ◽  
Cell Membrane Integrity ◽  
And Oxidative Stress

Acetaminophen (APAP) is the most commonly used analgesic and antipyretic drug in the world. However, hepatotoxicity caused by APAP overdose is the most frequent cause of acute liver failure worldwide and oxidative stress involved in the pathogenesis of APAP hepatotoxicity. Celastrol is a natural triterpenoid derived from Tripterygium wilfordii Hook F. that exhibits antioxidant, anti-inflammatory, and antitumor activities. In this study, we aimed to investigate the potential ameliorative effects of celastrol against APAP-induced cytotoxicity and oxidative stress. Human hepatocellular carcinoma cells (HepG2) were incubated with 20 mM of APAP for 24 h and posttreated with 50 nM, 100 nM, or 200 nM of celastrol for a further 24 h. The methylthiazolyldiphenyl-tetrazolium bromide, lactate dehydrogenase, and neutral red uptake assays showed celastrol posttreatments recovered cell viability and cell membrane integrity in a concentration-dependent manner. Celastrol posttreatments exerted a significant increase in the glutathione content and a decrease in the malondialdehyde and protein carbonylation levels. Also, celastrol posttreatments attenuated the APAP-induced oxidative stress by raising glutathione peroxidase, glutathione reductase, and catalase activities. However, superoxide dismutase activity did not change. In conclusion, celastrol treatment may improve cell viability and increase cellular antioxidant defense in HepG2 cells. These results suggest that celastrol may have the potential to ameliorate the APAP-induced oxidative stress and cytotoxicity.

scholarly journals Oltipraz Prevents High Glucose-Induced Oxidative Stress and Apoptosis in RSC96 Cells through the Nrf2/NQO1 Signalling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zengxin Jiang ◽  
Mengxuan Bian ◽  
Jingping Wu ◽  
Defang Li ◽  
Lei Ding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Flow Cytometry ◽  
Cell Viability ◽  
High Glucose ◽  
Control Flow ◽  
Cell Counting ◽  
Ros Generation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). Schwann cell (SC) apoptosis contributes to the occurrence and development of DPN. Effective drugs to prevent SC apoptosis are required to relieve and reverse peripheral nerve injury caused by DM. Oltipraz [4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione], an agonist of nuclear factor erythroid derived-2-related factor 2 (Nrf2), exerts strong effect against oxidative stress in animal models or clinical patients in certain diseases, including heart failure, acute kidney injury, and liver injury. The aim of the present study was to determine the effectiveness of oltipraz in preventing SC apoptosis induced by high glucose levels. RSC96 cells pretreated with oltipraz were cultured in high-glucose medium (50 mM glucose) for 24 h, and cells cultured in medium containing 5 mM glucose were used as the control. Flow cytometry was used to evaluate the degree of apoptosis. A Cell Counting Kit-8 assay was used to assess cell viability. The mitochondrial membrane potential was assessed using JC-1 staining, and reactive oxygen species (ROS) generation was measured using 20,70-dichlorodihydrofluorescein diacetate staining. In addition, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) levels were also evaluated using the corresponding kits. Flow cytometry was subsequently used to detect apoptosis, and western blotting was used to measure the expression levels of nuclear factor erythroid derived-2-related factor 2 and NADPH quinone oxidoreductase 1. The results showed that high glucose concentration increased oxidative stress and apoptosis in RSC96 cells. Oltipraz improved cell viability and reduced apoptosis of RSC96 cells in the high glucose environment. Additionally, oltipraz exhibited a significant antioxidative effect, as shown by the decrease in MDA levels, increased SOD levels, and reduced ROS generation in RSC96 cells. The results of the present study suggest that oltipraz exhibits potential as an effective drug for treatment with DPN.

scholarly journals Tebuconazole Fungicide Induces Lipid Accumulation and Oxidative Stress in HepG2 Cells

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2242
Author(s):  
Hyuk-Cheol Kwon ◽  
Do-Hyun Kim ◽  
Chang-Hee Jeong ◽  
Yea-Ji Kim ◽  
Jong-Hyun Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Nuclear Translocation ◽  
Liver Toxicity ◽  
Fatty Acid Transport ◽  
Peroxisome Proliferator ◽  
Lipid Uptake ◽  
Alcoholic Fatty Liver

Tebuconazole (TEB), a triazole fungicide, is frequently applied to agriculture for the increase of food production. Although TEB causes liver toxicity, its effects on cellular lipid accumulation are rarely investigated. Therefore, this study aimed to study the effects of TEB on lipid metabolism and accumulation in HepG2 cells. HepG2 cells were exposed to 0–320 µM TEB for 1–24 h. TEB (20–80 µM, 24 h)-treated cells showed lipid accumulation. Further, TEB (20–80 µM, 1–12 h) increased the nuclear translocation of peroxisome proliferator-activated receptors and the expression of lipid uptake and oxidation-related markers such as cluster of differentiation 36, fatty acid transport protein (FATP) 2, FATP5, and carnitine palmitoyltransferase 1. Oxidative stress levels in TEB-treated cells (20–80 µM, 24 h) were higher, compared to those in the control. TEB (20–80 µM, 24 h) also induced the loss of mitochondrial membrane potential and lower levels of microsomal triglyceride transfer protein in the cells. Thus, TEB can induce lipid accumulation by altering the expression of lipid-metabolizing molecules and can therefore impair lipid metabolism. Our data suggest that human exposure to TEB may be a risk factor for non-alcoholic fatty liver disease.

scholarly journals Fucoxanthin Inhibits Lipopolysaccharide-Induced Inflammation and Oxidative Stress by Activating Nuclear Factor E2-Related Factor 2 in Macrophages

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 116-116
Author(s):  
Mi-Bo Kim ◽  
Hyunju Kang ◽  
Ji-Young Lee
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Nuclear Translocation ◽  
Radical Scavenging ◽  
Raw 264.7 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Underlying Mechanisms ◽  
Antioxidant Effects ◽  
And Oxidative Stress

Abstract Objectives Anti-inflammatory and antioxidant effects of fucoxanthin (FCX), a carotenoid present in edible brown seaweeds, have been suggested. However, the underlying mechanisms have not been fully understood. The objectives of this study were to determine whether FCX can inhibit lipopolysaccharide (LPS)-induced inflammation and oxidative stress and to elucidate the underlying mechanisms in macrophages. Methods Cytotoxicity of FCX (0–15 μM) was measured in RAW 264.7 macrophage. The effects of the FCX on LPS-induced inflammatory cytokine and antioxidant gene expression were determined in RAW 264.7 macrophages by quantitative realtime PCR, Western blot, and enzyme-linked immunosorbent assays. Cellular reactive oxygen species (ROS) accumulation was measured in LPS-induced RAW 264.7 macrophage. The antioxidant capacity was also determined by 2,2′-azinobis (3-ethylbenzothiazoline 6-sulfonate) (ABTS) radical scavenging activity expressed by trolox equivalent antioxidant capacity (TEAC). Also, a potential role of phosphatidylinositol 3-kinase (PI3K)/nuclear factor E2-related factor 2 (NRF2) axis, a crucial pathway in endogenous antioxidant defense, in the FCX effects was evaluated. Results Cells treated with 5 μM FCX were 90%<viable. LPS significantly increased mRNA levels of interleukin (Il)-6, Il-1β, and tumor necrosis factor α (Tnf) as well as TNFα secretion, which were significantly decreased by FCX. Elevated levels of cellular ROS levels by LPS were abolished by FCX with a concomitant increase in the expression of antioxidant enzymes. ABTS assay demonstrated that FCX had a stronger free radical scavenging property (57.6 TEAC μM/100 μM). Also, FCX significantly increased Nrf2 and heme oxygenase 1 expression compared to LPS control. LPS increased the nuclear translocation of NRF2, which was further increased by FCX. Interestingly, LY294002, an inhibitor of PI3K, noticeably decreased the effect of FCX on NRF2 nuclear translocation. Conclusions FCX exerts anti-inflammatory and antioxidant effects by the activation of NRF2 in LPS-induced macrophages. The increase in NRF2 nuclear translocation is mediated, at least in part, through the PI3K pathway. Funding Sources This study was supported by National Research Foundation of Korea (2019R1A6A3A03032678).

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