Apoptosis in HepG2 cells induced by zinc pyrithione via mitochondrial dysfunction pathway: Involvement of zinc accumulation and oxidative stress

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.

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Autophagy mitigates ethanol-induced mitochondrial dysfunction and oxidative stress in esophageal keratinocytes

PLoS ONE ◽

10.1371/journal.pone.0239625 ◽

2020 ◽

Vol 15 (9) ◽

pp. e0239625

Author(s):

Prasanna M. Chandramouleeswaran ◽

Manti Guha ◽

Masataka Shimonosono ◽

Kelly A. Whelan ◽

Hisatsugu Maekawa ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

And Oxidative Stress

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One Week of CDAHFD Induces Steatohepatitis and Mitochondrial Dysfunction with Oxidative Stress in Liver

International Journal of Molecular Sciences ◽

10.3390/ijms22115851 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5851

Author(s):

Takehito Sugasawa ◽

Seiko Ono ◽

Masato Yonamine ◽

Shin-ichiro Fujita ◽

Yuki Matsumoto ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

Early Stage ◽

Droplet Deposition ◽

Nonalcoholic Fatty Liver ◽

Stress Markers ◽

Mitochondrial Dna Copy Number ◽

Short Period ◽

And Oxidative Stress

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.

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Aclonifen causes developmental abnormalities in zebrafish embryos through mitochondrial dysfunction and oxidative stress

The Science of The Total Environment ◽

10.1016/j.scitotenv.2021.145445 ◽

2021 ◽

Vol 771 ◽

pp. 145445

Author(s):

Jin-Young Lee ◽

Hahyun Park ◽

Whasun Lim ◽

Gwonhwa Song

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Zebrafish Embryos ◽

Developmental Abnormalities ◽

And Oxidative Stress

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Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽

10.3390/antiox10020229 ◽

2021 ◽

Vol 10 (2) ◽

pp. 229

Author(s):

JunHyuk Woo ◽

Hyesun Cho ◽

YunHee Seol ◽

Soon Ho Kim ◽

Chanhyeok Park ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Computational Models ◽

Neuronal Damage ◽

Living Organism ◽

The Body ◽

Mitochondrial Functions ◽

A Cell ◽

The Brain ◽

And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

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The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

Human & Experimental Toxicology ◽

10.1177/0960327115627688 ◽

2016 ◽

Vol 35 (12) ◽

pp. 1252-1263 ◽

Cited By ~ 23

Author(s):

SS Palabiyik ◽

E Karakus ◽

Z Halici ◽

E Cadirci ◽

Y Bayir ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Hepg2 Cells ◽

Folk Medicine ◽

Hepatoprotective Activity ◽

High Dose ◽

Protective Effects ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

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Chronic Oxidative Stress, Mitochondrial Dysfunction, Nrf2 Activation and Inflammation in the Hippocampus Accompany Heightened Systemic Inflammation and Oxidative Stress in an Animal Model of Gulf War Illness

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2017.00182 ◽

2017 ◽

Vol 10 ◽

Cited By ~ 27

Author(s):

Geetha A. Shetty ◽

Bharathi Hattiangady ◽

Dinesh Upadhya ◽

Adrian Bates ◽

Sahithi Attaluri ◽

...

Keyword(s):

Oxidative Stress ◽

Animal Model ◽

Mitochondrial Dysfunction ◽

Systemic Inflammation ◽

Gulf War ◽

Gulf War Illness ◽

Chronic Oxidative Stress ◽

Nrf2 Activation ◽

And Oxidative Stress

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

International Journal of Molecular Sciences ◽

10.3390/ijms22168847 ◽

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.

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