Epicatechin and its in vivo metabolite, 3′-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation

2001 ◽  
Vol 354 (3) ◽  
pp. 493-500 ◽  
Author(s):  
Jeremy P. E. SPENCER ◽  
Hagen SCHROETER ◽  
Gunter KUHNLE ◽  
S. Kaila S. SRAI ◽  
Rex M. TYRRELL ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Caspase 3 ◽  
Cell Damage ◽  
Protective Action ◽  
Human Fibroblasts ◽  
Membrane Damage ◽  
Antioxidant Properties

There is considerable current interest in the cytoprotective effects of natural antioxidants against oxidative stress. In particular, epicatechin, a major member of the flavanol family of polyphenols with powerful antioxidant properties in vitro, has been investigated to determine its ability to attenuate oxidative-stress-induced cell damage and to understand the mechanism of its protective action. We have induced oxidative stress in cultured human fibroblasts using hydrogen peroxide and examined the cellular responses in the form of mitochondrial function, cell-membrane damage, annexin-V binding and caspase-3 activation. Since one of the major metabolites of epicatechin in vivo is 3′-O-methyl epicatechin, we have compared its protective effects with that of epicatechin. The results provide the first evidence that 3′-O-methyl epicatechin inhibits cell death induced by hydrogen peroxide and that the mechanism involves suppression of caspase-3 activity as a marker for apoptosis. Furthermore, the protection elicited by 3′-O-methyl epicatechin is not significantly different from that of epicatechin, suggesting that hydrogen-donating antioxidant activity is not the primary mechanism of protection.

scholarly journals Epicatechin and its in vivo metabolite, 3′-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation

2001 ◽  
Vol 354 (3) ◽  
pp. 493 ◽  
Author(s):  
Jeremy P.E. SPENCER ◽  
Hagen SCHROETER ◽  
Gunter KUHNLE ◽  
S. Kaila S. SRAI ◽  
Rex M. TYRRELL ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Caspase 3 ◽  
Human Fibroblasts

scholarly journals Estimation of the Genotoxicityof Hydrogen Peroxide and Antioxidant Actionof Halo Acid by the Method of Dna-Cometwith the Use of the Model of Transplantable Cell Cultures

2018 ◽  
pp. 40-43
Author(s):  
Olga Verle ◽  
Oleg Ostrovskiy ◽  
Valerian Verovskiy ◽  
Galina Dudchenko
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
In Vitro Model ◽  
Cell Damage ◽  
Protective Action ◽  
Genetic Material ◽  
Optimal Level ◽  
Pharmacological Agents ◽  
Vitro Model

In the framework of the study, the degree of defragmentation of DNA by the DNA-comet method is evaluated when exposed to the cell culture of hydrogen peroxide (H2O2), and an in vitro model is developed to evaluate the antioxidant activity of new pharmacological agents. The results of working with cell lines show that the percentage of damage to the genetic material of cells of intact samples does not greatly vary from the method of removing the cellular monolayer from the culture plastic. Concerning the effect of H2O2 as an inducer of oxidative stress on DNA cell damage, the optimal level of DNA defragmentation has been modeled for subsequent studies of the protective action of antioxidants.

Anti-Acute Myeloid Leukemia Activity of Chaetocin, a Novel Epigenetic Drug Inhibitor Inducing Oxidative Stress.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 889-889
Author(s):  
Hassiba Chaib ◽  
Thomas Prebet ◽  
Audrey Restouin ◽  
Remy Castellano ◽  
Sandrine Opi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Caspase 3 ◽  
Hdac Inhibitors ◽  
Oxidative Species ◽  
Acute Myeloid

Abstract Recent studies have highlighted the importance of epigenetic modifications in the pathogenesis of Acute Myeloid Leukemia (AML). This results have been confirmed by the activity of new drug like DNA demethylating agents and histone deacetylase (HDAC) inhibitors in both in vivo and in vitro studies. Recently, Chaetocin, a natural fungal compound, has been identified as the first specific inhibitor of the histone methyltransferase SU(VAR)3–9 which plays a role in heterochromatin gene silencing. In this study, we decided to evaluate Chaetocin as a therapeutic agent in AML in vitro and to explore the related mechanisms. We show that Chaetocin induce dramatic cell death at nanomolar concentrations in U937 and HL60 (97.2% ± 0.4 and 91.6% ± 9 cell death at 100 nM chaetocin, respectively), and to a lesser extend in K562 (67.3% ± 1.6 cell death at 100 nM chaetocin), cell cultures. Cell death occurred at 24 h incubation time which correlated with induction of apoptosis as assessed by Annexin V/7-AAD staining and activation of downstream executioner caspase-3/7. Using transcription low-density array and quantitative RT- PCR, Chaetocin was showed to up-regulate gene transcription such as of the cell cycle inhibitor p21/WAF1 consistent with a role for the targeted SU(VAR)3–9 in heterochromatin gene silencing. In agreement with the recent report of Chaetocin being a promising new antimyeloma agent acting via imposition of oxidative stress, intracellular levels of oxidative species were increased in Chaetocin treated U937 cells in a time- and dose-dependent manner that correlated with induction of cell death. Furthermore, incubation of cells with N-acetyl cysteine, a cell-permeable precursor of intracellular glutathione reductant, prevented chaetocin-induced accumulation of oxidative species, transcription of selected genes (e.g. p21/WAF1), activation of caspase-3, and cell death. Finally, Chaetocin was found to increase the antileukemia activity of HDAC inhibitors and Aracytin, and thus appears as a promising agent for further study as a potential anti-AML therapeutic. Preliminary results obtained in vivo in xenograft models and ex vivo, using blasts of a panel of patients with AML, will be presented.

scholarly journals Astaxanthin as Potential Antioxidant Agent Protects from Accumulation of Heavy-metals in Brain

2017 ◽  
Vol 1 (2) ◽  
Author(s):  
Mohammed Said Moosa Al-Bulish, Changhu Xue, Mostafa I. Waly,
Keyword(s):  
Oxidative Stress ◽  
Heavy Metals ◽  
Hydrogen Peroxide ◽  
Protective Effect ◽  
Neurological Disorders ◽  
Antioxidant Properties ◽  
Body Burden ◽  
Antioxidant Potential ◽  
Antioxidant Agent

Humans are increasingly exposed to heavy-metals from food, water, medicine, vaccines, and cosmetics. The toxicity of heavy-metals in humans is briefly summarized, links the possible causal relationships between a high heavy-metals body burden and a number of neurological disorders including Alzheimer’s, Parkinson and Autism disorders. This study aimed to assess the antioxidant properties of Astaxanthin (ASTA) to determine the effect of orally administered ASTA capability of restrict accumulation and toxicity of heavy-metals in brain of rats. It also, assess against Hydrogen peroxide induced oxidative stress and antioxidant potential properties of ASTA with comparing the affectivity of 5% and 10% of ASTA in increased glutathione-recycling enzymes (GPx oxidation). A significant change was observed as increased glutathione-recycling enzymes (GPx oxidation) of rats and showed a protective effect against accumulation of Aluminum(AL) in rat’s brain tissues. The results of this in-vivo study demonstrated that ASTA 10% is more can affective in restriction of accumulation and toxicity of Al in rate brain and its contented can protects against oxidative-stress.          

scholarly journals The Protective Effects of α-Mangostin Attenuate Sodium Iodate-Induced Cytotoxicity and Oxidative Injury via Mediating SIRT-3 Inactivation via the PI3K/AKT/PGC-1α Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1870
Author(s):  
Chen-Ju Chuang ◽  
Meilin Wang ◽  
Jui-Hsuan Yeh ◽  
Tzu-Chun Chen ◽  
Shang-Chun Tsou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Cell Damage ◽  
Outer Nuclear Layer ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Age Related

It is well known that age-related macular degeneration (AMD) is an irreversible neurodegenerative disease that can cause blindness in the elderly. Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is a part of the pathogenesis of AMD. In this study, we evaluated the protective effect and mechanisms of alpha-mangostin (α-mangostin, α-MG) against NaIO3-induced reactive oxygen species (ROS)-dependent toxicity, which activates apoptosis in vivo and in vitro. MTT assay and flow cytometry demonstrated that the pretreatment of ARPE-19 cells with α-MG (0, 3.75, 7.5, and 15 μM) significantly increased cell viability and reduced apoptosis from NaIO3-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cleaved PARP-1, cleaved caspase-3 protein expression, and enhancement of Bcl-2 protein. Furthermore, pre-incubation of ARPE-19 cells with α-MG markedly inhibited the intracellular ROS and extracellular H2O2 generation via blocking of the abnormal enzyme activities of superoxide dismutase (SOD), the downregulated levels of catalase (CAT), and the endogenous antioxidant, glutathione (GSH), which were regulated by decreasing PI3K-AKT-PGC-1α-STRT-3 signaling in ARPE-19 cells. In addition, our in vivo results indicated that α-MG improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer by inhibiting the expression of cleaved caspase-3 protein. Taken together, our results suggest that α-MG effectively protects human ARPE-19 cells from NaIO3-induced oxidative damage via antiapoptotic and antioxidant effects.

Glial cytotoxicity of low doses of cadmium as a model of heavy metal pollution influence on vertebrates

2020 ◽  
Vol 31 (1) ◽  
pp. 3-10
Author(s):  
V. S. Nedzvetsky ◽  
V. Ya. Gasso ◽  
A. M. Hahut ◽  
I. A. Hasso
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Oxidative Damage ◽  
Cadmium Chloride ◽  
Glioma Cells ◽  
Low Doses ◽  
Genotoxic Effects ◽  
Cadmium Ions

Cadmium is a common transition metal that entails an extremely wide range of toxic effects in humans and animals. The cytotoxicity of cadmium ions and its compounds is due to various genotoxic effects, including both DNA damage and chromosomal aberrations. Some bone diseases, kidney and digestive system diseases are determined as pathologies that are closely associated with cadmium intoxication. In addition, cadmium is included in the list of carcinogens because of its ability to initiate the development of tumors of several forms of cancer under conditions of chronic or acute intoxication. Despite many studies of the effects of cadmium in animal models and cohorts of patients, in which cadmium effects has occurred, its molecular mechanisms of action are not fully understood. The genotoxic effects of cadmium and the induction of programmed cell death have attracted the attention of researchers in the last decade. In recent years, the results obtained for in vivo and in vitro experimental models have shown extremely high cytotoxicity of sublethal concentrations of cadmium and its compounds in various tissues. One of the most studied causes of cadmium cytotoxicity is the development of oxidative stress and associated oxidative damage to macromolecules of lipids, proteins and nucleic acids. Brain cells are most sensitive to oxidative damage and can be a critical target of cadmium cytotoxicity. Thus, oxidative damage caused by cadmium can initiate genotoxicity, programmed cell death and inhibit their viability in the human and animal brains. To test our hypothesis, cadmium cytotoxicity was assessed in vivo in U251 glioma cells through viability determinants and markers of oxidative stress and apoptosis. The result of the cell viability analysis showed the dose-dependent action of cadmium chloride in glioma cells, as well as the generation of oxidative stress (p <0.05). Calculated for 48 hours of exposure, the LD50 was 3.1 μg×ml-1. The rates of apoptotic death of glioma cells also progressively increased depending on the dose of cadmium ions. A high correlation between cadmium concentration and apoptotic response (p <0.01) was found for cells exposed to 3–4 μg×ml-1 cadmium chloride. Moreover, a significant correlation was found between oxidative stress (lipid peroxidation) and induction of apoptosis. The results indicate a strong relationship between the generation of oxidative damage by macromolecules and the initiation of programmed cell death in glial cells under conditions of low doses of cadmium chloride. The presented results show that cadmium ions can induce oxidative damage in brain cells and inhibit their viability through the induction of programmed death. Such effects of cadmium intoxication can be considered as a model of the impact of heavy metal pollution on vertebrates.

Neuroprotective Effects of Extracts from the Radix Curcuma aromatica on H2O2-induced Damage in PC12 Cells

2018 ◽  
Vol 21 (8) ◽  
pp. 571-582 ◽  
Author(s):  
Juxiang Liu ◽  
Lianli Zhang ◽  
Dan Liu ◽  
Baocai Li ◽  
Mi Zhang
Keyword(s):  
Oxidative Stress ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Cell Damage ◽  
Positive Control ◽  
Neuroprotective Activity ◽  
Antioxidant Enzyme Activities ◽  
Morphologic Change ◽  
Neuroprotective Effects ◽  
Etoh Extract

Aim & Objectives: Curcuminoids are characteristic constituents in Curcuma, displaying obviously neuroprotective activities against oxidative stress. As one of the Traditional Chinese Medicines from Curcuma, the radix of Curcuma aromatica is also rich in those chemicals, but its neuroprotective activity and mechanism remain unknown. The aim of the current study is to evaluate the neuroprotective effects of extracts from the radix of C. aromatica (ECAs) on H2O2-damaged PC12 cells. Material and Methods: The model of oxidative stress damage was established by treatment of 400 µM H2O2 on PC12 to induce cell damage. After the treatment of ECWs for 24 h, the cell viability, LDH, SOD, CAT and GSH were measured to evaluate the neuroprotection of ECAs on that model. The potential action mechanism was studied by measurement of level of ROS, cell apoptosis rate, mitochondrial membrane potential (MMP), morphologic change, the intracellular Ca2+ content (F340/F380) and the expressions of Bcl-2, Bax and Caspase-3. Additionally, the constituents from tested extracts were analyzed by HPLC-DAD-Q-TOF-MS method. Results: Compared with a positive control, Vitamin E, 10 µg/ml of 95% EtOH extract (HCECA) and 75% EtOH extract (MCECA) can markedly increase the rate of cell survival and enhance the antioxidant enzyme activities of SOD, CAT, increase the levels of GSH, decrease LDH release and the level of ROS, attenuate the intracellular Ca2+ overloading, reduce the cell apoptotic rate and stabilize MMP, down-regulate Bcl-2 expression, up-regulate Bax and caspase-3 expression, and improve the change of cell morphology. The chemical analysis showed that diarylheptanoids and sesquiterpenoids are the major chemicals in tested extracts and the former were richer in HCECA and MCECA than others. Conclusions: These findings indicated that the effects of HCECA and MCECA on inhibiting the cells damage induced by H2O2 in PC12 are better than other extracts from the radix of C. aromatica, and the active constituents with neuroprotective effects consisting in those two active extracts are diarylheptanoids.

scholarly journals Autophagy impairment as a key feature for acetaminophen-induced ototoxicity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tong Zhao ◽  
Tihua Zheng ◽  
Huining Yu ◽  
Bo Hua Hu ◽  
Bing Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Lysosomal Enzymes ◽  
Apoptotic Cell ◽  
Cell Damage ◽  
Treatment Strategies ◽  
Explant Culture ◽  
Apoptotic Cell Death ◽  
Lysosomal Dysfunction ◽  
Autophagic Degradation

AbstractMacroautophagy/autophagy is a highly conserved self-digestion pathway that plays an important role in cytoprotection under stress conditions. Autophagy is involved in hepatotoxicity induced by acetaminophen (APAP) in experimental animals and in humans. APAP also causes ototoxicity. However, the role of autophagy in APAP-induced auditory hair cell damage is unclear. In the present study, we investigated autophagy mechanisms during APAP-induced cell death in a mouse auditory cell line (HEI-OC1) and mouse cochlear explant culture. We found that the expression of LC3-II protein and autophagic structures was increased in APAP-treated HEI-OC1 cells; however, the degradation of SQSTM1/p62 protein, the yellow puncta of mRFP-GFP-LC3 fluorescence, and the activity of lysosomal enzymes decreased in APAP-treated HEI-OC1 cells. The degradation of p62 protein and the expression of lysosomal enzymes also decreased in APAP-treated mouse cochlear explants. These data indicate that APAP treatment compromises autophagic degradation and causes lysosomal dysfunction. We suggest that lysosomal dysfunction may be directly responsible for APAP-induced autophagy impairment. Treatment with antioxidant N-acetylcysteine (NAC) partially alleviated APAP-induced autophagy impairment and apoptotic cell death, suggesting the involvement of oxidative stress in APAP-induced autophagy impairment. Inhibition of autophagy by knocking down of Atg5 and Atg7 aggravated APAP-induced ER and oxidative stress and increased apoptotic cell death. This study provides a better understanding of the mechanism responsible for APAP ototoxicity, which is important for future exploration of treatment strategies for the prevention of hearing loss caused by ototoxic medications.

scholarly journals Ethanol Extract of Maclura tricuspidata Fruit Protects SH-SY5Y Neuroblastoma Cells against H2O2-Induced Oxidative Damage via Inhibiting MAPK and NF-κB Signaling

2021 ◽  
Vol 22 (13) ◽  
pp. 6946
Author(s):  
Weishun Tian ◽  
Suyoung Heo ◽  
Dae-Woon Kim ◽  
In-Shik Kim ◽  
Dongchoon Ahn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Cell Damage ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Biologically Active ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Neuroprotective Effects

Free radical generation and oxidative stress push forward an immense influence on the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Maclura tricuspidata fruit (MT) contains many biologically active substances, including compounds with antioxidant properties. The current study aimed to investigate the neuroprotective effects of MT fruit on hydrogen peroxide (H2O2)-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H2O2. First, the chemical composition and free radical scavenging properties of MT were analyzed. MT attenuated oxidative stress-induced damage in cells based on the assessment of cell viability. The H2O2-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release was ameliorated by MT pretreatment. MT also promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). MT pretreatment was associated with an increase in the expression of neuronal genes downregulated by H2O2. Mechanistically, MT dramatically suppressed H2O2-induced Bcl-2 downregulation, Bax upregulation, apoptotic factor caspase-3 activation, Mitogen-activated protein kinase (MAPK) (JNK, ERK, and p38), and Nuclear factor-κB (NF-κB) activation, thereby preventing H2O2-induced neurotoxicity. These results indicate that MT has protective effects against H2O2-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.

Sign in / Sign up

Export Citation Format

Share Document