Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20 Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1β, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury.

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Acrylamide Exposure and Oxidative DNA Damage, Lipid Peroxidation and Fasting Plasma Glucose Alteration: Association and Mediation Analyses in Chinese Urban Adults

10.2337/figshare.12076134 ◽

2020 ◽

Author(s):

Bin Wang ◽

Weihong Qiu ◽

Shijie Yang ◽

Limin Cao ◽

Chunmei Zhu ◽

...

Keyword(s):

Lipid Peroxidation ◽

Dna Damage ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Oxidative Dna Damage ◽

Adult Population ◽

Prostaglandin F2α ◽

Mediation Analyses ◽

Mediating Role ◽

Fasting Plasma

<a>OBJECTIVE: </a>Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation and fasting plasma glucose (FPG) alteration, and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG. RESEARCH DESIGN AND METHODS: FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxy-guanosine, 8-OHdG), lipid peroxidation (8-iso-prostaglandin-F2α, 8-iso-PGF2α) and acrylamide exposure (N-acetyl-S-(2-carbamoylethyl)-L-cysteine, AAMA; N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, GAMA) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis. RESULTS: We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α and FPG (except GAMA with FPG), and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, ΣUAAM (AAMA+GAMA) or 8-iso-PGF2α was associated with a 0.17-, 0.15- or 0.23-mmol/L increase in FPG, respectively (P or/and P trend<0.05). Each 1% increase in AAMA, GAMA or ΣUAAM was associated with a 0.19%, 0.27% or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48% or 0.44% increase in 8-iso-PGF2α, respectively (P and P trend<0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA and ΣUAAM associated-FPG increases, respectively. CONCLUSIONS: Exposure of general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation.

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Protective effects of sesame oil on 4-NQO-induced oxidative DNA damage and lipid peroxidation in rats

Drug and Chemical Toxicology ◽

10.3109/01480541003782310 ◽

2011 ◽

Vol 34 (2) ◽

pp. 116-119 ◽

Cited By ~ 7

Author(s):

Ponnan Arumugam ◽

Samiraj Ramesh

Keyword(s):

Lipid Peroxidation ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Sesame Oil ◽

Protective Effects

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Oxidative DNA damage and inflammatory responses in cultured human cells and in humans exposed to traffic-related particles

International Journal of Hygiene and Environmental Health ◽

10.1016/j.ijheh.2013.03.002 ◽

2014 ◽

Vol 217 (1) ◽

pp. 23-33 ◽

Cited By ~ 86

Author(s):

Udomratana Vattanasit ◽

Panida Navasumrit ◽

Man Bahadur Khadka ◽

Jantamas Kanitwithayanun ◽

Jeerawan Promvijit ◽

...

Keyword(s):

Dna Damage ◽

Oxidative Dna Damage ◽

Inflammatory Responses ◽

Human Cells ◽

Cultured Human Cells

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Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity

Materials ◽

10.3390/ma10121427 ◽

2017 ◽

Vol 10 (12) ◽

pp. 1427 ◽

Cited By ~ 25

Author(s):

Agmal Scherzad ◽

Till Meyer ◽

Norbert Kleinsasser ◽

Stephan Hackenberg

Keyword(s):

Dna Damage ◽

Zinc Oxide ◽

Mammalian Cells ◽

Oxidative Dna Damage ◽

Molecular Mechanisms ◽

Consumer Products ◽

Zno Nps ◽

Cytotoxic Effects

Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival.

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Associations of propylene oxide exposure with fasting plasma glucose and diabetes: Roles of oxidative DNA damage and lipid peroxidation

Environmental Pollution ◽

10.1016/j.envpol.2021.118453 ◽

2021 ◽

pp. 118453

Author(s):

Wei Liu ◽

Bin Wang ◽

Shijie Yang ◽

Tao Xu ◽

Linling Yu ◽

...

Keyword(s):

Lipid Peroxidation ◽

Dna Damage ◽

Propylene Oxide ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Oxidative Dna Damage ◽

Fasting Plasma

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Gamma Radiation-Induced Disruption of Cellular Junctions in HUVECs Is Mediated through Affecting MAPK/NF-κB Inflammatory Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1486232 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

H. Wang ◽

R. Chandra Segaran ◽

L. Y. Chan ◽

Aref A. M. Aladresi ◽

A. Chinnathambi ◽

...

Keyword(s):

Gamma Radiation ◽

Cell Viability ◽

Gamma Irradiation ◽

Mapk Pathway ◽

Umbilical Vein ◽

Mitogen Activated Protein Kinase ◽

Migration Ability ◽

Protein Levels ◽

Cellular Junctions ◽

Radiation Induced

Ionizing radiation-induced cardiovascular diseases (CVDs) have been well documented. However, the mechanisms of CVD genesis are still not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were exposed to gamma irradiation at different doses ranging from 0.2 Gy to 5 Gy. Cell viability, migration ability, permeability, oxidative and nitrosative stresses, inflammation, and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway activation were evaluated postirradiation. It was found that gamma irradiation at doses ranging from 0.5 Gy to 5 Gy inhibited the migration ability of HUVECs without any significant effects on cell viability at 6 h and 24 h postirradiation. The decreased transendothelial electrical resistance (TEER), increased permeability, and disruption of cellular junctions were observed in HUVECs after gamma irradiation accompanied by the lower levels of junction-related proteins such as ZO-1, occludin, vascular endothelial- (VE-) cadherin, and connexin 40. The enhanced oxidative and nitrosative stresses, e.g., ROS and NO2- levels and inflammatory cytokines IL-6 and TNF-α were demonstrated in HUVECs after gamma irradiation. Western blot results showed that protein levels of mitogen-activated protein kinase (MAPK) pathway molecules p38, p53, p21, and p27 increased after gamma irradiation, which further induced the activation of the NF-κB pathway. BAY 11-7085, an inhibitor of NF-κB activation, was demonstrated to partially block the effects of gamma radiation in HUVECs examined by TEER and FITC-dextran permeability assay. We therefore concluded that the gamma irradiation-induced disruption of cellular junctions in HUVECs was through the inflammatory MAPK/NF-κB signaling pathway.

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