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

2011 ◽  
Vol 34 (2) ◽  
pp. 116-119 ◽  
Author(s):  
Ponnan Arumugam ◽  
Samiraj Ramesh
Keyword(s):  
Lipid Peroxidation ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Sesame Oil ◽  
Protective Effects

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

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><b>OBJECTIVE: </b></a>Acrylamide exposure from daily-consumed food has raised global concern.<b> </b>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. <p><b>RESEARCH DESIGN AND METHODS:</b> 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.</p> <p><b>RESULTS:</b> 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 (<i>P </i>or/and<i> P trend</i><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 (<i>P </i>and<i> P trend</i><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.</p> <p><b>CONCLUSIONS:</b> 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.<b></b></p>

ID: 140: KLOTHO, AN ANTI-AGING MOLECULE, REGULATES ALVEOLAR EPITHELIAL CELL MTDNA DAMAGE AND APOPTOSIS

2016 ◽  
Vol 64 (4) ◽  
pp. 961.1-961
Author(s):  
S Kim ◽  
P Cheresh ◽  
RP Jablonski ◽  
DW Kamp ◽  
M Eren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Oxidative Dna Damage ◽  
Alveolar Epithelial Cell ◽  
Premature Aging ◽  
Protective Effects ◽  
Mtdna Damage ◽  
Alveolar Epithelial

RationaleConvincing evidence has emerged that impaired alveolar epithelial cell (AEC) injury and repair resulting from ‘exaggerated’ lung aging and mitochondrial dysfunction are critical determinants of the lung fibrogenic potential of toxic agents, including asbestos fibers, but the mechanisms underlying these findings is unknown. We showed that the extent of AEC mitochondrial DNA (mtDNA) damage and apoptosis are critical determinants of asbestos-induced pulmonary fibrosis (Cheresh et al AJRCMB 2014, Kim et al JBC 2014). Klotho is an age-inhibiting gene and Klotho-deficient mice demonstrate a premature aging phenotype that includes a reduced lifespan, arteriosclerosis, and lung oxidative DNA damage, and that Klotho attenuates hyperoxic-induced AEC DNA damage and apoptosis (Ravikumar et al AJP-Lung 2014). We reason that Klotho has an important role in limiting pulmonary fibrosis by protecting the AECs from oxidative stress.MethodsQuantitative PCR-based measurement of mtDNA damage was assessed following transient transfection with wild-type Klotho, Klotho siRNA or AKT siRNA in A549 and/or MLE-12 cells for 48 hrs followed by exposure to either amosite asbestos (25 µg/cm2) or H2O2 (200 µM) for 24 hrs. Apoptosis was assessed by cleaved caspase-9/3 levels and DNA fragmentation assay. Murine pulmonary fibrosis was analyzed in male 8–10 week old WT (C3H/C57B6J) mice or Klotho heterozygous knockout (Kl+/−) mice following intratracheal instillation of a single dose of 100 µg crocidolite asbestos or titanium dioxide (negative control) using histology (fibrosis score by Masson's trichrome staining) and lung collagen (Sircoll assay).ResultsCompared to control, amosite asbestos or H2O2 reduces Klotho mRNA/protein expression. Notably, silencing of Klotho promotes oxidative stress-induced AEC mtDNA damage and apoptosis whereas Klotho-enforced expression (EE) and Euk-134, a mitochondrial ROS scavenger, are protective. Interestingly, Kl+/− mice have increased asbestos-induced lung fibrosis. Also, we find that inhibition or silencing of AKT augments oxidant-induced AEC mtDNA damage and apoptosis.ConclusionsOur data demonstrate a crucial role for AEC AKT signaling in mediating the mtDNA damage protective effects of Klotho. Given the importance of AEC aging and apoptosis in pulmonary fibrosis, we reason that Klotho/AKT axis is an innovative therapeutic target for preventing common lung diseases of aging (i.e. IPF, COPD, lung cancer, etc.) for which more effective management regimens are clearly needed.FundingNIH-RO1 ES020357-01A1 (DK) and VA Merit (DK).

scholarly journals N6-Furfuryladenine is protective in Huntington’s disease models by signaling huntingtin phosphorylation

2018 ◽  
Vol 115 (30) ◽  
pp. E7081-E7090 ◽  
Author(s):  
Laura E. Bowie ◽  
Tamara Maiuri ◽  
Melanie Alpaugh ◽  
Michelle Gabriel ◽  
Nicolas Arbez ◽  
...  
Keyword(s):  
Dna Damage ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Oxidative Dna Damage ◽  
Model Systems ◽  
Protective Effects ◽  
Mutant Huntingtin ◽  
Naturally Occurring ◽  
Phosphate Donor ◽  
High Content Analysis

The huntingtin N17 domain is a modulator of mutant huntingtin toxicity and is hypophosphorylated in Huntington’s disease (HD). We conducted high-content analysis to find compounds that could restore N17 phosphorylation. One lead compound from this screen was N6-furfuryladenine (N6FFA). N6FFA was protective in HD model neurons, and N6FFA treatment of an HD mouse model corrects HD phenotypes and eliminates cortical mutant huntingtin inclusions. We show that N6FFA restores N17 phosphorylation levels by being salvaged to a triphosphate form by adenine phosphoribosyltransferase (APRT) and used as a phosphate donor by casein kinase 2 (CK2). N6FFA is a naturally occurring product of oxidative DNA damage. Phosphorylated huntingtin functionally redistributes and colocalizes with CK2, APRT, and N6FFA DNA adducts at sites of induced DNA damage. We present a model in which this natural product compound is salvaged to provide a triphosphate substrate to signal huntingtin phosphorylation via CK2 during low-ATP stress under conditions of DNA damage, with protective effects in HD model systems.

scholarly journals Brewer’s Spent Grains Protects against Oxidative DNA Damage in Saccharomyces cerevisiae

2017 ◽  
Vol 9 (7) ◽  
pp. 12
Author(s):  
Manuela M. Moreira ◽  
Daniel O. Carvalho ◽  
Rui Oliveira ◽  
Björn Johansson ◽  
Luís F. Guido
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Flow Cytometry ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Yeast Cells ◽  
Protective Effects ◽  
Genotoxic Effects ◽  
Barley Malt ◽  
Fold Reduction ◽  
Spent Grain

Brewer’s spent grain (BSG), obtained from barley malt during brewing, contains high amounts of phenolic acids, predominantly ferulic and p-coumaric acids. The protective effects of BSG extracts against oxidative DNA damage induced by H2O2 in Saccharomyces cerevisiae cells were investigated using an optimized yeast comet assay and flow cytometry. The results indicated that BSG extracts from black malt exhibited a 5-fold reduction in the genotoxic effects of H2O2, compared to the 2-fold decrease by the BSG extracts from pilsen malts. Flow cytometry analysis with dichlorofluorescein diacetate demonstrated that the intracellular oxidation of S. cerevisiae is also reduced to approximately 50% in the presence of 20-fold diluted BSG extracts. BSG extracts obtained from pilsen and black malt types exert dose-dependent protective properties against the genotoxic effects induced by ROS and decrease intracellular oxidation of yeast cells.

scholarly journals N-Acetyl Cysteine as a Novel Polymethyl Methacrylate Resin Component: Protection against Cell Apoptosis and Genotoxicity

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yu Zhang ◽  
Jian-feng Xiao ◽  
He-feng Yang ◽  
Yang Jiao ◽  
Wei-wei Cao ◽  
...  
Keyword(s):  
Dna Damage ◽  
Polymethyl Methacrylate ◽  
Cell Apoptosis ◽  
Oxidative Dna Damage ◽  
Redox Regulation ◽  
Protective Effects ◽  
Mitochondrial Apoptosis ◽  
Acetyl Cysteine ◽  
Pmma Resin

The present study investigated the antiapoptotic and antigenotoxic capabilities of N-acetyl cysteine- (NAC-) containing polymethyl methacrylate (PMMA) resin. An in vitro Transwell insert model was used to mimic the clinical provisional restorations placed on vital teeth. Various parameters associated with cell apoptosis and genotoxicity were investigated to obtain a deeper insight into the underlying mechanisms. The exposure of human dental pulp cell (hDPC) cultures to the PMMA resin (Unifast Trad™) resulted in a rapid increase in reactive oxygen species (ROS) level beginning at 1 h, which was followed by time-dependent cell detachment and overt death. The formation of γ-H2AX and cell cycle G1 phase arrest indicated that oxidative DNA damage occurred as a result of the interactions between DNA bases and ROS, beyond the capacities of cellular redox regulation. Such oxidative DNA damage triggers the activation of p53 via the ataxia telangiectasia mutated (ATM) signaling pathway and the induction of intrinsic mitochondrial apoptosis. Oxidative stress, cell apoptosis, and DNA damage induced by the PMMA resin were recovered to almost the level of untreated controls by the incorporation of NAC. The results indicate that the PMMA resin induced the intrinsic mitochondrial apoptosis as a consequence of p53 activation via the ATM pathway in response to oxidative DNA damage. More importantly, the incorporation of NAC as a novel component into the Unifast Trad™ PMMA resin offers protective effects against cell apoptosis and genotoxicity. This procedure represents a beneficial strategy for developing more biocompatible PMMA-based resin materials.

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