scholarly journals Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kenichi Kawahori ◽  
Yoshitaka Kondo ◽  
Xunmei Yuan ◽  
Yuki Kawasaki ◽  
Nozomi Hanzawa ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Methylation Status ◽  
Dna Demethylation ◽  
Fibroblast Growth Factor 21 ◽  
High Dose ◽  
Lactation Period ◽  
Dependent Manner ◽  
Suckling Period ◽  
Dna Hypermethylation ◽  
Rescue Dose

AbstractAscorbic acid (AA, vitamin C) serves as a cofactor for ten-eleven translocation (TET) enzymes and induces DNA demethylation in vitro. However, its role in DNA demethylation in vivo remains unclear. We previously reported that DNA demethylation in the mouse liver was enhanced during the suckling period. Therefore, we hypothesized that DNA demethylation is enhanced in an AA-dependent manner during the suckling period. To examine our hypothesis, we employed wild-type (WT) mice, which synthesize AA, and senescence marker protein-30/gluconolactonase (SMP30/GNL) knockout (KO) mice, which cannot synthesize AA, and analyzed the DNA methylation status in the livers of offspring in both the suckling period and adulthood. SMP30/GNL KO offspring showed DNA hypermethylation in the liver possibly due to low plasma and hepatic AA levels during the suckling period despite the administration of rescue-dose AA to dams. Furthermore, DNA hypermethylation of the fibroblast growth factor 21 gene (Fgf21), a PPARα target gene, persisted into adulthood. In contrast, a high-dose AA administration to SMP30/GNL KO dams during the lactation period restored DNA demethylation in the livers of offspring. Even though a slight increase was observed in plasma AA levels with the administration of rescue-dose AA to WT dams during the gestation and lactation periods, DNA demethylation in the livers of offspring was minimally enhanced. The present results demonstrate that AA intake during the suckling period is required for proper DNA demethylation in the liver.

scholarly journals Concentration-Dependent Antioxidant/Pro-Oxidant Activity of Ascorbic Acid in Chickens

2012 ◽  
Vol 66 (6) ◽  
pp. 256-260
Author(s):  
Nadežda Berzina ◽  
Jurijs Markovs ◽  
Mirdza Apsīte ◽  
Svetlana Vasiļjeva ◽  
Galina Smirnova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ascorbic Acid ◽  
Cadmium Concentration ◽  
Dehydroascorbic Acid ◽  
Cadmium Accumulation ◽  
Suppressive Effect ◽  
High Dose ◽  
Dependent Manner ◽  
Treatment Groups ◽  
Liver And Kidney

The effects of ascorbic acid supplementation on biomarkers of oxidative stress, cadmium accumulation in organs, immune system activity and kidney function in chickens were investigated. The treatment groups of chickens were fed either plain diet or diet supplemented with ascorbic acid at 100, 500, 1000 and 2000 mg/kg for four weeks. Liver and kidney tissues were assayed for cadmium concentration, and the hepatic levels of ascorbic acid and dehydroascorbic acid (DHAA; the oxidised form), malondialdehyde, glutathione, activity of glutathione peroxidase, blood serum uric acid, creatinine, lysozyme and circulating immune complexes were measured. Supplementation with a high dose of ascorbic acid (1000 and 2000 mg/kg in the diet) caused an imbalance between pro-oxidative and antioxidative activities, and induced a suppressive effect on innate immunity. The results suggest that oxidative stress compromises renal function. We observed that ascorbic acid increased cadmium accumulation in a dose-dependent manner.

scholarly journals Ascorbic acid attenuates activation and cytokine production in sepsis-like monocytes

2021 ◽  
Author(s):  
Tobias Schmidt ◽  
Robin Kahn ◽  
Fredrik Kahn
Keyword(s):  
Flow Cytometry ◽  
Ascorbic Acid ◽  
Cytokine Production ◽  
In Vitro Study ◽  
Surface Expression ◽  
High Dose ◽  
Functional Assay ◽  
Dependent Manner ◽  
Dose Dependent

Objective To investigate the effects of high dose ascorbic acid (AA) on monocyte polarization and cytokine production in vitro Design Experimental in vitro study of cells from healthy subjects and patients with sepsis Setting University research laboratory and academic hospital Subjects Six healthy controls and three patients with sepsis Interventions Monocytes were isolated from whole blood of healthy donors (n=6) and polarized in vitro for 48hrs using LPS or LTA. Polarization was confirmed by surface marker expression using flow cytometry. As a comparison, monocytes were also isolated from septic patients (n=3) and analyzed for polarization markers. The effect of AA on monocyte polarization was evaluated. As a functional assay, AA-treated monocytes were analyzed for cytokine production of TNF and IL-8 by intracellular staining and flow cytometry following activation with LPS or LTA. Measurements and Main Results Both LPS and LTA induced polarization in healthy monocytes in vitro, with increased expression of both pro- (CD40 and PDL1, p<0.05) and anti-inflammatory (CD16 and CD163, p<0.05) polarization markers, with non-significant effects on CD86 and CD206. This pattern resembled, at least partly, that of monocytes from septic patients. Treatment with AA significantly inhibited the upregulation of surface expression of CD16 and CD163 (p<0.05) in a dose dependent manner, but not CD40 or PDL-1. Finally, AA attenuated LPS or LTA-induced cytokine production of IL-8 and TNF in a dose-dependent manner (both p<0.05). Conclusions AA inhibits upregulation of anti-, but not pro-inflammatory related markers in LPS or LTA polarized monocytes. Additionally, AA attenuates cytokine production from in vitro polarized monocytes, displaying functional involvement. This study provides important insight into the immunological effects of high dose AA on monocytes, and potential implications in sepsis.

scholarly journals Author Correction: Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kenichi Kawahori ◽  
Yoshitaka Kondo ◽  
Xunmei Yuan ◽  
Yuki Kawasaki ◽  
Nozomi Hanzawa ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Dna Demethylation ◽  
Suckling Period

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Differential effects of two HDAC inhibitors with distinct concomitant DNA hypermethylation or hypomethylation in breast cancer cells

2019 ◽  
Author(s):  
Arunasree M. Kalle ◽  
Zhibin Wang
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Cells ◽  
X Chromosome ◽  
Breast Cancer Cells ◽  
Trichostatin A ◽  
Methylation Status ◽  
Dna Methyltransferases ◽  
Dependent Manner ◽  
Dna Hypermethylation

AbstractDNA methylation and histone acetylation are the two important epigenetic phenomena that control the status of X-chromosome inactivation (XCI), a process of dosage compensation in mammals resulting in active X chromosome (Xa) and inactive X chromosome (Xi) in females. While DNA methyltransferases (DNMTs) are known to maintain the DNA hypermethylation of Xi, it remains to be determined how one or a few of 18 known histone deacetylases (HDACs) contribute(s) to Xi maintenance. Herein we found that HDAC1/2/4/6 were overexpressed in breast cancer cells, MDA-MB-231, with Xa/Xa status compared to normal breast epithelial cells, MCF10A, with Xa/Xi status. Inhibition of these overexpressed HDACs with two different drugs, sodium butyrate (SB) and Trichostatin A (TSA), caused surprisingly distinct effects on global DNA methylation: hypermethylation and hypomethylation, respectively, as well as distinct effects on a repressing histone mark H3K27me3 for heterochromatin and an active mark H3K56ac for DNA damage. Surveying three DNMTs through immunoblot analyses for insights revealed the up- or down-regulation of DNMT3A upon drug treatments in a concentration-dependent manner. These results correlated with the decreased XIST and increased TSIX expression in MDA-MB 231 as a possible mechanism of Xi loss and were reversed with SB treatment. Further RNA-seq analysis indicated differential gene expression correlating with the promoter methylation status of a few genes. Collectively, our results demonstrate a crosstalk between HDACs and DNMTs and the novel involvement of HDACs in skewed Xi in breast cancer.

Abstract 198: Oxidative Stress Mediates the Augmented Muscle Mechanoreflex in Peripheral Arterial Disease Patients

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Matthew D Muller ◽  
Rachel C Drew ◽  
Cheryl A Blaha ◽  
Jessica L Mast ◽  
Jian Cui ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Peripheral Arterial Disease ◽  
Plantar Flexion ◽  
Limb Ischemia ◽  
Arterial Disease ◽  
High Dose ◽  
Dependent Manner ◽  
Low Intensity ◽  
Peripheral Arterial ◽  
Change In Mean

Background Exaggerated blood pressure (BP) responses to dynamic exercise predict cardiovascular mortality in peripheral arterial disease (PAD) patients. However, the underlying mechanisms are unclear and no attempt has been made to attenuate this response using antioxidants. Methods Three physiological studies were conducted in PAD patients and controls. In Protocol 1, subjects underwent four minutes of low-intensity (0.5-2.0 kg), rhythmic plantar flexion in the supine posture. In Protocol 2, PAD patients received high dose ascorbic acid intravenously prior to exercise. In Protocol 3, involuntary exercise was conducted via electrical stimulation of the tibial nerve. The primary outcome measure was the change in mean arterial pressure (ΔMAP) during the first 20 seconds of exercise (i.e. when mechanoreceptors within skeletal muscle activate the sympathetic nervous system). Results Compared to controls, PAD patients had significantly greater ΔMAP during plantar flexion, particularly at 0.5 kg of the most affected leg (11±2 vs. 2±1 mmHg) as well as the least affected leg (7±1 vs. 1±1 mmHg). This augmented response occurred before the onset of claudication pain and was attenuated by ∼50% (i.e. 6 mmHg) in the presence of ascorbic acid. Electrically evoked exercise also elicited larger hemodynamic changes in the PAD patients compared to controls. Further, the ΔMAP during 0.5 kg plantar flexion inversely correlated with the ankle-brachial index, indicating that patients with more severe resting limb ischemia had a larger BP response to exercise. Conclusions The BP response to low intensity exercise was enhanced in PAD. Chronic limb ischemia may sensitize muscle afferents and potentiate the autonomic response to muscle contraction in a dose-dependent manner.

PLASMA CORTICOSTEROID LEVELS AND ADRENAL ASCORBIC ACID AFTER INTRAVENOUS CORTICOTROPHIN INJECTIONS AND »STRESSFUL« STIMULI IN THE RAT

1962 ◽  
Vol 39 (4) ◽  
pp. 527-538 ◽  
Author(s):  
Pavo Hedner ◽  
Claus Rerup
Keyword(s):  
Ascorbic Acid ◽  
Abdominal Surgery ◽  
Response Curve ◽  
Significant Rise ◽  
Blocking Effect ◽  
High Dose ◽  
Ascorbic Acid Concentration ◽  
Unilateral Adrenalectomy ◽  
Subcutaneous Injections ◽  
Hypophysectomized Rats

ABSTRACT Measurements of plasma corticosteroid levels and adrenal ascorbic acid concentration in steroid blocked and hypophysectomized rats were performed. It was found that prednisolone and dexamethasone were effective in blocking endogenous corticotrophin release within 3–4 hours after subcutaneous injection. These agents also prevented completely the normally occurring rise in plasma corticoid levels after exposure of the rats to ether. Abdominal surgery (unilateral adrenalectomy) resulted in a slight but significant rise in plasma corticoid levels in spite of dexamethasone blockade. The values of adrenal ascorbic acid were not affected significantly. The blocking effect of two daily subcutaneous injections of a high dose of dexamethasone persisted for about one week after the last injection. The sensitivity of the plasma corticoid response was essentially the same in hypophysectomized and dexamethasone blocked rats. The lower part of the log dose response curve was found to be clearly non-linear in the plasma corticoid method following intravenous corticotrophin injection. As a consequence the dose level in quantitative assays of intravenously injected corticotrophin are, in our hands, of the same order as in the adrenal ascorbic acid depletion method.

scholarly journals High-dose Glycerol Monolaurate Up-Regulated Beneficial Indigenous Microbiota without Inducing Metabolic Dysfunction and Systemic Inflammation: New Insights into Its Antimicrobial Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1981 ◽  
Author(s):  
Qiufen Mo ◽  
Aikun Fu ◽  
Lingli Deng ◽  
Minjie Zhao ◽  
Yang Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Systemic Inflammation ◽  
Body Weight Gain ◽  
High Dose ◽  
Dependent Manner ◽  
Glucose And Lipid Metabolism ◽  
Glycerol Monolaurate ◽  
Indigenous Microbiota ◽  
Anti Inflammatory ◽  
Dose Dependent

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals A 65-Day Fumonisin B Exposure at High Dietary Levels Has Negligible Effects on the Testicular and Spermatological Parameters of Adult Rabbit Bucks

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 237
Author(s):  
András Szabó ◽  
Szabolcs Nagy ◽  
Omeralfaroug Ali ◽  
Zsolt Gerencsér ◽  
Miklós Mézes ◽  
...  
Keyword(s):  
Chromatin Condensation ◽  
Harmful Effect ◽  
Antioxidant Response ◽  
Membrane Lipid ◽  
Male Reproduction ◽  
Adult Rabbit ◽  
High Dose ◽  
Dependent Manner ◽  
Reproduction System ◽  
Testicular Weight

A 65-day study was undertaken to test the effects of two doses (10 and 20 mg/kg) of dietary fumonisin Bs (FB) on the rabbit male reproduction system. Body and testicular weight was not affected by the intoxication, neither the fatty acid composition of the testicular total phospholipids; the testis histological analysis failed to reveal any toxic effect. The FBs increased the testicular concentration and activity of reduced glutathione and glutathione peroxidase and decreased initial phase lipid peroxidation (conjugated dienes and trienes) in a dose dependent manner. Sperm morphology and chromatin condensation were monitored on Feulgen-stained smears. No significant differences were observed between the treatment groups and between sampling time points. The live cell ratio in the sperm (as assessed with flow cytometry) was not different among groups at any of the five sampling timepoints and was also identical within groups. Similarly, the spermatozoa membrane lipid profile was also identical in all three groups after the total intoxication period. In summary, it was demonstrated that FBs in an unrealistic and unjustified high dose still do not exert any drastic harmful effect on the leporine, male reproduction system, meanwhile slightly augmenting testicular antioxidant response.

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