Role of folic acid in nitric oxide bioavailability and vascular endothelial function

Stanhewicz, Anna E.; Kenney, W. Larry

doi:10.1093/nutrit/nuw053

Cited by 119 publications

(93 citation statements)

References 124 publications

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“…Folic acid,a member of the B-vitamin family, is essential for amino acid metabolism. Adequate intake of folic acid is vital for metabolism, cellular homeostasis, and DNA synthesis [25] . In our study, we observed that many cardiotoxic effect induced by methotrexate could partially reversed by the use of folic acid both at light and electron microscope level also both necrosis and apoptosis were less compared to the group treated with methtrexate.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, folic acid supplementation is essential for development of the heart and its deficiency led to ventricular septal defects [27] . Many physiological studies were done to study the benefits of folic acid and reported that folic acid supplementation could reverse endothelial dysfunction in patients with cardiovascular disease [25] . The mechanism of folic acid in protection of endothelial cells suggest that folic acid and its active metabolite 5-methyl tetrahydrofolate improve nitric oxide bioavailability by increasing endothelial nitric oxide synthase coupling and nitric oxide production as well by scavenging superoxide radicals and so improve endothelial function, thereby preventing or reversing the progression of cardiovascular diseases [25] .…”

Section: Discussionmentioning

confidence: 99%

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Histological and immunohistochemical study of the possible protective effect of folic acid on the methotrexate- induced cardiac muscle toxicity in male albino rats

Mohamed

Nor-Eldin

2018

Egyptian Journal of Histology

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Introduction: Methotrexate is widely used as a chemotherapeutic agent in cancers, ectopic pregnancies and rheumatic arthritis. Folic acid is found in dark green leafy vegetables. Methotrexate is folic acid antagonist that prevents its conversion to tetrahydro folic acid. Aim: This research aimed to study the protective effect of folic acid on the histological changes produced by methotrexate in cardiac muscles. Materials and Methods: Thirty adult male albino rats were divided into three equal groups. Group I (control group) 10 rats injected intraperitoneally with saline. Group II rats were intraperitoneally injected with methotrexate at a dose of 5mg/kg/day for one month. Group III: were intraperitoneally injected with methotrexate at a dose of (5mg/kg/day) with concomitant oral folic acid at a dose of (0.1mg/kg/day) for one month. After 24 hrs of the last dose, the animals were dissected. Hearts were processed for haematoxyline and eosine stain, immunohistochemical stains and electron microscopic examination. Results: Both degenerative and apoptotic changes were observed in the cardiac muscles in the methotrexte-treated group, these changes were attenuated by administration of folic acid. Conclusion: Folic acid is beneficial to the cardiac muscles during methotrexate treatment and should be used concomitant with methotrexate treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Histological and immunohistochemical study of the possible protective effect of folic acid on the methotrexate- induced cardiac muscle toxicity in male albino rats

Mohamed

Nor-Eldin

2018

Egyptian Journal of Histology

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“…Guo et al15 found that FA therapy could significantly improve endothelial function. Most studies of the relationship between FA and atherosclerosis have focused on FA's ability to reduce serum homocysteine levels 24 or on FA's antioxidant,7 anti‐inflammatory11 and antithrombotic effects 14. Little is known regarding the regulatory effects of FA on VSMC dedifferentiation, which is necessary for the development and progression of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Folic acid delays development of atherosclerosis in low‐density lipoprotein receptor‐deficient mice

Pan

Liu

Gao

et al. 2018

J Cellular Molecular Medi

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Many studies support the cardioprotective effects of folic acid (FA). We aimed to evaluate the utility of FA supplementation in preventing the development of atherosclerotic in low‐density lipoprotein receptor‐deficient (LDLR−/−) mice and to elucidate the molecular processes underlying this effect. LDLR−/− mice were randomly distributed into four groups: control group, HF group, HF + FA group and the HF + RAPA group. vascular smooth muscle cells (VSMCs) were divided into the following four groups: control group, PDGF group, PDGF + FA group and PDGF + FA + RAPA group. Blood lipid levels, oxidative stress and inflammatory cytokines were measured. Atherosclerosis severity was evaluated with oil red O staining. Haematoxylin and eosin (H&E) staining was used to assess atherosclerosis progression. Immunohistochemical staining was performed with antismooth muscle α‐actin (α‐SMA) antibodies and anti‐osteopontin (OPN) antibodies that demonstrate VSMC dedifferentiation. The protein expression of α‐SMA, OPN and mechanistic target of rapamycin (mTOR)/p70S6K signalling was detected by Western blot analysis. FA and rapamycin reduced serum levels of total cholesterol, triacylglycerol, LDL, inhibiting oxidative stress and the inflammatory response. Oil red O and H&E staining demonstrated that FA and rapamycin inhibited atherosclerosis. FA and rapamycin treatment inhibited VSMC dedifferentiation in vitro and in vivo, and FA and rapamycin attenuated the mTOR/p70S6K signalling pathway. Our findings suggest that FA attenuates atherosclerosis development and inhibits VSMC dedifferentiation in high‐fat‐fed LDLR−/− mice by reduced lipid levels and inhibiting oxidative stress and the inflammatory response through mTOR/p70S6K signalling pathway.

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“…31- 35 The importance to CVD has primarily been investigated due to the role of FA in lowering Hcy, and also due to its ability to enhance nitric oxide production, thereby reducing the endothelial dysfunction associated with CVD. 36, 37 Similarly, folate plays a role in the recycling of tetrahydrobiopterin, a cofactor involved in the synthesis of the neurotransmitters dopamine, serotonin and noradrenaline. 32,34…”

Section: Roles Of Folate In Healthmentioning

confidence: 99%

Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

Barnett¹,

D’Cunha

Georgousopoulou

et al. 2017

Exploratory Research and Hypothesis in Medicine

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Folate has been proposed to be an efficacious treatment strategy for depression. The mandatory fortification of flour with synthetic folic acid (FA) in over 80 countries has yielded improvements in folate intake; however, depression is still a considerable public health concern. While there are established benefits of FA fortification in reducing risk of neural tube defects, the implications regarding depression are unclear, especially in individuals with certain genetic polymorphisms. Therefore, a systematic review was conducted to examine the effects of folate to treat depression. Following PRISMA guidelines, a systematic review was conducted of electronic databases (PUBMED, Scopus, CINAHL, and Cochrane Library) to identify human clinical trials examining the effects of folate (including FA) supplementation in the management or prevention of depression, the impact on inflammatory markers and if genetic polymorphisms were considered. Ten trials met the inclusion criteria. Seven trials examined effects of either adjunctive FA or L-methylfolate (L-MTHF) supplementation with antidepressants in the management of depression and three examined effects of FA supplementation alone for prevention of depression. No benefit of FA was found compared to placebo (all, p > 0.05). The single L-MTHF trial that explored the interplay of genetic polymorphisms and methylation status found benefit in the Hamilton depression rating scale from adjunctive treatment with 15 mg/day of L-MTHF compared with placebo (−6.8 ± 7.2 vs. −3.7 ± 6.5; p = 0.017) and improvement with L-MTHF for most genetic markers. Currently, there is no evidence to support FA supplementation for the management or prevention of depression. More research is required to determine the efficacy of L-MTHF and folinic acid in certain clinical populations.

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Role of folic acid in nitric oxide bioavailability and vascular endothelial function

Cited by 119 publications

References 124 publications

Histological and immunohistochemical study of the possible protective effect of folic acid on the methotrexate- induced cardiac muscle toxicity in male albino rats

Histological and immunohistochemical study of the possible protective effect of folic acid on the methotrexate- induced cardiac muscle toxicity in male albino rats

Folic acid delays development of atherosclerosis in low‐density lipoprotein receptor‐deficient mice

Effect of Folate Supplementation on Inflammatory Markers in Individuals Susceptible to Depression: A Systematic Review

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