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    Vitamin D3, L‑Arginine, L‑Citrulline, and Antioxidant Supplementation Enhances Nitric Oxide Bioavailability and Reduces Oxidative Stress in the Vascular Endothelium – Clinical Implications for Cardiovascular System

    Hazem Dawoud1, Tadeusz Malinski1★★ Corresponding author

    1. 1Department of Chemistry and Biochemistry, Nanomedical Research Laboratories, Ohio University, Athens, Ohio, USA.

    CORRESPONDENCE

    Tadeusz Malinski

    Department of Chemistry and Biochemistry, Nanomedical Research Laboratories, Ohio University, Athens, Ohio, USA.

    malinski@ohio.edu

    Volume 12, Issue 1 · pp. 17–23 · PUBLISHED · DOI: 10.4103/pr.pr_79_19

    View on Pharmacogn. Res. original site ↗

    ABSTRACT

    Background: Nitric oxide (NO) is a crucial signaling molecule which regulates the blood flow and prevents the adhesion of blood components to the vascular wall. A deficiency in bioavailable NO concentration is associated with the dysfunction of endothelial NO synthase (eNOS) and/or an increase in oxidative stress. The deficiency of bioavailable NO is a common denominator of several cardiovascular diseases, including diabetes, atherosclerosis, and hypertension.Materials and Methods: We used a nanomedical technology to elucidate the balance between bioavailable NO and oxidative stress (peroxynitrite ONOO−) in human umbilical vein endothelial cells (HUVECs) treated with a supplement containing L‑arginine, L‑citrulline, Vitamin D3, and antioxidants. Nanosensors, with a diameter of 200–300 nm, are capable of measuring in situ NO and peroxynitrite (ONOO−) concentrations produced by single endothelial cells. Results: The ratio of the concentration of cytoprotective NO [NO] to the concentration of cytotoxic peroxynitrite [ONOO−] was used to estimate the efficiency of eNOS. HUVECs incubated with L‑citrulline, L‑arginine, and Vitamin D3 increased the [NO]/[ONOO−] ratio by 25%, while in the presence of antioxidants, the increase was 15%. The synergistic effect between the mix of L‑arginine, L‑citrulline, Vitamin D3, and antioxidants was a favorable increase of the overall [NO]/[ONOO−] ratio by 50%. Conclusion: The findings of the study presented here clearly indicate that L‑arginine, L‑citrulline, and Vitamin D3 can significantly alter the function of the endothelium and NO production, in a favorable manner, while pointedly reducing ONOO− – the main component of oxidative stress. This effect can be significantly potentiated in the presence of antioxidants.

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      Dawoud, H., & Malinski, T. (). Vitamin D3, L‑Arginine, L‑Citrulline, and Antioxidant Supplementation Enhances Nitric Oxide Bioavailability and Reduces Oxidative Stress in the Vascular Endothelium – Clinical Implications for Cardiovascular System. Pharmacognosy Research, 12(1), 17–23. https://doi.org/10.4103/pr.pr_79_19