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The lipophilic vitamin C derivative, 6-o-palmitoylascorbate, protects human lymphocytes, preferentially over ascorbate, against X-ray-induced DNA damage, lipid peroxidation, and protein carbonylation

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Abstract

The aim of this study was to investigate protective effects of the lipophilic vitamin C derivative, 6-o-palmitoylascorbate (PlmtVC), against X-ray radiation-induced damages including cell death, DNA double-strand breaks (DSBs), lipid peroxidation, and protein carbonylation in human lymphocytes HEV0082, and the stability of PlmtVC under cell-cultured or cell-free condition. Irradiation with X-ray (1.5 Gy) diminished the cell viability and induced apoptosis, both of which were protected by pre-irradiational administration with PlmtVC. Gamma-H2A.X foci as a hallmark of DSBs were markedly enhanced in the irradiated cells. PlmtVC prevented X-ray-induced DSBs more appreciably than l-ascorbic acid (l-AA). Intracellular ROS production, lipid peroxidation, and protein carbonylation in HEV0082 cells were increased by X-ray at 1.5 Gy, all of which were significantly repressed by PlmtVC. PlmtVC also elevated endogenous reduced glutathione (GSH) in HEV0082 cells, and prevented X-ray-induced GSH depletion that are more appreciably over l-AA. Thus, PlmtVC prevents X-ray-induced cell death through its antioxidative activity. Stability tests showed that after being kept under physiological conditions (pH 7.4, 37 °C) for 14 days, vitamin C residual rates in PlmtVC solutions (62.2–82.0 %) were significantly higher than those in l-AA solutions (20.5–28.7 %). When PlmtVC or l-AA was added to HEV0082 lymphocytes, intracellular vitamin C in l-AA-treated cells was not detectable after 24 h, whereas PlmtVC-treated cells could keep a high level of intracellular vitamin C, suggesting an excellent stability of PlmtVC. Thus, X-ray-induced diverse harmful effects could be prevented by PlmtVC, which was suggested to ensue intrinsically from the persistent enrichment of intracellular vitamin C, resulting in relief to X-ray-caused oxidative stress.

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Authors and Affiliations

  1. Department of Pharmacology, The Nippon Dental University, School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan

    Li Xiao & Takeki Tsutsui

  2. Department of Radiological Technology, Faculty of Health Sciences, Butsuryo College of Osaka, Otorikitamachi 3-33, Nishi-ku, Sakai, Osaka, 593-8328, Japan

    Nobuhiko Miwa

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  1. Li Xiao
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Correspondence to Nobuhiko Miwa.

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Xiao, L., Tsutsui, T. & Miwa, N. The lipophilic vitamin C derivative, 6-o-palmitoylascorbate, protects human lymphocytes, preferentially over ascorbate, against X-ray-induced DNA damage, lipid peroxidation, and protein carbonylation. Mol Cell Biochem 394, 247–259 (2014). https://doi.org/10.1007/s11010-014-2101-8

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