title: 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.
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.
authors.affiliation: Department of Pharmacology, The Nippon Dental University, School of Life Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo, 102-8159, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.forename: Takeki
authors.initials: T
authors.lastname: Tsutsui
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miwa
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005978:Glutathione / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000528:radiation effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects* / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014965:X-Rays
chemical_list: D000975:Antioxidants; C468783:H2AX protein, human; D006657:Histones; D010168:Palmitates; D017382:Reactive Oxygen Species; D005978:Glutathione; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid