Radioprotective effect of dl-α-lipoic acid on mice skin fibroblasts
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During the course of cancer radiation treatment, normal skin invariably suffers from the cytotoxic effects of γ-radiation and reactive oxygen species (ROS), which are generated from the interaction between radiation and the water molecules in cells. The present study was designed to investigate the radioprotective role of α-lipoic acid (LA), an antioxidant on murine skin fibroblasts exposed to a single dose of 2, 4, 6, or 8Gy γ-radiation. Irradiation of fibroblasts significantly increased ROS, nitric oxide, and lipid peroxidation (P < 0.001); all of these factors substantially decreased with 100 μM LA treatment. Hydroxyl radical (OH⋅) production from 8Gy irradiated fibroblasts was measured directly by electron spin resonance using spin-trapping techniques. LA was found to inhibit OH⋅ production at 100-μM concentrations. Dose-dependent depletion of antioxidants, such as catalase and glutathione reductase, was observed in irradiated fibroblasts (P < 0.001), along with increased superoxide dismutase (P < 0.001). LA treatment restored antioxidant levels. Concentration of the pro-inflammatory cytokine IL-1β was significantly reduced in irradiated fibroblasts when treated with LA. MTT and lactate dehydrogenase assays demonstrated that LA treatment reduced cell injury and protected cells against irradiation-induced cytotoxicity. Thus, we conclude that results are encouraging and need further experiments to demonstrate a possible benefit in cancer patients and the reduction of harmful effects of radiation therapy.
Keywordsγ-Radiation α-Lipoic acid Radioprotection Antioxidant Fibroblasts Reactive oxygen species
We thank Dr. R.R. Rai, Dr. Rai Memorial Medical Centre for providing the necessary irradiation facilities and help in radiation dosimetry. The authors Dr. J.G.M and Dr. E.P.J. thank the Council of Scientific and Industrial Research (CSIR, New Delhi), India for awarding a fellowship. Dr. V.A. thanks the Indian Council of Medical Research, New Delhi, India for awarding senior research fellowship. Finally, we thank the reviewers for their valuable comments and suggestion.
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