Radioprotective effect of DL-alpha-lipoic acid on mice skin fibroblasts.
During the course of cancer radiation treatment, normal skin invariably suffers from the cytotoxic effects of gamma-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 alpha-lipoic acid (LA), an antioxidant on murine skin fibroblasts exposed to a single dose of 2, 4, 6, or 8Gy gamma-radiation. Irradiation of fibroblasts significantly increased ROS, nitric oxide, and lipid peroxidation (P < 0.001); all of these factors substantially decreased with 100 microM 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-microM 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-1beta 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.
Department of Bioinformatics, Sri Ramachandra University, Chennai 600116, India.
G Dicky John
GD
Davis
J Gunasingh
JG
Masilamoni
V
V
Arul
M Siva Muthu
MS
Kumar
U
U
Baraneedharan
Solomon F D
SF
Paul
I Vignesh
IV
Sakthivelu
E Philip
EP
Jesudason
R
R
Jayakumar
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D005980:Glutathione Reductase / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D053583:Interleukin-1beta; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D008063:Thioctic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase