Cytoprotection against Cr(6+)-induced DNA damage by alpha-lipoic acid: implications in reducing occupational cancer risk.
Alpha-lipoic acid (LA), the metabolic antioxidant, was evaluated for its potential to protect against Cr(6+)-induced DNA damage. Potassium dichromate was administered to Swiss albino mice orally ad libitum at the doses of 5, 10 or 25 mg/kg body weight in drinking water to set DNA damage in cells, which was characterized in mouse peripheral blood mononuclear cells and bone marrow cells using single-cell gel electrophoresis and analyses of generated comets for Tail moment, Tail DNA and Tail length. DNA damage was dose dependent. Cytoprotection by LA was remarkable. LA (5, 10 and 25 mg/kg body weight intraperitoneally) in pre-, co- and post-toxicant administration schedule abrogated DNA damage substantially in both cell types. Protection by LA was also dose dependent. LA annulled DNA damage by Cr(6+) in plasmid relaxation assay. A negligible DNA damage resulted during interaction of Cr(6+) and LA. Compared to ascorbate, LA emerged as a better antioxidant and least DNA damaging. In conclusion, our study advocated an experimental therapeutic research potential in LA against Cr(6+)-induced DNA damage for reduction of occupational cancer risk in humans.
Kumar
Sushil
S
Environmental Carcinogenesis Laboratory, Indian Institute of Toxicology Research (CSIR), Mahatma Gandhi Marg, PO Box 80, Lucknow-226001, India. sushilkumar@iitr.res.in
Budhwar
Roli
R
Nigam
Akanksha
A
Priya
Shivam
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D002857:Chromium / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D051379:Mice; D008957:Models, Genetic; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics*; D016273:Occupational Exposure; D018384:Oxidative Stress; D011192:Potassium Dichromate / Q000633:toxicity; D013696:Temperature; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D002857:Chromium; C074702:chromium hexavalent ion; D008063:Thioctic Acid; D011192:Potassium Dichromate