Protective effect of deferoxamine on chromium (VI)-induced DNA single-strand breaks, cytotoxicity, and lipid peroxidation in primary cultures of rat hepatocytes.
Incubation of primary cultures of rat hepatocytes with K2CR2O7 and deferoxamine (DFO), an iron chelator, resulted in a marked decrease in cellular levels of DNA single-strand breaks caused by K2Cr2O7. Cellular treatment with DFO also suppressed both dichromate-induced cytotoxicity--evaluated by the leakage of lactate dehydrogenase, and lipid peroxidation--as monitored by malondialdehyde formation. In addition, treatment with DFO attenuated the suppression of the levels of vitamin E and C as well as the inhibition of alkaline phosphatase and glutathione peroxidase activity attributed to K2Cr2O7. However, DFO had no influence on the cellular level of glutathione or the activity of glutathione reductase and superoxide dismutase suppressed by dichromate. Under the same experimental conditions, cellular uptake and distribution of chromium were not affected by DFO. These results indicate that DFO protects cells from chromium (VI)-induced DNA strand breaks, cytotoxicity, lipid peroxidation, vitamin E and C depression, and glutathione peroxidase inhibition The role of antioxidants in chromium (VI)-induced cytotoxicity, DNA breaks, and lipid peroxidation is discussed.
Susa
N
N
Department of Veterinary Public Health, School of Veterinary Medicine and Animals Sciences, Kitasato University, Aomori Japan.
Ueno
S
S
Furukawa
Y
Y
Sugiyama
M
M
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D002424:Caustics / Q000378:metabolism / Q000633:toxicity; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects* / Q000235:genetics; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011192:Potassium Dichromate / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D000931:Antidotes; D002424:Caustics; D004277:DNA, Single-Stranded; D014810:Vitamin E; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D000469:Alkaline Phosphatase; D005978:Glutathione; D003676:Deferoxamine; D001205:Ascorbic Acid; D011192:Potassium Dichromate