Alterations of GSH and MDA levels and their association with bee venom-induced DNA damage in human peripheral blood leukocytes.
Bee venom (BV) has toxic effects in a variety of cell systems and oxidative stress has been proposed as a possible mechanism of its toxicity. This study investigated the in vitro effect of BV on glutathione (GSH) and malondialdehyde (MDA) levels, and their association with BV-induced DNA strand breaks and oxidative DNA damage in human peripheral blood leukocytes (HPBLs). Blood samples were treated with BV at concentrations ranging from 0.1 to 10 μg/ml over different lengths of time, and DNA damage in HPBLs was monitored with the alkaline and formamidopyrimidine glycoslyase (FPG)-modified comet assays, while GSH and MDA levels were determined in whole blood. Results showed a significant increase in overall DNA damage and FPG-sensitive sites in DNA of HPBLs exposed to BV compared with HPBLs from controls. An increase in DNA damage (assessed with both comet assays) was significantly associated with changes in MDA and GSH levels. When pretreated with N-acetyl-L-cysteine, a source of cysteine for the synthesis of the endogenous antioxidant GSH, a significant reduction of the DNA damaging effects of BV in HPBLs was noted. This suggests that oxidative stress is at least partly responsible for the DNA damaging effects of BV.
Mutagenesis Unit, Institute for Medical Research and Occupational Health, Zagreb, Croatia. ggajski@imi.hr
Goran
G
Gajski
Ana-Marija
AM
Domijan
Vera
V
Garaj-Vrhovac
D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D001514:Bee Venoms / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000097:blood*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects
D001514:Bee Venoms; D016166:Free Radical Scavengers; D008315:Malondialdehyde; D043382:DNA-Formamidopyrimidine Glycosylase; D005978:Glutathione; D000111:Acetylcysteine