Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone.
Pioglitazone is a prototype of thiazolidinediones, used for the treatment of type 2 diabetes mellitus. Previous studies suggest that pioglitazone might cause DNA damage by generation of oxidative species. In this study, we investigated the mutagenic effects of pioglitazone using sister chromatid exchanges (SCEs), and chromosomal aberrations (CAs) assays in cultured human lymphocytes. In addition, oxidative DNA damage was evaluated in cells culture by measuring 8-hydroxy-2'-deoxyguanosine (8-OH-dG) marker. We also investigated the possible protective effects of vitamin B12, which is associated with DNA repair, on DNA damage induced by pioglitazone. Treatment of the human lymphocytes with pioglitazone (100μM) significantly increases the frequency of SCEs and CAs (p<0.01). In addition, significant elevation in 8-OH-dG release from lymphocytes was observed after treatment with pioglitazone (p<0.01). On the other hand, pretreatment of cultures with vitamin B12 (13.5μg/ml) protected lymphocytes from the genotoxic effect of pioglitazone. Therefore, we conclude that pioglitazone is genotoxic, and it induces chromosomal and oxidative DNA damage in cultured lymphocytes and this toxicity is prevented by pretreatment with vitamin B12.
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan. khalzoubi@just.edu.jo
Karem
K
Alzoubi
Omar
O
Khabour
Noor
N
Hussain
Sayer
S
Al-Azzam
Nizar
N
Mhaidat
D000328:Adult; D016587:Antimutagenic Agents / Q000494:pharmacology*; D002869:Chromosome Aberrations; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000633:toxicity*; D008297:Male; D000077205:Pioglitazone; D012854:Sister Chromatid Exchange; D045162:Thiazolidinediones / Q000633:toxicity*; D014805:Vitamin B 12 / Q000494:pharmacology*; D055815:Young Adult
D016587:Antimutagenic Agents; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014805:Vitamin B 12; D000077205:Pioglitazone