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Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone
Karem Alzoubi1, Omar Khabour, Noor Hussain
1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan. khalzoubi@just.edu.jo
Abstract:
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.
Insights
Pioglitazone, used for type 2 diabetes, causes DNA damage and chromosomal aberrations in human cells. Vitamin B12 pretreatment effectively protected against this genotoxic effect, suggesting a potential protective strategy.
Area of Science:
- Genotoxicology
- Molecular Biology
- Pharmacology
Background:
- Pioglitazone is a thiazolidinedione antidiabetic drug.
- Previous research indicates pioglitazone may induce DNA damage via oxidative stress.
Purpose of the Study:
- To investigate the mutagenic and genotoxic effects of pioglitazone on human lymphocytes.
- To evaluate the protective role of vitamin B12 against pioglitazone-induced DNA damage.
Main Methods:
- Sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) assays were performed on cultured human lymphocytes.
- Oxidative DNA damage was assessed by measuring 8-hydroxy-2'-deoxyguanosine (8-OH-dG).
- Vitamin B12 was used as a potential protective agent.
Main Results:
- Pioglitazone treatment significantly increased the frequency of SCEs and CAs (p<0.01).
- A significant elevation in 8-OH-dG levels was observed after pioglitazone exposure (p<0.01).
- Vitamin B12 pretreatment mitigated the genotoxic effects of pioglitazone.
Conclusions:
- Pioglitazone exhibits genotoxic properties, inducing chromosomal and oxidative DNA damage in human lymphocytes.
- Vitamin B12 demonstrates a protective effect against pioglitazone-induced genotoxicity.
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