Objective: Combination of thiazolidinediones and sulfonylureas as antidiabetic treatment is beneficial in terms of delaying the progression of type 2 diabetes that is the need for exogenous insulin therapy and insulin sensitizing effects. However, antidiabetic treatment is needed to be continued for longer period of time, it may interact with DNA & genetic material to produce genotoxic effects. In the present study, genotoxic potential of pioglitazone and glimepiride was evaluated at chromosomal, cellular and germinal level. Material and methods: Genotoxic potential of glimepiride & pioglitazone was evaluated by performing 4 weeks of genotoxicity study with the use of mammalian bone marrow chromosomal aberration assay, mammalian bone marrow erythrocyte assay and sperm abnormality assay. Three different doses of the pioglitazone & glimepiride combination as well as carboxymethylcellulose (0.5 %) as negative control and cyclophosphamide (40 mg/kg) as positive control groups were used in the study. Body weight was also measured to check systemic effects. Results and conclusion: The results revealed that pioglitazone and glimepiride combination produce significant structural chromosomal aberrations as well as sperm abnormalities moreover, the combination induce cytotoxicity only at higher dose. However, no significant changes were observed in numerical chromosomal aberrations in the form of micronucleus formation as well as in case of body weight. This controversial reports stress the need to evaluate the genotoxic potential of the combination after chronic treatment.
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