Assessment of the genotoxic effects of antihypertensive drug active ingredient indapamide in human lymphocytes

Abstract

Hypertension is the most common cardiovascular disease and is also known as high blood pressure. The large majority of hypertensive patients need long-term administration of antihypertensive agents. Indapamide is an orally administered diuretic antihypertensive drug. The present work aimed to assess the possible genotoxic effects of indapamide using four different assays: chromosomal aberration (CA), sister chromatid exchange (SCE), micronucleus (MN), and comet. Lymphocytes from three different donors were exposed to 18.75, 37.50, 75.00, and 100.00 μg/ml indapamide. Additionally, a negative, a positive (mitomycin C = MMC, 0.20 μg/ml), and a solvent control (5.4 μl/ml methanol) were also applied. As a result, it was seen that indapamide did not cause a significant change in CAs and MN frequencies compared to the control. It caused significant damage only at the highest concentration in the comet assay. Similarly, while it did not affect the number of SCEs in the 24-h treatment, it increased the SCE frequency at the two highest concentrations in the 48-h. Mitotic index (MI) decreased at almost all concentrations. Considering all these results, this study revealed that indapamide did not have a significant genotoxic effect in these conditions. To the best of our knowledge, this is the first investigation about the genotoxic effect of indapamide in human lymphocytes in vitro.