In vitro evaluation of protective effect of telmisartan on arsenic-induced genotoxicity

Abstract

Background: Drinking of arsenic-contaminated water is one the most important ways of exposing human to this element, considering that as a substantial risk factor for the occurrence of various types of cancers and diseases. Carcinogenesis of arsenic has been attributed to its genetic toxicity and DNA damage through production of reactive oxygen free radicals. Telmisartan, as an antihypertensive drug, has antioxidant, anti-inflammatory, cytoprotective, and genoprotective properties. In this study, we studied the probable genoprotective effect of telmisartan on DNA damage caused by arsenic in human umbilical cord vein cells. Methods: At first, the human umbilical vein endothelial cells pretreated with different concentrations of telmisartan (0.01, 0.1, 1, and 10 µM) for 24 hours. Then, the cells incubated with 1 µM sodium meta arsenite (NaAsO 2 ) for 24 hours, and parameters of DNA damage were evaluated using comet assay method. The mixture of cells and agarose was put on slides, and after several steps of comet method, we stained them with ethidium bromide. The cells were examined under a fluorescent microscope. For each condition, 100 randomly selected cells on each slide could be scored, and DNA damage parameters were assessed. Findings: There was significant increase in tail length (22.33 ± 0.46 pixels), DNA in tail (24.5 ± 0.78 percent), and tail moment (5.59 ± 0.24 pixels percent) in arsenic-incubated cells compared to the control group (2.11 ± 0.19 pixels, 4.38 ± 0.48 percent, and 0.10 ± 0.01 pixels percent, respectively) (P < 0.001 for all). Significant decrease of above parameters of genotoxicity (2.46 ± 0.15 pixels, 9.51 ± 0.95 percent, and 0.33 ± 0.04 pixels percent, respectively) were observed after the pretreatment of cells with telmisartan (10 µM) for 24 hours as compared to the exposed cells with arsenic (P < 0.001 for all). Conclusion: Telmisartan reduces DNA damage caused by arsenic in vitro, and potentially can reduces the risk of cancer due to arsenic exposure.