Possible genotoxic effects of antihypertensive drug active ingredients Amlodipine and Ramipril

Abstract

Antihypertensive drugs are used to keep high blood pressure within a certain range and in balance. Long-term use of antihypertensives may be required for therapeutic purposes. Amlodipine, which is the active ingredient of antihypertensive drugs, acts as a calcium channel blocker, and Ramipril acts as an angiotensin converting enzyme (ACE) inhibitor. In this study, in vitro genotoxic e ff ects of Amlodipine and Ramipril were determined in human peripheral blood lymphocytes. Chromosomal aberrations (CAs) and micronucleus (MN) assays were examined using concentrations of 0.39, 0.78, 1.56, 3.13, 6.25 mu g mL-1 for Amlodipine and 19.53, 39.06, 78.13, 156.25, 312.50 mu g mL-1 for Ramipril. The e ff ects of these active ingredients on mitotic index (MI) and nuclear division index (NDI) were also investigated. As a result, Amlodipine did not cause a significant change in CA frequency compared to the control and solvent control at both 24 and 48-h treatment periods. Ramipril increased CAs at the three highest concentrations (78.13, 156.25 and 312.50 mu g mL-1 ) only at 48-h. Both active ingredients decreased MI at high concentrations at all treatment times. Amlodipine did not cause a significant di ff erence in MN and NDI values compared to control and solvent control. Besides, Ramipril treatment caused an increase in MN frequency again at high concentrations. In addition, it was determined that it had no e ff ect on NDI. It was concluded that Amlodipine may not cause genotoxic e ff ects in human lymphocytes in vitro , while Ramipril may be genotoxic only at high concentrations.