Investigation of the genotoxic effects of antihypertensive drug actual ingredients amlodipinee and Ramipril

Antihypertensive drugs are used to keep high blood pressure within a certain range and in balance. Long-term or even lifetime 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 effects of Amlodipine and Ramipril were determined in human peripheral blood lymphocytes using chromosomal abnormalities (CA) and micronucleus test (MN). In addition, the effects of these drug active ingredients on the mitotic index (MI) and nuclear division index (NDI) were also investigated. 0.36 for Amlodipine; 0.78; 1.56; 3.13; 6.25 µg/mL, 19.53 for Ramipril; 39.6; 78.3; 156.2; Concentrations of 312.5 µg/mL were used. As a result of the examinations, it is seen that both the 24 and 48 hour treatment periods of Amlodipine did not cause a significant change in the frequency of chromosomal abnormalities compared to the control and solvent control. According to the results of the chromosomal abnormality test of Ramipril, another antihypertensive drug active ingredient, the percentage of abnormal cells in the 24-hour application did not show a significant change compared to the control and solvent control. However, in the 48-hour application, an increase was observed in the percentage of abnormal cells and the number of abnormalities per cell at the three highest concentrations (78.13; 156.25 and 312.5 µg/mL). It was determined that Amlodipine caused a significant decrease in the mitotic index values at the two highest concentrations (3.13 and 6.25 μg/mL) compared to the control and solvent control in both treatment periods. The mitotic index values of ramipril were 39.6; 78.3; 156.2 and 312.5; A significant decrease in μg/mL concentrations compared to the control and 78.3; 156.2 and 312.5; At μg/mL concentrations, a significant decrease is observed compared to the solvent control. Amlodipine did not cause a significant difference in micronucleus and nuclear division index values compared to control and solvent control. On the other hand, it was observed that Ramipril application caused an increase in micronucleus frequency compared to control and solvent control. While this increase was statistically significant at all concentrations except the lowest concentration compared to the control, it was significant at the three highest concentrations (78.53; 156.25 and 312.5 µg/ml) compared to the solvent control. As a result of the study, it was determined that Ramipril did not have any effect on the nuclear division index. As a result, it was concluded that Amlodipine and Ramipril may have a significant cytotoxic effect at high concentrations in human lymphocytes in vitro, whereas Amlodipine may not cause a genotoxic effect, while Rampril may be genotoxic especially at high concentrations.