Investigation of genotoxic effects of piroxicam and tenoxicam, which are analgesic drug active substances

Analgesics are one of the most widely used groups of drugs in the world. Since the genotoxic and carcinogenic effects of some analgesic drugs have been identified, studies examining these effects have increased. In this study, the genotoxic effects of the analgesic drug active ingredients Tenoxicam and Piroxicam were examined by chromosomal aberration (CA) and micronucleus (MN) assays in human peripheral lymphocytes in vitro. In addition, mitotic index (MI) and nuclear division index (NDI) values were also determined. The results were examined by Z test. Regression analysis was performed with SPSS version 25.0 computer program to determine the concentration-effect relationship for application groups with significant variation compared to control concentrations. As a result, no significance was observed at any concentration of Piroxicam treatment compared to control in both 24- and 48-hour PA exposures. When the MN test was examined, the 48-hour exposure was 0,94 (p<0,01); concentrations of 1,88 (p<0,01) and 3,75 μg/mL (p<0,001) were significantly increased compared to the control (r=0,96). The mitotic index (MI) at concentrations of 1,88 and 3,75 μg/mL at 24 and 48 hours was significantly reduced compared to both the control (p<0,01, p<0,001) and solvent control (p<0,05, p<0,001, respectively). These decreases are not dependent on concentration (r=-0,14 for 24 hours, r=-0,24 for 48 hours). It was seen that the 24 hour treatment of Tenoxicam statistically increased at the highest concentration (10 μg/mL) (p<0.05) compared to the control (r=0,80). However, no toxic effects were observed in 48 hour CA treatment. The MN test concluded that 48-hour exposure did not produce a toxic effect at any concentration other than the highest concentration of 10 μg/mL (p<0,01) (r=0,95). Mitotic index (MI) showed significant decreases at concentrations of 1,25; 2,5; 5 and 10 μg/mL (p<0,05, p<0,01, p<0,01, p<0,001, respectively). These decreases are not dependent on concentration (r=-0,31 for 24 hours, r=-0,42 for 48 hours). Nuclear division index (NDI) results were unchanged for either active substance. As a result, it was found that both active substances can show genotoxic effects only at high concentrations. This work is pioneering for both Piroxicam and Tenoxicam, resulting from the lack of previous studies on human peripheral lymphocytes in vitro. These results need to be supported by different cell groups and in vivo tests.