Assessment of the genotoxicity and cytotoxicity of etazolate in cultured human lymphocytes

Abstract

Etazolate is a pyrazolopyridine compound that exhibits a range of pharmacological mechanisms, including inhibition of phosphodiesterase-4 activity and modulation of the γ-aminobutyric acid (GABA) signaling pathway. Etazolate has shown promising results in treating depression, traumatic brain injury, and Alzheimer's disease in animal models and clinical trials. However, limited information is available regarding its genotoxicity and cytotoxicity to human cells. Therefore, the current study aims at testing the effect of etazolate on the genetic material using two genotoxicity assays. In addition, the study aims to evaluate the effect of etazolate on the mitotic index (MI) of cultured human lymphocytes. Different concentrations of etazolate (0.01, 1, 10, and 50 µM) were used. Genotoxicity was assessed using the chromosomal aberrations (CAs) assay, and oxidative DNA damage was assessed using the 8-hydroxy-2deoxyguanosine (8-OHdG) assay, while cytotoxicity was assessed using the MI assay. Treatment of cultured human lymphocytes with etazolate did not induce CAs at all concentrations examined (p > 0.05). In addition, the normal level of 8-OHdG detected in the control group was not affected by etazolate treatment (p > 0.05). Furthermore, no effect was observed for etazolate on the MI (p > 0.05). In conclusion, current results indicate that etazolate is neither genotoxic nor cytotoxic to cultured human lymphocytes using the indicated assays at the examined concentrations.