Cytogenotoxic and Mutagenic Assessment of Sertraline in Vitro: Experimental Evidence and Molecular Docking Insights

İngilizce (OpenAlex)

ABSTRACT Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commonly used to treat depression, anxiety, and bipolar disorders. This study investigated the genotoxic, cytotoxic, and mutagenic effects of sertraline on human peripheral lymphocytes. Genotoxicity was assessed using chromosomal aberration (CA) and micronucleus (MN) assays, cytotoxicity by mitotic index (MI), nuclear division index (NDI), and abnormal cell percentage (ACP), and mutagenicity by the Ames test using Salmonella typhimurium TA98 and TA100 with and without S9 activation. Sertraline at 0.227, 0.455, 0.91, and 1.82 µg/mL caused no significant changes in ACP, CA/cell, or MI at 24 or 48 h. MN and binucleated micronucleated cell (BNMN) frequencies were unchanged at 24 h but increased at 48 h. NDI significantly decreased at all concentrations at 24h and at higher concentrations at 48 h. The Ames test showed no increase in revertant colonies. In silico analysis indicated a weak interaction between sertraline and DNA, with a binding energy of −5.12 kcal/mol. In conclusion, sertraline did not exhibit genotoxic or mutagenic effects in lymphocytes; however, the significant decrease in NDI, particularly at all concentrations after 24 h and at higher concentrations after 48 h, indicates a mild cytotoxic effect primarily associated with impaired cell proliferation.