In vitro cytogenotoxic effects of hydroxychloroquine sulfate compound

This study was carried out to investigate the cytogenotoxic effects of the 4-amino quinoline group hydroxychloroquine sulfate (hydroxychloroquine sulfate) (HCQ) compound, which has both antimalarial and immunomodulatory effects. Studies were performed in vitro conditions with healthy human lymphocytes and bacterial strains. For the Ames reversion test, Salmonella typhimurium mutant auxotrophic TA98 and TA100 strains were exposed to HCQ concentrations of 5, 10, 20, 40, and 80 µg/petri for 72 hours. Here, HCQ did not show a mutagenic effect in the TA98 strain but caused a decrease in the number of colonies in the TA100 strain. According to the comet test data on lymphocytes, the test substance did not significantly affect the Genetic Damage Index (GHI) and Damaged Cell Ratio (HHO). According to the DNA damaging-protective activity test findings, HCQ did not show a significant damaging effect on pBR322 plasmid DNA alone; on the contrary, it showed signs of a possible protective (antiradical) potential against the effect of UV+ H2O2 at 20 and 40 μg/mL doses. In the micronucleus (MN) test, HCQ showed no genotoxicity in lymphocytes at all concentrations (10, 20, or 40 µg/mL) but showed a significant cytotoxic effect, especially at high doses. The Oxidative Stress Index (OSI) calculated from the Total Oxidant Capacity (TOC) and Total Antioxidant Response (TAR) (at 660 nm wavelength) measured spectrophotometrically (at 590 nm) using the cell culture supernatant taken after the first centrifugation in the MN experiment, was significantly higher, especially at high HCQ concentrations were found to decrease. According to in silico molecular docking simulation data, HCQ and DNA polymerase delta interact with weak free binding energy (Gibbs energy = -5.6 kcal/mol). As a general result, HCQ did not show a significant genotoxic effect in this study, but its cytotoxic effect is remarkable. This finding promises a paradigm shift in the treatment of different diseases.