Evaluation of in vitro cytotoxic and genotoxic effects of the 3‐(3,4‐dihydroxyphenyl)‐8‐hydroxycoumarin

Abstract

AbstractA wide variety of natural and synthetic coumarins present therapeutic potential. Therefore, the assessment of their safety for humans is essential. 3‐(3,4‐Dihydroxyphenyl)‐8‐hydroxycoumarin is a coumarin derivative with antioxidant properties, among other biological activities. The aim of this study is to evaluate the cytotoxic and genotoxic potential of this molecule on peripheral blood mononuclear cells (PBMC) and human hepatocellular carcinoma cells (HepG2/C3A). The results obtained for the cytotoxicity assays, evaluated by the trypan blue staining assay, using concentrations between 0.1 and 20 μg/mL, showed that there is no decrease in cell viability for both cell lines. The MTT assay showed a significant decrease in the viability of HepG2/C3A cells at the highest concentrations tested, after 48 h, for all the tested concentrations, after 72 h of exposure. Regarding the genotoxic assays, the data obtained by the comet assay and the micronucleus test, up to the tested concentration of 10 μg/mL, do not show significant DNA damage and/or chromosomal mutations, for both cell lines. However, at the highest tested concentration of 20 μg/mL, a small but significant genotoxic effect was observed in PBMC. In view of the observed results, it can be concluded that the 3‐(3,4‐dihydroxyphenyl)‐8‐hydroxycoumarin, up to a concentration of 10 μg/mL, does not present genotoxic effects in human cells with and without liver enzymes metabolism. Additional studies with higher concentrations of this molecule need to be performed to address its complete biosafety.