Gentiana lutea root aqueous extract mitigates hydroxyurea-induced genotoxicity through antioxidative action and DNA repair: an in vitro study in healthy human peripheral blood mononuclear cells

Abstract

Hydroxyurea is a chemotherapeutic agent used to treat various conditions, including sickle cell anaemia and myeloproliferative malignancies. However, it has adverse genotoxic effects on normal cells. This in vitro study aimed to explore the genoprotective potential of yellow gentian (Gentiana lutea L.) root extract (GRE) against hydroxyurea-induced DNA damage in primary human peripheral blood mononuclear cells. We measured total phenolic and flavonoid GRE content (TPC and TFC, respectively) and its capacity to scavenge free radicals using the DPPH and ABTS assays. Before exposure to hydroxyurea, mononuclear cells were treated with non-cytotoxic and non-genotoxic GRE concentrations to assess their genoprotective (CBMN assay) and antioxidative effects (PAB and GSH assays). We also wanted to see how they affected the expression of DNA repair genes PARP1, OGG1, and MnSOD. GRE TPC was 8.42 mg GAE/g while the TFC was below the detection limit. Even so, GRE displayed radical-scavenging activity and restored hydroxyurea-disrupted cellular redox homeostasis, as PAB values returned to normal and GSH levels rose. GRE pre-treatment significantly reduced hydroxyurea-induced DNA damage in a concentration-dependent manner. PARP1 and MnSOD were upregulated, but not OGG1, which indicates GRE's selective action. Our findings confirm its genoprotective effects against hydroxyurea-induced DNA damage in peripheral blood mononuclear cells, indicate a complex mechanism of action, and call for further research of this promising compound against secondary genotoxic effects of hydroxyurea.