4-Hydroxyhalcone effects on cisplatin-induced genotoxicity model

Abstract

Background: The genotoxicity of cisplatin (CP) as a platinum-based antineoplastic agent due to its oxidative stress induction was well known. In this research, we examined 4-hydroxychalcone (4-HCH) as a natural food that presents flavonoid effects on reactive oxygen species (ROS) production and CP-induced in vivo genotoxicity. Method and materials: Cytotoxicity of CP and 4-HCH was measured on human embryonic kidney 293 cells with MTT assay. Then, intracellular ROS content at IC50 concentration of CP was measured with 2′,7′-dichlorofluorescein diacetate (DCFDA) dye. Finally, 4-HCH was administered intraperitoneally at 10 and 40 mg/kg/BW doses as a pre and post-treatment schedule in a mice model of CP genotoxicity (7 mg/kg). Acridine-orange-stained bone marrow cells were quantified for micronucleus presence examination. Results: The calculated IC50 of CP and 4-HCH were reported around 19.4 and 133.6 μM, respectively, on HEK293 cells. Also, it was observed that 4-HCH at 0.2, 2 and 10 μM concentrations did not show obvious cytotoxicity. The fluorimetry confirmed that pre-treatment with 10 μM and co-treatment with 2 μM of 4-HCH could attenuate the CP-induced ROS production (P < 0.05 and P < 0.01, respectively). Also, the lowest micronucleated cells were seen in 10 mg/kg 4-HCH-treated group after CP exposure (39 ± 7.9, P < 0.0001). Discussion: Our results demonstrated the antigenotoxic action of 4-HCH in CP-treated mice bone marrow cells for the first time in both concentrations of 10 and 40 mg/kg especially in the form of co-treatment. Further studies required clinical application of this compound in a combination of CP to attenuate the normal cells' genotoxicity side effects.