4-Hydroxyhalcone effects on cisplatin-induced genotoxicity model.

Abstract

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. 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 40mg/kg/BW doses as a pre and post-treatment schedule in a mice model of CP genotoxicity (7mg/kg). Acridine-orange-stained bone marrow cells were quantified for micronucleus presence examination. The calculated IC50 of CP and 4-HCH were reported around 19.4 and 133.6μM, respectively, on HEK293 cells. Also, it was observed that 4-HCH at 0.2, 2 and 10μM concentrations did not show obvious cytotoxicity. The fluorimetry confirmed that pre-treatment with 10μM and co-treatment with 2μM 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 10mg/kg 4-HCH-treated group after CP exposure (39±7.9, P<0.0001). 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 40mg/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.