4-Hydroxyhalcone effects on cisplatin-induced genotoxicity model.

Abstract

Background\nThe 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.\n\n\nMethod and materials\nCytotoxicity 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\xa0mg/kg/BW doses as a pre and post-treatment schedule in a mice model of CP genotoxicity (7\xa0mg/kg). Acridine-orange-stained bone marrow cells were quantified for micronucleus presence examination.\n\n\nResults\nThe calculated IC50 of CP and 4-HCH were reported around 19.4 and 133.6\xa0μM, respectively, on HEK293 cells. Also, it was observed that 4-HCH at 0.2, 2 and 10\xa0μM concentrations did not show obvious cytotoxicity. The fluorimetry confirmed that pre-treatment with 10\xa0μM and co-treatment with 2\xa0μM of 4-HCH could attenuate the CP-induced ROS production (P\xa0<\xa00.05 and P\xa0<\xa00.01, respectively). Also, the lowest micronucleated cells were seen in 10\xa0mg/kg 4-HCH-treated group after CP exposure (39\xa0±\xa07.9, P\xa0<\xa00.0001).\n\n\nDiscussion\nOur 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\xa0mg/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.