Aref Nazari1, Mina Mirian2, Mahmoud Aghaei3, Mehdi Aliomrani4. 1. Toxicology M.SC Candidate, Isfahan University of Medical Sciences and Health Services, Isfahan 83714, Iran. 2. Department of Pharmaceutical Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences and Health Services, Isfahan 83714, Iran. 3. Department of Clinical Biochemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan 83714, Iran. 4. Department of Toxicology and Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences and Health Services, Isfahan 83714, Iran.
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.
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.
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