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4-Hydroxyhalcone effects on cisplatin-induced genotoxicity model.
Aref Nazari1, Mina Mirian2, Mahmoud Aghaei3
1Toxicology M.SC Candidate, Isfahan University of Medical Sciences and Health Services, Isfahan 83714, Iran.
Toxicology Research
|February 22, 2021
Summary
This study shows that 4-hydroxychalcone (4-HCH) can reduce the genotoxicity of cisplatin (CP) by lowering reactive oxygen species (ROS) and protecting bone marrow cells. These findings suggest 4-HCH as a potential protective agent against chemotherapy side effects.
Area of Science:
- Pharmacology and Toxicology
- Natural Product Chemistry
- Genetics and Molecular Biology
Background:
- Cisplatin (CP) is a platinum-based antineoplastic agent known for inducing genotoxicity via oxidative stress.
- Reactive oxygen species (ROS) play a critical role in CP-induced cellular damage.
- Natural compounds are being investigated for their potential to mitigate chemotherapy-induced toxicity.
Purpose of the Study:
- To investigate the protective effects of 4-hydroxychalcone (4-HCH), a natural flavonoid, against cisplatin-induced genotoxicity.
- To evaluate the impact of 4-HCH on ROS production and DNA damage in a mouse model.
- To assess the potential of 4-HCH as an adjunct therapy to reduce cisplatin's side effects.
Main Methods:
- Cytotoxicity of CP and 4-HCH was determined using the MTT assay on human embryonic kidney 293 cells.
- Intracellular ROS levels were measured using DCFDA dye following CP exposure.
- A mice model was used to assess 4-HCH's antigenotoxic effects, with micronucleus formation in bone marrow cells quantified after CP administration and 4-HCH treatment (pre- and co-treatment schedules).
Main Results:
- The IC50 values for CP and 4-HCH were approximately 19.4 μM and 133.6 μM, respectively, with 4-HCH showing no significant cytotoxicity at tested concentrations (0.2-10 μM).
- 4-HCH pre-treatment (10 μM) and co-treatment (2 μM) significantly attenuated CP-induced ROS production (P < 0.05 and P < 0.01, respectively).
- The lowest frequency of micronucleated cells was observed in mice treated with 10 mg/kg 4-HCH post-CP exposure (39 ± 7.9, P < 0.0001), indicating significant antigenotoxic activity.
Conclusions:
- 4-hydroxychalcone (4-HCH) demonstrates significant antigenotoxic effects in cisplatin-treated mice bone marrow cells, particularly when administered as a co-treatment.
- These findings provide the first evidence of 4-HCH's protective role against cisplatin-induced genotoxicity in vivo.
- Further research is warranted to explore the clinical application of 4-HCH in combination with cisplatin to mitigate normal cell genotoxicity.
