Genoprotective and Genotoxic Effects of Thymoquinone on Doxorubicin-Induced Damage in Isolated Human Leukocytes

Purpose: To investigate the potential genoprotective effects of thymoquinone (TQ) on the cytotoxicity and genotoxicity-induced by doxorubicin (DXR), a key chemotherapeutic drug.
Methods: Isolated human peripheral leukocytes were treated with varying concentrations of TQ (5.0, 10.0, or 20.0 μM) alone or in combination with DXR (0.15 μg/mL). Comet assays and apoptotic cell studies were performed to evaluate the effect of TQ on the cytotoxicity and genotoxicity-induced by DXR.
Results: TQ treatment, alone, (5.0, 10, or 20 μM) increased DNA damage index (DI) in a concentrationdependent manner (0.64 ± 0.09, 0.84 ± 0.07, and 0.93 ± 0.06, respectively). DXR (0.15 μg/mL) increased DI (1.67 ± 0.09) compared with no treatment (0.34 ± 0.03). However, when TQ was administered with DXR, DI was significantly reduced (0.96 ± 0.04, 0.80 ± 0.05, and 0.79 ± 0.04) compared with DXR alone (1.67 ± 0.09). Similarly, apoptotic cells decreased (10.8, 11.8 and 14.2 %) compared with that induced by DXR alone (27.6 %).
Conclusion: TQ can be used as a genoprotective agent against DXR-induced genotoxicity. The dual behavior of TQ observed in this study is dose-dependent and therefore its mechanism of action needs to be clarified in future studies.

Keywords
Thymoquinone; Genotoxicity; Genoprotection; Doxorubicin; Apoptotic; Oxidative stress; DNA damage index