Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Ramadan I Al-Shdefat¹, Mohamed A Abd-ElAziz² , Fahad I Al-Saikhan²

¹Department of Pharmaceutics; ²Department of Clinical Pharmacy, College of Pharmacy, Salman Bin Abdulaziz University, Riyadh, Al-kharj 11942, Saudi Arabia.

For correspondence:- Mohamed Abd-ElAziz Email: m.abdelmotaal@sau.edu.sa

Received: 8 July 2014 Accepted: 27 October 2014 Published: 15 December 2014

Citation: Al-Shdefat RI, Abd-ElAziz MA, Al-Saikhan FI. Genoprotective and Genotoxic Effects of Thymoquinone on Doxorubicin-Induced Damage in Isolated Human Leukocytes. Trop J Pharm Res 2014; 13(12):2015-2020 doi: 10.4314/tjpr.v13i12.10

© 2014 The authors.
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Abstract

Purpose:To investigate the potential genoprotective e@256;ects 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 concentration-dependent 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 signi@257;cantly 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