Amelioration of Doxorubicin-induced genotoxicity in isolated cultured human lymphocytes by Thymoquinone.
Journal Title: Applied Science Reports - Year 2013, Vol 4, Issue 2
Abstract
In spite of the successful use of Thymoquinone (TQ) as antioxidant and antimutagenic in many studies, it was not tried yet against the genotoxic effect of Doxorubicin (DOX) in isolated cultured human lymphocytes. Hence, the present study was conducted to investigate the possible antioxidant genoprotective effects of TQ (1 μM )on the chromosomal injury induced by DOX (0.15 μg/ml ) in isolated cultured human lymphocytes in comparison with the well-known antioxidants L-Carnosine (L-Car) 20 mM and Curcumin (CMN) 15 μM. After the end of cultured period (72 hr), the levels of chromosomal aberrations (CAs); mitotic index (MI); reduced glutathione (GSH); malondialdehyde (MDA); and 8-hydroxydeoxyguanosine (8-OH-dG) were measured. DOX caused oxidative genotoxic effect as shown by significant increase in the levels of structural CAs, MDA and 8-OH-dG together with significant decrease in the levels of MI and GSH when compared to non treated group. DOX-induced toxic changes were significantly ameliorated when combined with TQ, L-Car or CMN with the highest protection for TQ > L-Car > CMN. The genoprotective effects of TQ, L-Car and CMN were mainly due to antioxidant activity as shown by decreased MDA and 8-OH-dG together with increased GSH. The higher activity of TQ over L-Car and CMN might be explained by the difference in structure where TQ has least molecular weight that allow it to penetrate cell wall and act efficiently on the level of cytosole and DNA. However, CMN has the highest molecular weight that limits its action to the level of lipid membranes.
Authors and Affiliations
Mahmoud A Naga, Mohamed A Abd El-Aziz, Sabry M Zeid, Zeid1Mohamad-Hesham Y Daba, Nadia K El-Gamal
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