الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Background: Doxorubicin (DOX) is anticancer drug used in the treatment of several types of human malignancies. It has many toxic effects including cardiotoxicity, cytotoxicity, and genotoxicity. Phenytoin (PHT) is another drug has been suspected of teratogenic and mutagenic effects during pregnancy. There is a strong debate around the phenytoin-induced genotoxic effects. Many naturally occurring compounds have been reported to have antioxidant and anti-mutagenic activities such as L-carnosine (L-car), Thymoquinone (TQ) and Curcumin (CMN).
Methods: This study was conducted to investigate the possible antioxidant genoprotective effects of L-car, CMN, and TQ on chromosomal injury induced by DOX using isolated cultured human lymphocytes. In addition, this work investigated the genotoxic effect of PHT in comparison to DOX genotoxicity. The effects in the cultured human lymphocytes were measured by; (1) chromosomal aberrations (CAs); (2) Mitotic index; (3) reduced glutathione (GSH); (4) malondialdehyde (MDA), and (5) 8-hydroxydeoxyguanosine (8-OH-dG).
Results: DOX caused obvious genotoxic effect indicated by increased CAs, MDA and 8-OH-dG with decreased MI and GSH. However, apart from decreased lymphocyte proliferation indicated by MI, PHT 60, 90 ug/ml did not show significant genotoxic effect in this study. Additionally, PHT (120 ug/ml) caused obvious cytotoxic effect indicated by death of most of cells. The genoprotective and antioxidant effects of L.car, CMN, and TQ against adriamycin-induced genotoxicity in the isolated cultured human lymphocytes were significant with the protective effect of TQ>L-car>CMN. However, the cytotoxic effects of PHT were not reduced by L. car, TQ or CMN; indicating a direct toxic effect.
Conclusion: The genotoxic effect of DOX could be ameliorated using the antioxidant genoprotective effects of L.car, TQ or CMN. PHT it self is not genotoxic in isolated human lymphocytes without metabolic conversion to its active metabolite and that its direct cytotoxicity not occurs except with large doses.