Assessment of anti-genotoxic Effect of Quercetin in Animals Treated with Topotecan
Bakheet SA
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Abstract:
The objectives of the current investigation are to determine whether non-toxic doses of quercetin can ameliorate genotoxicity induced by topotecan in murine marrow cells. Various cytogenetic techniques were applied such as: DNA strand breaks, chromosomal analysis, mitotic activity and micronucleus assay. Moreover, the possible mechanism underlying this amelioration was assessed by the fluorescein DCFH-DA probe. Quercetin was neither cytotoxic nor genotoxic in mice at doses equivalent to 50 or 100 mg/kg for 2 days. Pre-treatment of mice with quercetin significantly reduced topotecan-induced DNA strand breaks, chromosomal aberrations and micronucleus formation and these effects were dose dependent. Moreover, the mitodepression induced by topotecan was also restored in the quercetin pre-treatment group; however, this amelioration was not significant when compared to the values observed in the group treated with topotecan alone. Topotecan-induced accumulation of DCF fluorescence was profoundly abrogated by quercetin and decreased to the level significantly different from the level of DCF fluorescence in the topotecan treated alone. It is concluded that quercetin has a protective role in the abatement of topotecan-induced genotoxicity in the bone marrow cells of mice that resides, at least in part, on its radical scavenger activity. Therefore, quercetin can be a good candidate to decrease the deleterious effects of topotecan in non-tumor cells of cancer patients treated with topotecan.
