%0 Journal Article
%T Assessment of Anti-Cytogenotoxic Effects of Quercetin in Animals Treated with Topotecan
%A Saleh A. Bakheet
%J Oxidative Medicine and Cellular Longevity
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/824597
%X The present investigation was directed to study the possible chemoprotective activity of orally administered quercetin against topotecan-induced cyto- and genotoxicity towards mouse somatic cells in vivo. DNA strand breaks, micronuclei formation, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Oxidative stress markers such as intracellular reactive oxygen species generation, lipid peroxidation, and reduced and oxidized glutathione were assessed in bone marrow as a possible mechanism underlying this amelioration. Quercetin was neither cytotoxic nor genotoxic in mice at doses tested. Pretreatment of mice with quercetin significantly reduced topotecan-induced genotoxicity and cytotoxicity in bone marrow cells, and these effects were dose dependent. Moreover, prior administration of quercetin ahead of topotecan challenge ameliorated oxidative stress markers. In conclusion, quercetin has a protective role in the abatement of topotecan-induced cyto- and genotoxicity in the bone marrow cells of mice that resides, at least in part, on its antioxidant effects. Based on the data presented, strategies can be developed to decrease the topotecan-induced bone marrow suppression and secondary malignancy in cancer patients and medical personnel exposing to topotecan. 1. Introduction Camptothecin, a pentacyclic alkaloid originally isolated from the Chinese plant Camptotheca acuminata by Wall and Wani in 1996 [1], is one of the most important lead compounds in anticancer research. The antitumor activity of camptothecin is thought to be due to its ability to stabilize the reversible covalent DNA topoisomerase I complex [2, 3], preventing the relegation step of the breakage/rejoining reaction mediated by the enzyme. The net result is that the drug causes fragmentation of chromosomal DNA, cell death, extensive sister chromatid exchange, and chromosomal aberrations [4, 5]. Elucidation of the specific target and mechanisms of camptothecin have stimulated intensive efforts to identify novel analogues that overcome the drawbacks of the natural camptothecin molecule, which include low solubility in water; severe and unpredictable toxicity, including hemorrhagic cystitis; reversibility of the drug-target interaction; lactone instability; drug resistance. One of the initial major strategies in this regard has been to improve the solubility of the natural camptothecin by chemical modification [6]. This approach has produced different series of water-soluble analogues or water-soluble prodrugs, among which topotecan (TPT) and
%U http://www.hindawi.com/journals/omcl/2011/824597/