Department of Pharmacology, College of Pharmacy, King Saud University, PO 2457, Riyadh 11451, Saudi Arabia.
Mutagenesis. 2010 May;25(3):281-8. doi: 10.1093/mutage/geq004. Epub 2010 Feb 15.
The aim of the present investigation is to determine whether the quercetin in combination with cisplatin can ameliorate cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice. The scoring of chromosomal aberrations, micronuclei and mitotic activity were undertaken in the current study as markers of clastogenicity. Apoptosis was analysed by the Annexin V-propidium iodide assay and the occurrence of a hypodiploid DNA peak. Oxidative stress markers such as bone marrow lipid peroxidation and reduced glutathione were assessed as a possible mechanism underlying this amelioration. Quercetin was neither clastogenic nor apoptogenic in mice at doses equivalent to 50 or 100 mg/kg for 2 days. Pre-treatment of mice with quercetin significantly reduced cisplatin-induced clastogenesis and apoptosis in the bone marrow cells and these effects were dose and time dependent. Prior administration of quercetin ahead of cisplatin challenge ameliorated oxidative stress markers. Overall, this study provides for the first time that quercetin has a protective role in the abatement of cisplatin-induced clastogenesis and apoptosis in the bone marrow cells of mice that resides, at least in part, in its antioxidant effects. Therefore, quercetin can be a good candidate to decrease the deleterious effects of cisplatin in the bone marrow cells of cancer patients treated with this drug.
本研究旨在探讨槲皮素联合顺铂是否可以减轻顺铂诱导的小鼠骨髓细胞的断裂和凋亡。本研究采用染色体畸变、微核和有丝分裂活性评分作为断裂剂的标志物。通过 Annexin V-碘化丙啶检测和低倍体 DNA 峰的出现来分析细胞凋亡。氧化应激标志物，如骨髓脂质过氧化和还原型谷胱甘肽，被评估为这种改善的可能机制。在相当于 50 或 100mg/kg 的剂量下，2 天的时间内，槲皮素对小鼠既没有断裂作用也没有凋亡作用。用槲皮素预先处理小鼠可显著减轻顺铂诱导的骨髓细胞断裂和凋亡，这些作用具有剂量和时间依赖性。在顺铂挑战之前给予槲皮素可改善氧化应激标志物。总的来说，这项研究首次表明，槲皮素在减轻顺铂诱导的小鼠骨髓细胞断裂和凋亡方面具有保护作用，至少部分原因在于其抗氧化作用。因此，槲皮素可以作为一种候选药物，减少癌症患者在接受顺铂治疗时骨髓细胞的有害作用。
