Selim Manar E, Aleisa Nadia A, Daghestani Maha H
Zoology Department, College of Science, King Saud University, Riyadh, KSA.
Ultrastruct Pathol. 2013 May;37(3):204-17. doi: 10.3109/01913123.2013.772269.
The purpose of this study was to appraise the possible adverse effects of quercetin against the aromatase inhibitor letrozole-induced developmental toxicity potential in male Wistar rats.
Control male albino rats were received vehicles used for flavonoids and vehicle used for letrozole. The rats in the first experimental group received letrozole at 0.04 mg/kg body weight (bwt) for 3 months. The second experimental group was treated with the flavonoid quercetin by gavage at a dose of 50 mg/kg bwt for 10 consecutive days after letrozole administration.
Major treatment-related effects of letrozole included a dose-dependent increase in hormone levels and lipid peroxidation following exposure to 0. 04 mg/kg letrozole; and severe abnormalities with severe cellular deformation and disorganization in both spermatogenic and interstitial cells. The seminiferous tubules of the testes of the animals given quercetin and letrozole exhibited a rather normal appearance and the measured hormone levels were restored to nearly the normal levels.
Exposure doses of letrozole that are equal to the daily recommended human dose has toxic effects on the spermatogenic lineage in rats, while simultaneous treatment of quercetin and letrozole could prevent the deleterious effects on testicular tissue caused by letrozole administration.
本研究旨在评估槲皮素对芳香化酶抑制剂来曲唑诱导的雄性Wistar大鼠发育毒性的潜在不良影响。
对照雄性白化大鼠接受用于黄酮类化合物的赋形剂和用于来曲唑的赋形剂。第一实验组的大鼠接受0.04mg/kg体重的来曲唑,持续3个月。第二实验组在给予来曲唑后连续10天经口灌胃给予50mg/kg体重的黄酮类化合物槲皮素。
来曲唑的主要治疗相关效应包括暴露于0.04mg/kg来曲唑后激素水平和脂质过氧化的剂量依赖性增加;以及生精细胞和间质细胞出现严重的细胞变形和紊乱等严重异常。给予槲皮素和来曲唑的动物睾丸生精小管外观较为正常,且测得的激素水平恢复到接近正常水平。
等于每日推荐人类剂量的来曲唑暴露剂量对大鼠生精谱系有毒性作用,而同时给予槲皮素和来曲唑可预防来曲唑给药对睾丸组织的有害影响。