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Identification of compound causing yellow bone discoloration following alpha-glycosyl isoquercitrin exposure in Sprague-Dawley rats.
Archives of Toxicology ( IF 4.8 ) Pub Date : 2020-05-09 , DOI: 10.1007/s00204-020-02760-z
Jeffrey P Davis 1 , Mihoko Koyanagi 2 , Robert R Maronpot 3 , Leslie Recio 1 , Shim-Mo Hayashi 4
Affiliation  

Previous rat toxicity studies of alpha-glycosyl isoquercitrin (AGIQ), a water-soluble flavonol glycoside derived from rutin, revealed systemic yellow bone discoloration. This investigative study was conducted to determine the AGIQ metabolite(s) responsible for the discoloration. Female Sprague-Dawley rats were administered dietary AGIQ at doses of 0%, 1.5%, 3.0%, or 5.0% (0, 1735.0, 3480.8, and 5873.7 mg/kg/day, respectively) for 14 days, followed by a 14- or 28-day recovery period. Measurements of quercetin in urine and quercetin, quercetin 3-O-glucuronide, kaempferol, and 3-o-methylquercetin metabolites of AGIQ in bone (femur), white and brown fat, and cerebrum samples were conducted following the exposure period and each recovery period. Gross examination of the femur revealed yellow discoloration that increased in intensity with dose and was still present in a dose-related manner following both recovery periods. Quercetin, at levels correlating with AGIQ dose, was measured in the urine following the 14-day exposure period and, at lower concentrations, 14 or 28 days following cessation of AGIQ exposure. All four metabolites were present in a dose-dependent manner in the femur following 14 days of dietary exposure; only quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were present during the recovery periods. Quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were detected in white fat (along with kaempferol), brown fat (excluding quercetin due to analytical interference), and cerebrum samples, indicating systemic availability of the metabolites. Collectively, these data implicate quercetin, quercetin 3-O-glucuronide, or 3-o-methylquercetin (or a combination thereof) as the most likely metabolite of AGIQ causing the yellow discoloration of bone in rats administered dietary AGIQ.

中文翻译:

鉴定在Sprague-Dawley大鼠中暴露于α-糖基异槲皮苷后导致黄骨变色的化合物。

以前的大鼠毒性研究表明,α-糖基异槲皮苷(AGIQ)是一种源自芦丁的水溶性黄酮醇苷,显示出全身性黄骨变色。进行了这项调查研究,以确定引起变色的AGIQ代谢产物。雌性Sprague-Dawley大鼠的饮食AGIQ剂量为0%,1.5%,3.0%或5.0%(分别为0、1735.0、3480.8和5873.7 mg / kg /天),持续14天,然后进行14-或28天的恢复期。在暴露期和每个恢复期之后,对尿液中的槲皮素和槲皮素,AGIQ的槲皮素3-O-葡萄糖醛酸,山ka酚和3-O-甲基槲皮素,骨(股骨),白色和棕色脂肪以及大脑中的代谢物进行测量。 。股骨的大体检查显示黄色变色,其强度随剂量而增加,并且在两个恢复期之后仍以剂量相关的方式存在。在暴露14天后,在尿液中测量与AGIQ剂量相关的槲皮素,在较低浓度下,停止AGIQ后14或28天测量槲皮素。饮食暴露14天后,股骨中所有四种代谢物均呈剂量依赖性。在恢复期仅存在槲皮素,槲皮素3-O-葡萄糖醛酸苷和3-o-甲基槲皮素。在白色脂肪(与山奈酚一起),棕色脂肪(由于分析干扰而导致的槲皮素除外)和大脑样品中检测到槲皮素,槲皮素3-O-葡萄糖醛酸和3-o-甲基槲皮素,表明这些代谢物的系统可用性。
更新日期:2020-05-09
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