Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity.
Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity.
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DOI：
10.1016/j.fct.2011.08.023
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发表时间：
2011-12
影响因子：
4.3
通讯作者：
McCormick, D. L.
中科院分区：
文献类型：
--
作者：
Johnson, W. D.;Morrissey, R. L.;Usborne, A. L.;Kapetanovic, I.;Crowell, J. A.;Muzzio, M.;McCormick, D. L.
为了表征白藜芦醇的亚慢性经口毒性，CD大鼠每天接受0、200、400或1000 mg白藜芦醇/kg/天的灌胃剂量，比格犬每天接受0、200、600或1200 mg白藜芦醇/kg/天的胶囊剂量，持续90天。白藜芦醇仅引起极轻微的毒性，包括雌性大鼠和两种性别犬的体重增加的剂量相关性降低，以及1000 mg/kg/天剂量下大鼠胆红素水平的统计学显著性增加。临床观察、血液学、眼科学、神经毒性评价（功能观察组合）、器官重量和大体病理学均未提供白藜芦醇在两个种属中具有生物学显著性的证据。在大鼠中，高剂量的白藜芦醇降低了心肌病的发病率;没有看到其他微观变化。犬的组织学变化仅限于肾脏和膀胱中的极轻微炎性浸润，认为其不具有毒理学显著性。在犬中进行的心血管安全药理学（遥测）研究显示，没有证据表明白藜芦醇具有毒性。基于体重效应，白藜芦醇的无明显不良作用水平（NOAEL）在大鼠中为200 mg/kg/天，在犬中为600 mg/kg/天。白藜芦醇在大鼠中的明显心脏保护活性表明，其潜在的有益活性可能超出癌症预防的功效。
To characterize the subchronic oral toxicity of resveratrol, CD rats received daily gavage doses of 0, 200, 400, or 1000 mg resveratrol/kg/day, and beagle dogs received daily capsule doses of 0, 200, 600, or 1200 mg resveratrol/kg/day for 90 days. Resveratrol induced only minimal toxicity, consisting of dose-related reductions in body weight gain in female rats and both sexes of dogs, and a statistically significant increase in bilirubin levels in rats at the 1000 mg/kg/day dose. Clinical observations, hematology, ophthalmology, neurotoxicity evaluations (functional observational batteries), organ weights, and gross pathology provided no biologically significant evidence of resveratrol toxicity in either species. In rats, the high dose of resveratrol reduced the incidence of cardiomyopathy; no other microscopic changes were seen. Histopathologic changes in dogs were limited to minimal inflammatory infiltrates in the kidney and urinary bladder, which were not considered toxicologically significant. A cardiovascular safety pharmacology (telemetry) study in dogs revealed no evidence of resveratrol toxicity. Based on body weight effects, the No Observed Adverse Effect Level (NOAEL) for resveratrol was 200 mg/kg/day in rats and 600 mg/kg/day in dogs. The apparent cardioprotective activity of resveratrol in rats demonstrates that its potentially beneficial activities may extend beyond efficacy in cancer prevention.
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影响因子：
6.1
作者：
Freyberger, A;Hartmann, E;Krötlinger, F
通讯作者：
Krötlinger, F
影响因子：
4.4
作者：
Manna, SK;Mukhopadhyay, A;Aggarwal, BB
通讯作者：
Aggarwal, BB
影响因子：
6.4
作者：
Sale, S;Tunstall, RG;Gescher, AJ
通讯作者：
Gescher, AJ
影响因子：
5.7
作者：
Bai, Yu;Mao, Qi-Qi;Xie, Li-Ping
通讯作者：
Xie, Li-Ping
影响因子：
2.8
作者：
Harper, Curt E.;Cook, Leah M.;Patel, Brijesh B.;Wang, Jun;Eltoum, Isam A.;Arabshahi, Ali;Shirai, Tomoyuki;Lamartiniere, Coral A.
通讯作者：
Lamartiniere, Coral A.