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Cited by 688

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in Healthy Volunteers: Safety, Pharmacokinetics, and Effect on the Insulin-like Growth Factor Axis

Open access
Brown, Victoria A., Patel, Ketan R., Viskaduraki, Maria, Crowell, James A., Perloff, Marjorie, Booth, Tristan D., Vasilinin, Grygoriy, Sen, Ananda, Schinas, Anna Maria, Piccirilli, Gianfranca, Brown, Karen, Steward, William P., Gescher, Andreas J., Brenner, Dean E.·2010·Cancer Research

Abstract

Resveratrol, a naturally occurring polyphenol, has cancer chemopreventive properties in preclinical models. It has been shown to downregulate the levels of insulin-like growth factor-1 (IGF-I) in rodents. The purpose of the study was to assess its safety, pharmacokinetics, and effects on circulating levels of IGF-I and IGF-binding protein-3 (IGFBP-3) after repeated dosing. Forty healthy volunteers ingested resveratrol at 0.5, 1.0, 2.5, or 5.0 g daily for 29 days. Levels of resveratrol and its metabolites were measured by high performance liquid chromatography-UV in plasma obtained before and up to 24 hours after a dose between days 21 and 28. IGF-I and IGFBP-3 were measured by ELISA in plasma taken predosing and on day 29. Resveratrol was safe, but the 2.5 and 5 g doses caused mild to moderate gastrointestinal symptoms. Resveratrol-3-O-sulfate, resveratrol-4′-O-glucuronide, and resveratrol-3-O-glucuronide were major plasma metabolites. Maximal plasma levels and areas under the concentration versus time curve for the metabolites dramatically exceeded those for resveratrol, in the case of areas under the concentration versus time curve, by up to 20.3-fold. Compared with predosing values, the ingestion of resveratrol caused a decrease in circulating IGF-I and IGFBP-3 (P < 0.04 for both), respectively, in all volunteers. The decrease was most marked at the 2.5 g dose level. The results suggest that repeated administration of high doses of resveratrol generates micromolar concentrations of parent and much higher levels of glucuronide and sulfate conjugates in the plasma. The observed decrease in circulating IGF-I and IGFBP-3 might contribute to cancer chemopreventive activity. Cancer Res; 70(22); 9003–11. ©2010 AACR.

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Metadata

Authors
Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A., Perloff, M., Booth, T. D., Vasilinin, G., Sen, A., Schinas, A. M., Piccirilli, G., Brown, K., Steward, W. P., Gescher, A. J., & Brenner, D. E.
Venue
Cancer Research
Published
2010-11-14
Volume
70
Issue
22
Pages
9003-9011
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2152036317
Cited by
688
References
34
FWCI
13.76
Type
journal article
Language
en
Open access
bronze

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Brown, V. A., Patel, K. R., Viskaduraki, M., Crowell, J. A., Perloff, M., Booth, T. D., Vasilinin, G., Sen, A., Schinas, A. M., Piccirilli, G., Brown, K., Steward, W. P., Gescher, A. J., & Brenner, D. E. (2010). Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in Healthy Volunteers: Safety, Pharmacokinetics, and Effect on the Insulin-like Growth Factor Axis. Cancer Research. https://doi.org/10.1158/0008-5472.can-10-2364

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