Range-Finding Report on the Immunotoxicity of Trans-Resveratrol in Male B6C3F1 Mice (CAS No. 501-36-0)
Report Date: February 2011
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
trans-Resveratrol is a polyphenol that occurs naturally in grapes, peanuts, and a number of other plants. It is found in foods/drinks made from grapes and peanuts, and also in a number of herbal remedies, both alone and as part of plant extracts. Human exposure to resveratrol compounds is mainly through ingestion, particularly of grapes, peanuts, and their products. RVT has long been found in herbal medicines, and is produced commercially by several companies. Health claims of oral dietary supplements containing trans-resveratrol include protection from free-radical damage, inhibition of arthritic inflammation, inhibition of the cyclooxygenase-2 enzyme, protection of blood vessels, protection against cardiovascular disease and cancer, and alleviation of menopausal symptoms. Preliminary data from NTP 14-day toxicity studies suggest that trans-resveratrol may induce thymic atrophy in male B6C3F1 mice. A review of the literature failed to reveal data related to the immunotoxicity of RVT (National Institute of Environmental Health Sciences, 2002).
The National Toxicology Program requested that a dose range-finding study be performed to establish the potential effects of RVT on the immune system. These studies were conducted in male B6C3F1 mice. Five RVT dose levels (156, 312, 625, 1250, and 2500 mg/kg) for 28 days were utilized. RVT was prepared, as a suspension in the vehicle 0.5% methylcellulose, no more than 42 days in advance and stored frozen in amber vials until use.
Administration of RVT did not adversely affect body weight, body weight gain, or the major organs of the immune system, the thymus and the spleen. Nine animals that received RVT did not survive to the study termination date. Gross examination suggested impaction of the test article in the intestines of the animals. Absolute values of splenic phenotypes in general were unaffected. Treatment with RVT had no effect on the plaque assay, sRBC ELISA, or KLH ELISA, all indicators of effects on humoral immunity. Furthermore, no effects were observed on the MLR, CTL, or anti-CD3 mediated proliferation assays used to evaluate cell-mediated immunity. In addition, two assays to evaluate innate immunity, NK activity and the functional activity of the mononuclear phagocytic system, were not affected by treatment with RVT in male B6C3F1 mice.
|sRBC||sheep red blood cells|
|ELISA||enzyme-linked immunosorbent assay|
|KLH||keyhole limpet hemocyanin|
|MLR||mixed leukocyte response|
|CTL||cytotoxic T lymphocyte|
|CD||cluster of differentiation|
|MPS||mononuclear phagocytic system|
NIEHS. (2002). trans-Resveratrol [501-36-0] Review of Toxicological Literature, NIEHS Document, March 2002.