Resveratrol, (3,5,4'-trihydoxystilbene) a compound found in grapes, mulberries, and peanuts, has antimycotic,
antiviral, and beneficial cardiovascular and
cancer preventive activities. It is being developed for several clinical indications. To evaluate the potential toxicity of
resveratrol, rats were administered by gavage 0, 300, 1000, and 3000 mg
trans-resveratrol per kilogram
body weight per day for 4 weeks. Most of the adverse events occurred in the rats administered 3000 mg per kilogram
body weight per day. These included increased clinical signs of toxicity; reduced final
body weights and food consumption; elevated BUN,
creatinine,
alkaline phosphatase,
alanine aminotransferase, total
bilirubin, and
albumin; reduced
hemoglobin, hematocrit, and red cell counts; and increased white cell counts. Increases in kidney weights and clinically significant renal lesions, including an increased incidence and severity of nephropathy, were observed. Diffuse epithelial
hyperplasia in the bladder was considered, equivocal and of limited biological significance. No histological effects on the liver were observed, despite the clinical chemistry changes and increased liver weights in the females. Effects seen in the group administered 1000 mg
resveratrol per kilogram
body weight per day included reduced
body weight gain (females only) and elevated white blood cell count (males only). Plasma
resveratrol concentrations in blood collected 1 h after dose administration during week 4 were dose related but were relatively low given the high dosage levels; conjugates were not measured. Under the conditions of this study, the no observed adverse effect level was 300 mg
resveratrol per kilogram
body weight per day in rats.