Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity

Food and Chemical Toxicology

Volumn 49, Issue 12, 2011, Pages 3319-3327

  Johnson, W D ^a   Morrissey, R L ^b   Usborne, A L ^b   Kapetanovic, I ^c   Crowell, J A ^c   Muzzio, M ^a   McCormick, D L ^a  

^a IIT RESEARCH INSTITUTE   (United States)

^b Pathology Associates   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Chemoprevention; Resveratrol

Indexed keywords

BILIRUBIN; RESVERATROL;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILIRUBIN BLOOD LEVEL; BLOOD TOXICITY; CARDIOMYOPATHY; CARDIOVASCULAR EFFECT; CHRONIC TOXICITY; CLINICAL EVALUATION; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; EYE TOXICITY; FEMALE; HEART PROTECTION; HISTOPATHOLOGY; MALE; NEUROTOXICITY; NONHUMAN; ORGAN WEIGHT; RAT; WEIGHT REDUCTION;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; BODY WEIGHT; CARDIOTONIC AGENTS; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; FEMALE; KIDNEY; MALE; NO-OBSERVED-ADVERSE-EFFECT LEVEL; ORGAN SIZE; POLYPHENOLS; RATS; STILBENES; TOXICITY TESTS, SUBCHRONIC; URINARY BLADDER;

CANIS FAMILIARIS; RATTUS;

EID: 80054853722     PISSN: 02786915     EISSN: 18736351     Source Type: Journal    
DOI: 10.1016/j.fct.2011.08.023     Document Type: Article

References (41)

1. Bai Y., Mao Q.Q., Qin J., Zheng X.Y., Wang Y.B., Yang K., Shen H.F., Xie L.P. Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo. Cancer Sci. 2010, 101(2):488-493.
2. Banerjee S., Bueso-Ramos C., Aggarwal B.B. Suppression of 7,12-dimethylbenz(a)-anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res. 2002, (62):4945-4954.
3. Berta G.N., Salamone P., Sprio A.E., DiScipio F., Marinos L.M., Sapino S., Carlotti M.E., Cavalli R., DiCarlo F. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch by topical application of resveratrol complexed with 2-hydroxypropyl-beta-cyclodextrin. Oral Oncol. 2010, 46(1):42-48.
4. Bishayee A., Barnes K.F., Bhatia D., Darvesh A.S., Crroll R.T. Resveratrol suppresses oxidative stress and inflammatory response in diethylnitrosamine-initiated rat hepatocarcinogenesis. Cancer Prev. Res. 2010, (6):753-763.
5. Bishayee A., Dhir N. Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: inhibition of cell proliferation and induction of apoptosis. Chem. Biol. Interact. 2009, 179(2-3):131-144.
6. Bowers J.L., Tyulmenkov V.V., Jernigan S.C., Klinge C.M. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endrocrinology 2000, (141):3657-3667.
7. Brisdelli F., D'Andrea G., Bozzi A. Resveratrol: a natural polyphenol with multiple chemopreventive properties. Curr. Drug Metab. 2009, 10(6):530-546.
8. Chun Y.J., Kim M.Y., Guengerich F.P. Resveratrol is a selective human cytochrome P-450 1A1 inhibitor. Biochem. Biophys. Res. Commun. 1999, (262):20-24.
9. Ciolino H.P., Yeh G.C. Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Mol. Pharmacol. 1999, (56):760-767.
10. Crowell J.A., Korytko P.J., Morrissey R.L., Booth T.D., Levine B.S. Resveratrol-associated renal toxicity. Toxicol. Sci. 2004, (82):614-619.
11. Das D.K., Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol. Interventions 2006, (6):36-47.
12. Freyberger A., Hartmann E., Hildebrand H., Krotlinger F. Differential response of immature rat uterine tissue to ethinylestradiol and the red wine constituent resveratrol. Arch. Toxicol. 2001, (74):709-715.
13. Garvin S., Ollinger K., Dabrosin C. Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Lett. 2006, (231):113-122.
14. Harper C.E., Cook L.M., Patel B.B., Wang J., Eltoum I.A., Arabshahi A., Shirai T., Lamartiniere C.A. Genistein and resveratrol, alone and in combination, suppress prostate cancer in SV-40 tag rats. Prostate 2009, 69(15):1668-1682.
15. Henry L.A., Witt D.M. Resveratrol: phytoestrogen effects on reproductive physiology and behavior in female rats. Horm. Behav. 2002, (41):220-228.
16. Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G., Zipkin R.E., Chung P., Kisielewski A., Zhang L.L., Sinclair D.A., Scherer B. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003, (425):191-196.
17. Hung L.M., Chen J.K., Huang S.S., Lee R.S., Su M.J. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc. Res. 2000, (47):549-555.
18. Jang M., Cai L., Udeani G.O., Slowing K.V., Thomas C.F., Beecher C.W., Fong H.H., Farnsworth N.R., Kinghorn A.D., Mehta R.G., Moon R.C., Pezzuto J.M. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997, 275:218-220.
19. Joe A.K., Liu H., Suzui M., Vural M.E., Xiao D., Weinstein I.B. Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin. Cancer Res. 2002, (8):893-903.
20. Juan M.E., Vinardell M.P., Planas J.M. The daily oral administration of high doses of trans-resveratrol to rats for 28days is not harmful. J. Nutr. 2002, (132):257-260.
21. Kai L., Samuel S.K., Levenson A.S. Resveratrol enhances p53 acetylation and apoptosis in prostate cancer by inhibiting MTA1/NuRD complex. Int. J. Cancer. 2010, 126(7):1538-1548.
22. Kraft T.E., Parisotto D., Schempp C., Efferth T. Fighting cancer with red wine? Molecular mechanisms of resveratrol. Crit. Rev. Food Sci. Nutr. 2009, 49(9):782-799.
23. Lee M.H., Choi B.Y., Kundu J.K., Shin Y.K., Na H.K., Surh Y.J. Resveratrol suppresses growth of human ovarian cancer cells in culture and in murine xenograft model: eukaryotic elongation factor 1A2 as a potential target. Cancer Res. 2009, 69(18):7449-7458.
24. Manna S.K., Mukhopadhyay A., Aggarwal B.B. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J. Immununol. 2000, 164:6509-6519.
25. Oi N., Jeong C.H., Nadas J., Cho Y.Y., Pugliese A., Bode A.M., Dong Z. Resveratrol, a red wine polyphenol, suppresses pancreatic cancer by inhibiting leukotriene a4 hydrolase. Cancer Res. 2010, 70(23):9755-9764.
26. Provinciali M., Re F., Donnini A., Orlando F., Bartozzi B., Di Stasio G., Smorlesi A. Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Int. J. Cancer. 2005, (115):36-45.
27. Renaud S., de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992, (339):1523-1526.
28. Roy P., Kalra N., Prasad S., George J., Shukla Y. Chemopreventive potential of resveratrol in mouse skin tumors through regulation of mitochondrial and PI3K/AKT signaling pathways. Pharm. Res. 2009, 26(1):211-217.
29. Sale S., Tunstall R.G., Ruparelia K.C., Potter G.A., Steward W.P., Gescher A.J. Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans 3,4,5,4'-tetramethoxystilbene (DMU-212) on adenoma development in the Apc(Min+) mouse and cyclooxygenase-2 in human-derived colon cancer cells. Int. J. Cancer. 2005, (115):194-201.
30. Sanders T.H., McMichael R.W., Hendrix K.W. Occurrence of resveratrol in edible peanuts. J. Agric. Food Chem. 2000, (48):1243-1246.
31. Subbaramaiah K., Chung W.J., Michaluart P., Telang N., Tanabe T., Inoue H., Jang M., Pezzuto J.M., Dannenberg A.J. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J. Biol. Chem. 1998, (273):21875-21882.
32. Sun B., Hoshino J., Jermihov K., Marler L., Pezzuto J.M., Mesecar A.D., Cushman M. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer. Bioorg. Med. Chem. 2010, 18:5352-5366.
33. Szewczuk L.M., Forti L., Stivala L.A., Penning T.M. Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents. J. Biol. Chem. 2004, (279):22727-22737.
34. Tessitore L., Davit A., Sarotto I., Caderni G. Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21 expression. Carcinogenesis 2000, (21):1619-1622.
35. Tseng S.H., Lin S.M., Chen J.C., Su Y.H., Huang H.Y., Chen C.K., Lin P.Y., Chen Y. Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats. Clin. Cancer Res. 2004, (10):2190-2202.
36. Valenzano D.R., Terzibasi E., Genade T., Cattaneo A., Domenici L., Cellerino A. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr. Biol. 2006, (16):296-300.
37. Wang T.T., Hudson T.S., Wang T.C., Remsberg C.M., Davies N.M., Takahashi Y., Kim Y.S., Seifried H., Vinyard B.T., Perkins S.N., Hursting S.D. Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo. Carcinogenesis 2008, (10):2001-2010.
38. Whyte L., Huang Y.Y., Torres K., Mehta R.G. Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007, 67(24):12007-120017.
39. Williams L.D., Burdock G.A., Edwards J.A., Beck M., Bausch J. Safety studies conducted on high-purity trans-resveratrol in experimental animals. Food Chem. Toxicol. 2009, (47):2170-2182.
40. Woodall C.E., Li Y., Liu Q.H., Wo J., Martin R.C. Chemoprevention of metaplasia initiation and carcinogenic progression to esophageal adenocarcinoma by resveratrol supplementation. Anticancer Drugs 2009, 20(6):437-443.
41. Zhou H.B., Chen J.J., Wang W.X., Cai J.T., Du Q. Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice. World J. Gastroenterol. 2005, 11(2):280-284.