Associate Professor, Pharmaceutics
Department of Pharmaceutical Sciences
College of Pharmacy
Oregon State University
203 Pharmacy Building
Corvallis, OR 97331-3507
Phone: 541-737-5786
Rosita.Proteau@oregonstate.edu
Rosita Proteau's research page
University of Texas at Austin, B.S., 1991; Ph.D., 1996
Rosita Proteau's research focuses on the development of in vitro cellular models to explore and evaluate the mechanism by which xenobiotics damage or injure specific cell types of various organs or tissues. Rosita works with primary culture systems of liver, heart and skin as experimental models to study the cellular and subcellular toxicity of selected xenobiotics using sensitive indices of cytotoxicity. She also performs drug transport and metabolism studies using a variety of intestinal models. Her current research projects are:
Characterization of intestinal FMOs in human duodenum, jejunum, ileum, colon, and in continuous cell lines from intestinal and colonic origin are being investigated. Human intestinal FMOs will be evaluated for the presence of FMO protein and FMO catalytic activity. Also, direct inhibitory or stimulatory effects of flavonoids will be evaluated using cDNA-expressed human FMOs. Thus, this project will contribute to the knowledge of human intestinal metabolism as well as provide an understanding of the effect of dietary flavonoids on intestinal FMO-mediated metabolism of orally administered therapeutic drugs within the various regions of the digestive tract.
The hypothesis of this study is that exposure of humans to dietary flavonoids can influence drug absorption by altering the P-glycoprotein (Pgp)-dependent or Pgp-independent transport mechanisms (drug-dietary interactions). To test the hypothesis, studies will be conducted to evaluate the role of the free flavonoids (predominant form after intestinal microflora hydrolysis of the glycosylated flavonoid), genistein, naringenin, quercetin and epigallocatechin gallate on Pgp-dependent (3H-digoxin and 3H-cyclosporin) and Pgp-independent transport (3H-tamoxifen and 3H-cimetidine) mechanisms. Also, because the flavonoids generally occur in plants as the glycosylated derivatives, studies will also be conducted on the influence of glycosylated flavonoids, genistin, naringin and quercitrin on Pgp-dependent (3H-digoxin and 3H-cyclosporin) and Pgp-independent transport (3H-tamoxifen and 3H-cimetidine) mechanism.
Fan, Y. and R. Rodriguez-Proteau. "Ketoconazole
modulates multidrug resistant-mediated transport in Caco-2 and MDCKII-MDR1 drug
transport models" in press, Xenobiotica. 2007.
Mata, J.E., Dyal, L.A., Slauson M.E., Loehr, C., Summerton J.E., Tyson, A.R., Rodriguez-Proteau, R., Gustafson, S.B. Tumor imaging using technicium-99m bound to pH sensitive peptides. Nanomedicine. Nanotechnology, Biology, and Medicine, Volume 3, 297 – 305, 2007.
von Borstel Smith, M., Crofoot, K., Rodriguez-Proteau, R., and T.M. Filtz. "Effects of phenytoin and carbamazepine on calcium transport in Caco-2 cells" Toxicology in Vitro. 2007; 21: 855-862.
Rodriguez-Proteau R, Mata JE, Miranda CL, Fan Y, Brown JJ, Buhler DR. Plant Polyphenols and Multi-Drug Resistance: Effects of Dietary Flavonoids on Drug Transporters in Caco-2 and MDCK-MDR1 cell transport models. Xenobiotica. 2006;36:41-58.
Mahadevan B, Mata JE, Albershardt DJ, Stevens JF, Pereira CB, Rodriguez-Proteau R, Baird WM. The effects of red raspberry extract on PAH transport across Calu-3 cell monolayer, an in vitro cell model. International Journal Cancer Prevention. 2005;2:129-141.
Rodriguez-Proteau R, Grant RL. Toxicity Evaluation and Human Risk Assessment of Surface and Ground Water Contaminated by Recycled Hazardous Waste Materials. In: Environmental Impact Assessment of Recycled Wastes on Surface and Ground Waters. Volume 2: Risk Analysis. The Handbook of Environmental Chemistry, Water Pollution Series, Vol. 5/Part F. Heidelberg-New York: Springer-Verlag; 2005:533 pp.
Blatt DH, Pryor WA, Mata JE, Blatt JM, Rodriguez-Proteau R. Reevaluation of the relative potency of synthetic and natural alpha-tocopherol: Experimental observations and clinical trials. Journal of Nutritional Biochemistry. 2004;15:380-395.
Mata JE, Yu Z, Gray JE, Williams DE, Rodriguez-Proteau R. Effects of chlorophyllin on transport of dibenso(a,l)pyrene, 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, and aflatoxin B1 across Caco-2 cell monolayers. Toxicology. 2004;196:117-125.
Rodriguez RJ, Buckholz CJ. Hepatotoxicity of ketoconazole in Sprague Dawley rats: Glutathione depletion, flavin-containing monooxygenases-mediated bioactivation, and hepatic covalent binding. Xenobiotica. 2003;33:429-441.
Grant RL, Rodriguez RJ, Hofelt CS, Haws LC. Evaluation of phthalate Kow Values and the phthalate metabolism factor for use in mutlipathway risk assessment of hazardous waste combustion facilities. Human Ecological Risk Assessment. 2002;8:1137-1154.
Rodriguez RJ, Acosta D. Cardiac Toxicology. In: Sperelakis N, Kurachi Y, Terzic A, Cohen MV, eds. Heart Physiology and Pathophysiology. San Diego: Academic Press; 2001:1211-1224.
Rodriguez RJ, Miranda CL, Stevens JF, Deinzer ML, Buhler DR. Influence of prenylated and non-prenylated flavonoids on liver microsomal lipid peroxidation and oxidative injury in rat hepatocytes. Food and Chemical Toxicology. 2001;39:437-445.
Rodriguez RJ, Miranda CL. Isoform Specificity of N-Deacetyl Ketoconazole by Human and Rabbit lavin-Containing Monooxygenases. Drug Metabolism and Disposition. 2000;28:1083-1086.
Rodriguez RJ, Proteau PJ, Marquez B, Hetherington CL, Buckholz CJ, O'Connell KL. Flavin-containing monooxygenase-mediated metabolism of N-deacetyl ketoconazole in rat hepatic microsomes. Drug Metabolism and Disposition. 1999;27:880-886.
Miranda CL, Stevens JF, Helmrich A, Henderson MC, Rodriguez RJ, Yea-Huey Y, Deinzer ML, Barnes DW, Buhler DR. Antiproliferative and cytotoxic effects of prenylated flavonoids from HOPS (Humulus Lupulus) in human cancer cell lines. Food and Chemical Toxicology. 1999;37:271-285.
Davila JC, Rodriguez RJ, Melchert RB, Acosta D. Predictive value of in vitro model systems in toxicology. Annual Review of Pharmacology and Toxicology. 1998;38:63-96.
Rodriguez RJ, Acosta D. Metabolism of ketoconazole and N-deacetyl ketoconazole by rat hepatic microsomes and flavin-containing monooxygenases. Drug Metabolism and Disposition. 1997;25:772-777.
Rodriguez RJ, Acosta D. N-deacetyl ketoconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology. 1997;117:123-131.
Rodriguez RJ, Acosta D. Inhibition of mitochondrial function in isolated rat liver mitochondria by azole antifungals. Journal of Biochemical Toxicology. 1996;11:127-131.
Rodriguez RJ, Davila JC, Acosta D. Establishment of flavin-containing monooxygenases in hepatic microsomes obtained from primary cultures of rat hepatocytes. Toxicologist. 1996;30:1215.
Rodriguez RJ, Acosta D. Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology. 1995;96:83-92.
Smith PC, Song WQ, Rodriguez RJ. Covalent binding of etodolac acyl glucuronide to albumin in vitro. Drug Metabolism and Disposition. 1992;63:221-223.
