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Elfarra, Adnan A.

Adnan A. Elfarra, PhD
Professor
PI Pre- and Post-Doctoral Training Grant

Research Area: Toxicant and carcinogen metabolism. Mechanisms of toxicity and target organ selectivity. DNA and hemoglobin modifications. Toxicity of the industrial chemicals trichloroethylene, tetrachloroethylene, 1,3-butadiene, and related compounds.

Home Dept: Compartive Biosciences, School of Veterinary Medicine
Affiliated Depts: Molecular and Environmental Toxicology; Pharmaceutical Sciences graduate program; Chemistry-Biology and Biotechnology Training Grants

Address
3154 Veterinary Medicine Bldg
2015 Linden Dr
Madison, WI 53706
608/262-6518 - Email

Patents
1992-Protection against chemically-induced kidney damage by methimazole
1992-Prodrugs of 6-mercaptopurine and 6-thioguanine

Research
Metabolic basis of conjugated diene toxicity; biochemical and molecular characterization of flavin-containing monooxygenases; biochemical mechanisms of nephrotoxicity; synthesis and evaluation of kidney-selective prodrugs of anticancer agents.

Current research focuses on the biochemical mechanisms of toxicity of three important industrial chemicals, 1,3-butadiene, styrene, and trichloroethylene, which are also released into the environment and have been associated with carcinogenicity, hepatotoxicity, and nephrotoxicity.

Modern chemical, biochemical, and toxicological techniques are used to investigate the mechanisms of toxicity. For example, the enzymes involved in bioactivation and detoxication of these chemicals are isolated and characterized, to determine if expression of these enzymes in different tissues, and/or species is an important determinant of species, gender, tissue and/or age-related differences in toxicity. In addition, toxicant-derived reactive metabolite adducts with blood protein and DNA are characterized to develop sensitive biomarkers for exposure.

The knowledge gained regarding the biochemical basis of tissue selectivity of various toxicants is also used in this laboratory to design and develop new therapeutic agents that would have greater tissue selectivity and less systemic toxicity than existing drugs.

Publications
  • Novick RM, Elfarra AA. Purification and Characterization of Flavin-Containing Monooxygenase Isoform 3 from Rat Kidney Microsomes. Drug Metab Dispos. 2008 Sep 5. [Epub ahead of print]
  • Barshteyn N, Elfarra AA. Formation of Three N-Acetyl-l-cysteine Monoadducts and One Diadduct by the Reaction of S-(1,2-Dichlorovinyl)-l-cysteine Sulfoxide with N-Acetyl-l-cysteine at Physiological, Conditions: Chemical Mechanisms and Toxicological Implications. Chem Res Toxicol. 2007 Sep 25; [Epub ahead of print]
  • Eklund BI, Gunnarsdottir S, Elfarra AA, Mannervik B. Human glutathione transferases catalyzing the bioactivation of anticancer thiopurine prodrugs. Biochem Pharmacol. 2007 Jun 1;73(11):1829-41.
  • Elfarra AA, Krause RJ. S-(1,2,2-Trichlorovinyl)-L-Cysteine Sulfoxide, a Reactive Metabolite of S-(1,2,2-Trichlorovinyl)-L-Cysteine Formed in Rat Liver and Kidney Microsomes, is a Potent Nephrotoxicant. J Pharmacol Exp Ther. 2007 321(3):1095-101.
  • Krause RJ, Glocke SC, Sicuri AR, Ripp SL, Elfarra AA. Oxidative metabolism of seleno-L-methionine to L-methionine selenoxide by flavin-containing monooxygenases. Chem Res Toxicol. 2006 Dec;19(12):1643-9.
  • Dever JT, Elfarra AA. In vivo metabolism of L-methionine in mice: evidence for stereoselective formation of methionine-d-sulfoxide and quantitation of other major metabolites. Drug Metab Dispos. 2006 Dec;34(12):2036-43.
  • Barshteyn N, Krause RJ, Elfarra AA. Mass spectral analyses of hemoglobin adducts formed after in vitro exposure of erythrocytes to hydroxymethylvinyl ketone. Chem Biol Interact. 2007 166(1-3): 176-81.
  • Zhang XY, Elfarra AA. Characterization of 1,2,3,4-diepoxybutane-2'-deoxyguanosine cross-linking products formed at physiological and nonphysiological conditions. Chem Res Toxicol. 2006 Apr;19(4):547-55.
  • Sprague CL, Elfarra AA. Protection of rats against 3-butene-1,2-diol-induced hepatotoxicity and hypoglycemia by N-acetyl-l-cysteine. Toxicol Appl Pharmacol. 2005 Sep 15;207(3):266-74.
  • Zhang XY, Elfarra AA. Reaction of 1,2,3,4-diepoxybutane with 2'-deoxyguanosine: initial products and their stabilities and decomposition patterns under physiological conditions. Chem Res Toxicol. 2005 Aug;18(8):1316-23.
  • Elfarra AA, Krause RJ. Potential roles of flavin-containing monooxygenases in sulfoxidation reactions of l-methionine, N-acetyl-l-methionine and peptides containing l-methionine. Biochim Biophys Acta. 2005 Jan 17;1703(2):183-9.
Check PubMed for other publications by Adnan A. Elfarra

Date Last Updated: 09/29/2008 webteam@med.wisc.edu