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Education:

• B.S. 1975 Pharmacy Cairo University
• PhD 1983 Medicinal Chemistry University of Minnesota
• Postdoc 1985 Pharmacology University of Rochester

Overview

Adnan is interested in 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.

Work-Related Interests/Research:

Bioactivation: Insights into Toxicity and Anticancer Prodrug Design

Highlighted Publications:

• P.J. Sausen and A.A. Elfarra. Cysteine conjugate S-oxidase: Characterization of a novel enzymatic activity in rat hepatic and renal microsomes. J. Biol. Chem. 265, 6139-6145 (1990).
• R.J. Duescher and A.A. Elfarra. 1,3-Butadiene oxidation by human myeloperoxidase: Role of chloride ion in catalysis of divergent pathways. J. Biol. Chem., 267, 19859-19865 (1992).
• R. Duescher, M. Lawton, R. Philpot, and A. Elfarra. Flavin-containing monooxygenase (FMO)-dependent metabolism of methionine and evidence for FMO3 being the major FMO involved in methionine sulfoxidation in rabbit liver and kidney microsomes. J. Biol. Chem., 269, 17525-17530 (1994).
• R.R. Selzer and A.A. Elfarra. In vitro reactions of butadiene monoxide with single and double stranded DNA: Characterization and quantitation of several purine and pyrimidine adducts. Carcinogenesis, 20, 285-292 (1999).
• T.S. Moll, A.S. Harms, and A.A. Elfarra. A comprehensive structural analysis of hemoglobin adducts formed after in vitro exposure of erythrocytes to butadiene monoxide. Chem. Res. Toxicol., 13, 1103-1113 (2000).
• R.J. Krause, L.H. Lash, and A.A. Elfarra. Human kidney flavin-containing monooxygenases and their potential roles in cysteine S-conjugate metabolism and nephrotoxicity. J. Pharmacol. Exp. Ther., 304, 185-191 (2003).
• Xin-Yu Zhang and A.A. Elfarra. Characterization of 1,2,3,4-diepoxybutane-2'-deoxyguanosine cross-linking products formed at physiological and non-physiological conditions. Chem. Res. Toxicol., 19, 547-555 (2006).
• R.J. Krause, S.C. Glocke, A.R. Sicuri, S.L. Ripp and A.A. Elfarra. Oxidative metabolism of seleno-L-methionine to L-methionine selenoxide by flavin-containing monooxygenases. Chem. Res. Toxicol., 19, 1643-1649 (2006).
• B.I. Eklund, S. Gunnarsdottir, A.A. Elfarra, and B. Mannervik. Human glutathione transferases catalyzing the bioactivation of anticancer thiopurine prodrugs. Biochem. Pharmacol., 73, 1829-1841 (2007).
• A.A. Elfarra and R.J. Krause. 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., 321, 1095-1101 (2007).