H. Vasken Aposhian,

Molecular mechanisms and treatment of heavy metal intoxication; theraputic chelating agents.

Research Activities

The major projects of our laboratory deal with the molecular mechanisms and treatment of heavy metal intoxication.  At present we are studying the molecular mechanisms by which arsenate and arsenite are detoxified in the mammalian body.  Also, we are studying the molecular mechanisms as to how the choroid plexus serves as a sink or filter for certain metals and thus protects the CSF and brain from toxic substances.  Our third major area of interest involves studying the pharmacological and toxicological properties of the new therapeutically useful chelating agents.

Publications (Query PubMed for this investigator)

Radabaugh, TR and Aposhian, HV:  Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase.  Chem. Res. Toxicol. 13(1):26-30, 2000.

Zakharyan, R.A. and Aposhian, H.V.:  Arsenite methylation by methylvitamin B12 and glutathione does not require an enzyme.  Toxicol. Appl. Pharmacol. 154:287-291, 1999.

Wildfang, E., Zakharyan, R.A., and Aposhian, H.V.:  Enzymatic methylation of arsenic compounds.  VI.  Characterization of hamster liver arsenite and methylarsonic acid methyltransferase activities in vitro.  Toxicol. Appl. Pharmacol. 152:366-375, 1998.

Gonzalez-Ramirez, D., Zuniga-Charles, M., Narro-Juarez, A., Molina-Recio, Y., Hurlbut, K.M., Dart, R.C., and Aposhian, H.V.:  DMPS (2,3-dimercaptopropane-1-sulfonate, dimaval) decreases the body burden of mercury in humans exposed to mercurous chloride.  J. Pharmacol. Exp. Ther. 287:8-12, 1998.

Healy, S.M., Zakharyan, R.A., and Aposhian, H.V.:  Enzymatic methylation of arsenic compounds: IV. In vitro and in vivo deficiency of the methylation of arsenite and monomethylarsonic acid in the guinea pig.  Mutat. Res. 386:229-339, 1997.

Aposhian, H.V., Arroyo, A., Cebrian, M.E., del-Razo, L.M., Hurlbut, K.M., Dart, R.C., Gonzalez-Ramirez, D., Kreppel, H., Speisky, H., Smith, A., Gonsebatt, M.E., Ostrosky-Wegman, P., and Aposhian, M.M.:  DMPS-arsenic challenge test. I: Increased urinary excretion of monomethylarsonic acid in humans given dimercaptopropane sulfonate.  J. Pharmacol. Exp. Ther. 282:192-200, 1997.

Aposhian, H.V.:  Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity.  Annu. Rev. Pharmacol. Toxicol. 37:397-419, 1997.

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