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Jack A. Hinson, Ph.D.
Professor and Director, Division of Toxicology

Jack A. Hinson, Ph.D.
PHD
Vanderbilt University, 1972

Research Interests
Drug-induced liver toxicity is a significant problem in getting new drugs on the market. A major factor for this is that mechanisms of drug-induced liver toxicities are poorly understood. A significant focus of our laboratory is investigating mechanisms of liver toxicity (necrosis) produced by the commonly used analgesic/antipyretic drug acetaminophen. Acetaminophen is sold under a variety of trade names including TylenolŪ. Whereas the drug is safe at therapeutic doses, in overdose it can produce a liver toxicity leading to death. The toxicity is mediated by conversion of the drug to a metabolite that reacts with glutathione leading to its depletion and covalently binds to protein. We have shown that these events lead to oxidative/nitrosative stress causing mitochondrial dysfunction and subsequent necrosis. We are investigating mechanisms of how the reactive metabolite induces oxidative/nitrosative stress and how these events cause mitochondrial dysfunction and death of the cell.

E-mail
jahinson@uams.edu

Selected Publications
Reid, A.B., Kurten, R.C., McCullough, S.S., Brock, R.W., and Hinson, J.A. Mechanisms of acetaminophen-induced hepatotoxicity: role of oxidative stress and mitochondrial permeability transition in freshly isolated mouse hepatocytes. Journal of Pharmacology and Experimental Therapeutics 312:509-516, 2005.

Timothy J. Davern II, Laura P. James, Jack A. Hinson, Julie Polson, Anne M. Larson, Robert J. Fontana, Ezmina Lalani, Santiago Munoz, A. Obaid Shakil, William M. Lee and the Acute Liver Failure Study Group. Measurement of Serum Acetaminophen-Protein Adducts in Patients with Acute Liver Failure. Gastroenterology 130(3):687-694, 2006.

James, L.P., Donahower, B.C., Burke, A.S., McCullough, S., and Hinson, J.A. Induction of nuclear factor HIF1α in acetaminophen toxicity: Evidence for Oxidative Stress. Biochemical Biophysical Research Communications 343 (1):171-176, 2006.

Donahower, B. McCullough, S. S., Kurten, R. C., Lamps, L. W., Simpson, P. M. Hinson, J. A., and James, L. P Vascular Endothelial Growth Factor and Hepatocyte Regeneration in Acetaminophen Toxicity. American Journal of Physiology, Gastrointestinal Liver Physiology 291(1):G102-9, 2006.

James LP, Alonso EM, Hynan LS, Hinson JA, Davern TJ, Lee WM, Squires RH and the Pediatric Acute Liver Failure Study Group. Detection of Acetaminophen Protein Adducts in Children With Acute Liver Failure of Indeterminate Cause. Pediatrics 118(3):e676-e681, 2006.

Burke, AS. Redeker. K, Kurten, RC, James, LP, and Hinson, JA. Mechanisms of chloroform-induced hepatotoxicity: oxidative stress and mitochondrial permeability transition in freshly isolated mouse hepatocytes. Journal of Toxicology and Environmental Health, Part A 70:1936-1845, 2007.

James, LP, Roberts D, Simpson PM, Capparrelli E, Hinson JA, Davern T, Lee ,WM, Acute Liver Failure Study Group (NIDDK). Examination of Acetaminophen Protein Adducts in Adults with Acute Liver Failure: Pharmacokinetics and Clinical Comparisons. Pediatrics 84 (6):684-690, 2008.

James, L.P., Letzig, L., Simpson, P.M., Capparelli, E., Roberts, D.W., Hinson, J.A., Davern, T.J., and Lee, W.M. Pharmacokinetics of acetaminophen protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metabolism and Disposition 37:1779-1784, 2009.

Hinson, J.A., Roberts, D.R., and James, L.P. Mechanisms of Acetaminophen-Induced liver necrosis. Handbook of Experimental Pharmacology. In. Idiosyncratic Drug Toxicities. Editor Jack Uetrecht,. Springer, Berlin, 2009.

View Dr. Hinson's PubMed publication list.

University of Arkansas for Medical Sciences
Department of Pharmacology and Toxicology
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Little Rock, AR 72205
(501) 686-5510
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