Robert A. Roth

rothr@msu.edu
Phone: (517) 353-9841
Home Department: Pharmacology & Toxicology
Home Page: Pharmacology & Toxicology

MSU Distinguished Professor, Assoc. Director, National Food Safety and Toxicology 

1975, Ph. D., The Johns Hopkins University
1975-77, Postdoctoral Fellow, Yale University

Research Synopsis:

Harmful Effects of the Inflammatory Response

Researchers in my laboratory are interested in inflammation as a determinant of susceptibility to the toxic effects of drugs and other chemical agents . All of us experience episodes of inflammation. We are interested in how modest inflammation can make individuals particularly sensitive to toxic chemicals. In rats, we create modest inflammation by administering a small dose of endotoxin (a bacterial product) that by itself is noninjurious. The modest inflammation markedly enhances liver injury caused by drugs and toxic chemicals. For example, aflatoxin B 1 is a toxic metabolite produced by a fungus that contaminates nuts and grains. We are exposed to small amounts of it when we eat products made from peanuts or corn, and it is of concern because it can cause liver damage and hepatic cancer in people and animals. We have found that a small dose of endotoxin that is without effect by itself markedly enhances the hepatotoxic effects of aflatoxin B 1 , as well as other toxic agents that occur in our food or environment. Thus, endotoxin exposure or underlying inflammation from other causes may be an important determinant of sensitivity of people and animals to toxic chemicals.

These findings have led us to a potentially important hypothesis that concurrent inflammation and its interaction with drugs may underlie some of the rare, idiosyncratic reactions people experience when they take certain drugs. In the laboratory, we are working to characterize this inflammation-induced augmentation of toxicity and to explore the cellular and molecular mechanisms that underlie it, with particular emphasis on the role of inflammatory factors such as neutrophils, cytokines and the hemostatic system.

Selected Publications

Review articles:

Roth, R.A., Luyendyk, J.P., Maddox, J.F. and Ganey, P.E. Inflammation and Drug Idiosyncrasy—Is There a Connection? J. Pharmacol. Exp. Ther., 307:1-8, 2003.

Ganey, P.E., Luyendyk, J.P., Maddox, J.F. and Roth, R.A. Adverse hepatic drug reactions: inflammatory episodes as consequence and contributor. Chemico-Biol. Interact. 150: 35-51, 2004.

Research Articles:

Luyendyk, J.P., Maddox, J.F., Cosma, G.N., Ganey, P.E., Cockerell, G.L. and Roth, R.A. Ranitidine treatment during a modest inflammatory response precipitates idiosyncrasy-like liver injury in rats. J. Pharmacol. Exp. Ther. 307:9-16, 2003.