Description of Research Program Our research focuses at the role of free radicals in liver diseases, including hepatic hypoxia-reperfusion injury, primary graft failure after orthotopic liver transplantation, alcoholic and non-alcoholic hepatic steatosis, cholestasis and liver fibrosis. We use in vivo and in vitro models in combination with electron spin resonance, imaging cell biology and molecular biology techniques to delineate the pathways which lead to overproduction of reactive oxygen and nitrogen species and the effects of these reactive species in pathophysiology of liver diseases. In addition, we investigate the nephrotoxicity of immunosuppressive drugs such as cyclosporin A and tacrolimus. The goal of our research is to provide new insights into the mechanisms and to develop mechanism-based strategies to prevent and treat these hepatic and renal diseases. Selected Publications Zhong, Z., Connor, H.D., Froh, M., Lind, H., Bunzendahl, H., Mason, R.P., Thurman, R.G., and Lemasters, J.J. Free Radical-Dependent Dysfunction of Small-for-Size Rat Liver Grafts: Prevention by Plant Polyphenols. Gastroenterology 129:652-64. 2005. Zhong, Z., Connor, H.D., Froh, M., Bunzendahl, H., Mason, R.P., Thurman, R.G., and Lemasters, J.J. Polyphenols from Camellia sinenesis Prevent Primary Graft Failure after Transplantation of Ethanol-Induced Fatty Livers from Rats. FRBM 36:1248-58, 2004. Zhong, Z., Wheeler, M.D., Li, X.L., Froh M., Schemmer, P., Yin, M., Bunzendahl, H., Bradford, B.U., and Lemasters, J.J.: Glycine, a Novel Anti-Inflammatory, Immunomodulatory and Cytpoprotective Agent. Current Opinion in Clinical Nutrition and Metabolic Care 6:229-240, 2003. Zhong, Z., Froh, M., Wheeler, M.D., Lehmann. T., and Thurman, R.G. Viral Delivery of Superoxide Dismutase Gene Reduces Experimental Cholestasis-Induced Liver Injury in the Rat. Gene Therapy 9: 183-191, 2002. Zhong, Z., Connor, H.D., Yin, M., Moss, N., Mason R.P., Bunzendahl, H., Forman, D., and Thurman R.G. Dietary Glycine and Renal Denervation Prevents Cyclosporin A-Induced Hydroxyl Radical Production in the Rat Kidney. Mol. Pharm. 56: 455-463, 1999. |