This chapter discusses the use of hepatocytes to study ethanol metabolism and hepatotoxicity. Alcoholic liver disease is a complex, multifactoral disease that normally requires many years of alcohol abuse to develop. The fact that alcoholic liver disease requires this long period to develop is most likely to be a consequence of the compensatory or adaptive responses of the liver, and the tremendous capacity of the liver to replace damaged cells or regenerate after toxic injury. These facts have made studies using laboratory animals difficult. In fact, there is no convenient animal model that exhibits the full spectrum of pathology associated with alcoholic liver disease. Hepatocytes isolated from the liver, rapidly dedifferentiate and lose the ability to metabolize ethanol. Because of this, until recently, it has not been possible to investigate the effects of prolonged ethanol metabolism in vitro. Using genetic engineering techniques, a number of recombinant, hepatic cell lines have been created that express the enzymes responsible for the metabolism of ethanol. Although the use of these cell lines has limitations, but many mechanistic studies have been completed that previously were difficult if not impossible to perform. Ethanol metabolism results in many physiologic changes in hepatocytes that occur simultaneously.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)