What is the pathogenesis of liver damage induced by ethanol?

They investigated the effects of ethanol on the IGF-I system with the involvement of JNK1/2 activity and ADH by using each chemical inhibitor in primary cultured rat hepatocytes. The results indicate that ethanol inducedp-JNK1/2 activation is associated with the IGF-I system and cell viability in hepatocytes. Furthermore, alcohol dehydrogenase is involved in the relationship between ethanol-induced inactivation of p-JNK1/2 and the changes of the IGF-I system and cell viability.

Body of text: Insulin-like growth factor (IGF)-I is a peptide that plays an important role in regulating metabolism, growth, and differentiation. Although the relationships between ethanol-induced cellular action and apoptosis via MAPK including JNK1/2 activity have been reported previously, the secretory mechanism by which the IGF-I system (IGF-I secretion, IGF-I mRNA expression, and IGF-IR activity) remains to be elucidated in primary cultured hepatocytes.

A research article to be published on January 28, 2008 in the World Journal of Gastroenterology addresses this question. Using Radioimmunoassay, RT-PCR, MTT assay, and Westernblotting, the authors investigates the relationship of IGF-I system and JNK1/2 as well as ADH activity by adding specific JNK1/2 and ADH inhibitor during ethanol exposure.

Their main findings are: (1) ethanol transiently increased p-JNK1/2 activity at 60 min and then decreased it at 180 min. (2) ethanol-induced transient activation of p-JNK1/2 increased in the IGF-I system, but this decreased when p-JNK1/2 was inactivated. Furthermore, IGF-IR activity also regulates ethanol-induced secretion and synthesis of IGF. (3) Cell viability is decreased via ADH by ethanol. These findings might be helpful to understand the pathogenesis of liver damage induced by ethanol, and may lead to a rational therapeutic intervention against ethanol toxicity.

Source: World Journal of Gastroenterology