Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat.

Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its parallel plasma and liver changes in levels of cytokines and nitric oxide (NO), involved in liver damage, remain unknown. The aims of this work were to quantify both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28 days after bile BDL, and to analyze their relationship with liver damage markers. One group of male Wistar rats was bile duct ligated and another group was sham operated, both groups were sacrificed 28 days after BDL. Plasma and liver cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, -1beta, -10 (IL-6, -1beta, -10) and interferon-gamma (IFN-gamma), were measured by ELISA. Plasma and hepatic NO was determined as NO(2)(-)+NO(3)(-) by an enzymatic method. Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase and bilirubins were determined in plasma. Collagen, lipid peroxidation and glycogen were quantified in liver. Two histopathological staining techniques were performed. BDL-induced cirrhosis was corroborated by the elevated liver damage markers and histopathological analysis. Chronic BDL significantly increased (P<0.05) most of plasma and hepatic cytokine levels and diminished the hepatic IFN-gamma amount. NO was increased in both tissues, but such change was only significant in plasma. Biliary cirrhosis produces interesting changes in plasma and hepatic levels of cytokines and NO. This finding in chronic BDL model in rats has not been previously described in both tissues for such cytokines and NO. Cytokines and NO imbalance favor establishment and perpetuation of cirrhosis.