Regulation of fibrogenesis during the early phase of common bile duct obstruction

Background: Both nitric oxide (NO) and prostaglandins have been proposed as inhibitor substances involved in collagen deposition in the hepatic parenchyma. The possible reciprocal connections between NO and eicosanoids in the development of liver fibrosis were investigated during the initial phase of common bile duct obstructions. Methods: A total of 30 male albino guinea pigs were randomly and equally assigned to three groups. Group 1 underwent sham laparotomy. Group 2 and group 3 were subjected to permanent common bile duct ligature for 24 and 72 h , respectively. Changes in the liver prostaglandin E-2 (PGE(2)), leukotriene C-4, malondialdehyde contents and plasma nitrite plus nitrate concentrations were measured. To evaluate the extent of hepatic fibrosis, histological assessment of liver was confirmed with the equivalent hydroxyproline contents of liver. Results: Twenty-four hours after ligature, the amount of malondialdehyde and PGE(2) and plasma nitrite plus nitrate concentrations increased significantly, whereas liver hydroxyproline contents did not change. However, 72 h after ligature (Group 3), lipid peroxidation and collagen deposition were significantly higher than that of the group 2 animals. The PGE(2) : leukotriene C-4 ratio peaked at 24 h and later decreased, whereas PGE(2) : NO ratio remained unchanged in both group 2 and group 3 animals. Conclusions: The initiation of collagen synthesis occurred in portal tract as early as within the first 72 h of bile duct obstruction. The optimum function of reactive oxygen species on the stellate cell activation might be determined by the interaction between NO and PGE(2).