Fish omega-3 fatty acids induce liver fibrosis in the treatment of bile duct-ligated rats.

BACKGROUND: Biliary atresia-induced cholestasis increases hepatic oxidative stress with eventual progression to cirrhosis and liver failure. Omega-3 fatty acids play a possible role in the regulation of oxidative stress and the improvement of cholestasis. AIM: The goal of the present study is to investigate the role of dietary supplementation of fish omega-3 fatty acids in the reduction of hepatocellular damage by using a rat common bile duct ligation model. METHODS: Sprague-Dawley rats received either sham or bile duct ligation (BDL) and were divided into four study groups: Sham+saline (Sham+sal) group, Sham+Fish oil (Sham+FO) group, BDL+saline (BDL+sal) group, and BDL+Fish oil (BDL+FO) group. Rats from each group were assigned to receive, besides regular chow, once daily with either normal saline or fish omega-3 fatty acids (0.4 % of its own body weight) via gavage for 10 days. Samples of blood, liver tissue homogenates, and histological studies from different groups were analyzed at the end of the study. RESULTS: Rats from BDL+FO had significantly impaired liver function as compared to other study groups (p < 0.05 is of significant difference). Ishak scores and the TGF-b1 contents were significantly higher in rats that received BDL+FO, p < 0.05. Contrary to TGF-b1 liver content, rats from the BDL+FO group had the lowest glutathione levels among the study groups, p < 0.05. CONCLUSIONS: Fish omega-3 fatty acids supplementation, albeit increased tissue content of DHA, tended to increase liver fibrosis in BDL rats, decrease liver glutathione level, and compromise hepatic function; fish oil supplementation to subjects with biliary atresia might be of potential hazard and should be used with caution.

Reduced brain content of arachidonic acid and docosahexaenoic acid is related to the severity of liver fibrosis.

BACKGROUND: Cognitive deficiency noted post-liver transplantation might be a result of consequential metabolic derangement before liver transplantation. Long-chain polyunsaturated fatty acids, especially arachidonic acid (AA) and docosahexaenoic acid (DHA), affect the development of the central nervous system and its absorption is influenced by obstructive jaundice. AIM: To investigate the possible relationship between the brain content of AA and DHA with the severity of obstructive jaundice using a bile duct ligation rat model. METHODS: Sprague-Dawley rats were divided into three groups: Sham (n = 5): rats received sham operation on P17 (17 days after delivery) and were sacrificed on P31; BDL2w (n = 5): rats received bile duct ligation and were sacrificed on P31; BDL4w (n = 7): rats received bile duct ligation and were sacrificed on P45. Liver function test, histopathology, and fatty acid composition of the brain tissues were analyzed. RESULT: The Sham group had significantly lowered total/direct bilirubin level (0.6 + 0.1/0.3 + 0.1 mg/dl) as compared to the BDL2w group (3.8 + 1.5/1.6 + 1.0 mg/dl) and the BDL4w group (4.3 + 0.6/3.3 + 0.5 mg/dl) (P = 0.04 and 0.008, respectively). Liver fibrosis and inflammatory changes of hepatocytes increased from the Sham group, the BDL2w group, to the BDL4w group. The Sham group had significantly higher AA and DHA content. The brain content of AA and DHA correlated negatively to the duration of bile duct ligation, the total/direct bilirubin level, and the degree of liver fibrosis. CONCLUSION: Our results demonstrated that reduced AA and DHA content in the brain of rats which received bile duct ligation is closely related to both the severity of liver fibrosis and the impairment of liver function.