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.
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.
Authors: Nicole Lind Henriksen; Svend Høime Hansen; Matthew Domenic Lycas; Xiaoyu Pan; Thomas Eriksen; Lars Søndergaard Johansen; Richard R Sprenger; Christer Stenby Ejsing; Douglas G Burrin; Kerstin Skovgaard; Vibeke Brix Christensen; Thomas Thymann; Stanislava Pankratova Journal: Physiol Rep Date: 2022-07