Assessment of animal wellbeing in bile duct ligation models

Cholestasis is one of the common causes of liver fibrosis and cirrhosis. The prevailing animal model currently used to study cholestasis is the common bile duct ligation (cBDL). A modification of this model is the ligation of the left hepatic bile duct (pBDL), which induces cholestasis only in the left liver lobe. We also simultaneously ligated the left bile duct with the corresponding left hepatic artery (pBDL+pAL). After induction of partial or total cholestasis in mice the wellbeing of these animals was evaluated by assessing burrowing behavior, body weight and a distress score. To compare pathological features of these animal models, the plasma levels of liver enzymes, necrotic areas within the liver tissue and fibrosis were assessed. The survival rate of the animals and the wellbeing was comparable between pBDL+pAL and pBDL. However, surgical intervention by pBDL+pAL caused confluent necrosis in contrast to the focal necrosis observed after pBDL. Interestingly, pBDL animals had a significantly higher survival rate and their wellbeing was significantly improved when compared to cBDL animals. On day 14 after ligation liver enzymes such as aspartate and alanine aminotransferase, alkaline phosphatase and glutamate dehydrogenase were significantly elevated after cBDL, but only glutamate dehydogenase activity was increased after pBDL. Importantly, pBDL reduced the number of mice needed and improved the wellbeing of animals. Therefore, the pBDL model might be useful for future studies when assessing local pathological features during cholestasis.