A newborn rabbit model for total parenteral nutrition: effects of nutritional components on cholestasis

A newborn rabbit model for total parenteral nutrition (TPN) was developed to examine the effects of nutritional components on cholestasis. Thirty-five newborn Japanese white rabbits were divided into five groups. Rabbits in group I received glucose-based TPN solution, Group II received lipid-based solution, group III received larger amounts of amino acids than group I, and group IV received larger amounts of nonprotein calories than groups I and II. Rabbits in group V were given mother's milk freely. After the duration of TPN for 7 days, blood samples and liver were obtained when rabbits were killed. In group IV, the serum level of T-Bil (1.44 +/- 0.68 mg/dliter) was significantly higher than those in other groups (group I: 0.28 +/- 0.04 mg/dl; group II: 0.49 +/- 0.12 mg/dl; group III: 0.21 +/- 0.04 mg/dl; group V: 0.28 +/- 0.07 mg/dl), and serum level of GOT (44.2 +/- 25.2 units) and total bile acid (20.6 +/- 8.9 nmol/ml) were significantly higher than those in groups I, II, and III (group I: 16.8 +/- 7.8 units and 6.7 +/- 3.3 nmol/ml, group II: 21.5 +/- 7.9 units and 12.5 +/- 6.4 nmol/ml, group III: 14.3 +/- 4.2 units and 8.4 +/- 5.0 nmol/ml, respectively). Furthermore, there was histological cholestasis characterized by bile plugs in bile ducts, and bile pigments in Kupffer cells and hepatocytes, whereas there were no, or scarce findings of cholestasis in the other groups. These results indicate that an excessive administration of nonprotein calories in TPN contributes to the occurrence of cholestasis. In addition this animal model may be useful in investigating the etiology of cholestasis.