OBJECTIVES: Intestinal failure-associated liver disease (IFALD) is a feared and life-threatening complication in neonates with intestinal failure (IF) receiving long-term total parenteral nutrition (TPN). This study aims to investigate the effect of exogenous secretin on liver pathology and hepatic function in a rat model of PN-associated liver disease (PNALD). METHODS: Male Sprague-Dawley rats underwent right jugular venous catheterization to receive 14-day continuous TPN therapy. All rats were allocated into 3 groups: the Control group (n = 8) did not have surgery or TPN and was fed standard rat chow ad libitum; the TPN group (n = 8) underwent catheter insertion and TPN treatment; and the TPN/S group (n = 8) also underwent catheter insertion, TPN treatment, and exogenous secretin treatment (2.5 nmol · kg · day) daily. Fourteen days after initial surgery, we collected the animals' liver and blood samples for further test. RESULTS: The TPN/S group had diminished direct bilirubin (TPN, 2.1 ± 0.7 μmol/L; TPN/S, 1.5 ± 0.2 μmol/L) and liver total bile acid levels (TPN, 144.5 ± 21.2 μmol/L; TPN/S, 123.4 ± 10.4 μmol/L) and improved histological outcomes compared with those in the TPN group. Exogenous secretin also enhanced the canalicular transporter (BSEP, 0.5-fold, P = 0.011) and inhibited the basolateral transporter (OSTA, -0.48-fold, P = 0.002; OSTB, -0.6-fold, P = 0.013) of liver bile acid. CONCLUSIONS: In this animal model of PNALD, secretin may improve cholestasis by enhancing canalicular transport, inhibiting the basolateral export of liver bile acid, and eventually decreasing the total bile acid level in the liver. Exogenous secretin treatment may potentially prevent and treat IFALD in IF patients relying on long-term TPN therapy.
OBJECTIVES:Intestinal failure-associated liver disease (IFALD) is a feared and life-threatening complication in neonates with intestinal failure (IF) receiving long-term total parenteral nutrition (TPN). This study aims to investigate the effect of exogenous secretin on liver pathology and hepatic function in a rat model of PN-associated liver disease (PNALD). METHODS: Male Sprague-Dawley rats underwent right jugular venous catheterization to receive 14-day continuous TPN therapy. All rats were allocated into 3 groups: the Control group (n = 8) did not have surgery or TPN and was fed standard rat chow ad libitum; the TPN group (n = 8) underwent catheter insertion and TPN treatment; and the TPN/S group (n = 8) also underwent catheter insertion, TPN treatment, and exogenous secretin treatment (2.5 nmol · kg · day) daily. Fourteen days after initial surgery, we collected the animals' liver and blood samples for further test. RESULTS: The TPN/S group had diminished direct bilirubin (TPN, 2.1 ± 0.7 μmol/L; TPN/S, 1.5 ± 0.2 μmol/L) and liver total bile acid levels (TPN, 144.5 ± 21.2 μmol/L; TPN/S, 123.4 ± 10.4 μmol/L) and improved histological outcomes compared with those in the TPN group. Exogenous secretin also enhanced the canalicular transporter (BSEP, 0.5-fold, P = 0.011) and inhibited the basolateral transporter (OSTA, -0.48-fold, P = 0.002; OSTB, -0.6-fold, P = 0.013) of liver bile acid. CONCLUSIONS: In this animal model of PNALD, secretin may improve cholestasis by enhancing canalicular transport, inhibiting the basolateral export of liver bile acid, and eventually decreasing the total bile acid level in the liver. Exogenous secretin treatment may potentially prevent and treat IFALD in IFpatients relying on long-term TPN therapy.