Pre- and postnatal 1,4-phenylene di-isothiocyanate treatment does not induce bile duct injury in neonatal pigs

Abstract

BackgroundBiliary atresia (BA) is the leading cause of pediatric liver transplants, however; the cause of biliary atresia (BA) is unknown. Furthermore, the most common treatment for this disease is with a surgical procedure, which has a greater than 50% failure rate after 5 years. Due to a lack of proper animal models to study the pathology of the disease, little progress has been made in the field. ObjectiveThe objective of this study was to test whether pre and postnatal 1,4-phenylene di-isothiocyanate (DITC) would induce bile duct injury and cholestasis in neonatal pigs. MethodsPregnant sows received DITC once at gestation week 5 (100 mg/kg; n=2), or 3 times at gestation weeks 5, 6, and 7 (100 mg/kg each; n=2), or twice per week at gestation weeks 5-16 (15 mg/kg each; n=2). Cesarian-delivered piglets of the sows were randomly assigned to receive approximately 200 mg/kg DITC on days two, four, and six of life or to remain untreated. Piglets were fed enterally and collected blood samples were monitored for markers of liver injury for 14 days. At the end of 14 days, tissues were weighed and collected for immunohistochemistry and histopathology scoring. ResultsPiglets from sows that received DITC for 11 weeks had lower (P < 0.05) final body weight and daily gain compared to other treatments. Piglets from sows that received DITC for 11 weeks had a transient increase in gamma-glutamyl transferase. Liver histological scoring and analysis also did not show signs of BA. Piglets that received DITC from 11-week DITC-treated sows had elevated hepatic bile acids (P < 0.05), but there was no difference in serum bile acids (P > 0.05). ConclusionsThe administration of DITC to pregnant sows and neonatal piglets did not result in the development of bile duct or hepatic injury.