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Pre- and postnatal 1,4-phenylene di-isothiocyanate treatment does not induce bile duct injury in neonatal pigs
Insights
Researchers investigated if 1,4-phenylene di-isothiocyanate (DITC) could induce bile duct injury in pigs. The study found that DITC administration did not cause liver damage or biliary atresia (BA) in neonatal pigs.
Area of Science:
- Hepatology
- Toxicology
- Pediatric Gastroenterology
Background:
- Biliary atresia (BA) is a leading cause of pediatric liver transplants with unknown etiology.
- Current surgical treatments for BA have a high failure rate, highlighting the need for better understanding and models.
- Lack of suitable animal models hinders progress in BA research.
Purpose of the Study:
- To determine if pre and postnatal exposure to 1,4-phenylene di-isothiocyanate (DITC) can induce bile duct injury and cholestasis in neonatal pigs.
- To evaluate DITC as a potential agent for creating an animal model of biliary injury.
Main Methods:
- Pregnant sows were administered DITC at various doses and frequencies during gestation.
- Cesarean-delivered piglets received DITC postnatally or served as controls.
- Piglets were monitored for liver injury markers, and tissues were analyzed histopathologically.
Main Results:
- Piglets from sows exposed to DITC for 11 weeks exhibited reduced body weight and transient increases in gamma-glutamyl transferase.
- Histological analysis did not reveal signs of BA in any piglets.
- Elevated hepatic bile acids were observed in piglets from sows treated for 11 weeks, but serum bile acids remained unchanged.
Conclusions:
- Pre and postnatal administration of DITC to sows and piglets did not successfully induce bile duct injury or cholestasis.
- DITC is not a suitable agent for modeling biliary atresia in this piglet model.
- Further research is needed to develop effective animal models for biliary atresia.
Background:
Biliary 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.
Objective:
The 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.
Methods:
Pregnant 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.
Results:
Piglets 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).
Conclusions:
The administration of DITC to pregnant sows and neonatal piglets did not result in the development of bile duct or hepatic injury.
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