Development of an Animal Model of Fibrous Cholangitis in Pigs

Abstract

ABSTRACTIntroduction: The aim of this study was to develop a model of fibrous cholangitis in the offspring of gravid domestic pigs through the administration of 1,4-phenylene diisothiocyanate (DITC). Material and Methods: Six young domestic pigs and two gravid pigs with their offspring (21 pigs) were used as experimental models and six wild-type animals were used as controls. All pigs were divided into five main groups and five subgroups, according to their developmental stage and time of exposure to DITC. The following histopathological characteristics were quantitatively evaluated on a scale of 0–5: ductal proliferation, periportal fibrosis, inflammatory infiltration, periductal fibrosis and edema, intraluminal fibrosis, duct wall thickening, epithelial apoptosis, and arterial hyperplasia/hypertrophy. Results: Statistically significant differences were observed for most of the histopathological markers between the group of pigs’ offspring that received DITC at early gestation and their control group. Moreover, the group of animals that were exposed to the agent at early gestation exhibited significant differences for all histopathological characteristics compared to the animals that were exposed at late gestation. On the other hand, no statistically significant differences were observed between the group of animals that received the agent at late gestation and their healthy controls. Conclusions: Administration of DITC to domestic pigs in early pregnancy may induce histopathological patterns of fibrous cholangitis to their offspring imitating biliary atresia. This model may provide insight to the pathogenesis of the obstructive cholangitis in pigs.