3,5-diethoxycarbonyl-1,4-dihydrocollidine diet: A rodent model in cholestasis research

Abstract

Liver cholestasis is characterized by impairment in bile flow. Among cholestatic diseases, primary biliary cholangitis and primary sclerosing cholangitis represent relevant causes of chronic liver disease, associated to significant morbidity and mortality. To better understand and to address therapeutic strategies to cholangiopathies is essential to develop an in vivo model which recapitulates the pathological features of the disease. Chronic feeding of 3,5-diethoxycarbonyl-1,4-dihydrocollidine, named DDC, has been proposed as an in vivo model for cholestatic disease due to the formation of intraductal porphyrin plugs. Chronic feeding of DDC in mice reproduces the main histopathological hallmarks of human cholestatic disease such as (1) remodeling of biliary compartments giving rise to ductular reaction, (2) periductular fibrosis, and (3) inflammatory infiltrate. This chapter describes the materials and methods necessary for the development and characterization of DDC diet-based mouse model.