A novel liver-targeted nitric oxide donor UDCA-Thr-NO protects against cirrhosis and portal hypertension.

Portal hypertension (PHT) is a common liver disease that is closely related to cirrhosis and has a high morbidity and mortality. The present study aimed to probe the efficacy of a novel nitric oxide (NO)-releasing agent with NO linked to ursodeoxycholic acid (UDCA) through threonine (UDCA-Thr-NO) as a liver-targeted therapy for cirrhosis and PHT. After intraperitoneal treatment of dimethyl nitrosamine-induced cirrhotic rats for 3 or 4 weeks, UDCA-Thr-NO could prevent ascites formation and reduce portal pressure instead of carotid artery pressure, when compared with UDCA or compound embryonic bovine liver extract tablets. Biochemical analysis of the rat sera also revealed that UDCA-Thr-NO improved the levels of alanine aminotransferase and total bilirubin and reduced the level of hydroxyproline (P < 0.05). Colorimetric analysis of the liver tissue by staining hematoxylin-eosin (HE) and Sirius red (SR) showed that UDCA-Thr-NO could improve pathological changes and reduce liver collagen deposition and intrahepatic resistance without affecting systemic circulation. It was concluded that UDCA-Thr-NO had a protective effect on liver injury and could be utilized to improve cirrhosis and PHT.