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.