Urea Transporter Inhibitor 25a Reduces Ascites in Cirrhotic Rats

Ascites is a typical symptom of liver cirrhosis that is caused by a variety of liver diseases. Ascites severely affects the life quality of patients and needs long-term treatment. 25a is a specific urea transporter inhibitor with a diuretic effect that does not disturb the electrolyte balance. In this study, we aimed to determine the therapeutic effect of 25a on ascites with a dimethylnitrosamine (DMN)-induced cirrhotic rat model. It was found that 100 mg/kg of 25a significantly increased the daily urine output by 60% to 97% and reduced the daily abdominal circumference change by 220% to 260% in cirrhotic rats with a water intake limitation. The 25a treatment kept the serum electrolyte levels within normal ranges in cirrhotic rats. The H&E and Masson staining of liver tissue showed that 25a did not change the cirrhotic degree. A serum biochemical examination showed that 25a did not improve the liver function in cirrhotic rats. A Western blot analysis showed that 25a did not change the expression of fibrosis-related marker protein alpha-SMA, but significantly decreased the expressions of type I collagen in the liver of cirrhotic rats, indicating that 25a did not reverse cirrhosis, but could slow the cirrhotic progression. These data indicated that 25a significantly reduced ascites via diuresis without an electrolyte imbalance in cirrhotic rats. Our study provides a proof of concept that urea transporter inhibitors might be developed as novel diuretics to treat cirrhotic ascites.

Automated summary

In this study, 25a was found to significantly increase urine output and decrease abdominal circumference in cirrhotic rats without disturbing electrolyte balance. It also reduced the expression of type I collagen in the liver, indicating a potential to slow the progression of cirrhosis. These findings suggest that 25a may serve as a novel diuretic for treating cirrhotic ascites.