The effects of ursodeoxycholic acid on sepsis-induced cholestasis management in an animal model

Abstract

Objectives: Cholestasis refers to a reduction in bile flow from the liver into the biliary system. Ursodeoxycholic acid (UDCA) is commonly used for the treatment of hepatic cholestasis. This study aimed to explore the role of UDCA in the treatment and prevention of lipopolysaccharide (LPS)-induced cholestasis. Methods: Sixty male albino rats were randomly classified into five groups of 12 rats each: the control group (received saline and water), UDCA group (received UDCA), LPS group (received LPS), treatment group (received LPS followed by UDCA), and prevention group (received UDCA followed by LPS). Changes in gamma-glutamyl transferase (GGT), plasma aspartate transferase (AST), plasma alkaline transferase (ALT), plasma alkaline phosphatase (ALP), total bilirubin (TBIL), hepatocyte apoptosis, immunomodulatory activity, plasma pro-inflammatory cytokines (TNF-α, IL-1α, and IL-4), and liver histology were assessed. Results: UDCA improved serum liver chemical markers (GGT, ALP, and AST) in both the prevention and treatment groups (p < 0.05 and p < 0.05, respectively). CD3 count was higher in the UDCA treatment group compared to the LPS group (p < 0.001). UDCA caused a reduction in plasma TNF-α in the prevention group (P < 0.05); however, it had no effect on the treatment group, as compared to the LPS group. Similarly, UDCA had no effect on IL-1α or IL-4. UDCA treatment resulted in improved liver histological features and a significant reduction in liver tissue apoptosis in both the treatment and prevention groups, as compared to the LPS group (p = 0.013 and p = .002, respectively). Conclusions: This study provides evidence of the effectiveness of UDCA for the treatment and prevention of sepsis-induced cholestasis.