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 = 0.002, respectively). Conclusions This study provides evidence of the effectiveness of UDCA for the treatment and prevention of sepsis-induced cholestasis.

Impact of Ursodeoxycholic Acid in Critically Ill Patients With Sepsis: A Retrospective Study

“…28 Furthermore, it has also been reported that pre‐treatment with ursodeoxycholic acid protects against lung injury induced by fat embolism syndrome (FES) and improves FES-induced ARDS. 29,31 Taken together, this study further supports the potential beneficial role of UDCA as an attractive and safe adjunctive immunomodulatory therapy in sepsis as well as in other infectious and/or critical inflammatory illnesses, especially those with respiratory involvements.…”

“…18,27,28,30 In an animal-model study assessing the use of UDCA for treating and preventing sepsis-induced cholestasis, UDCA improved liver markers and significantly reduced liver apoptosis in both treatment and prevention groups. 29…”

“…18,27,28,30 In an animal-model study assessing the use of UDCA for treating and preventing sepsis-induced cholestasis, UDCA improved liver markers and significantly reduced liver apoptosis in both treatment and prevention groups. 29 Rina R. et al, in a small (n = 37) randomized double-blind controlled trial, investigated the effect of UDCA in the management of sepsis-associated cholestasis in neonates. The investigators concluded that UDCA improves laboratory parameters (total bilirubin, direct bilirubin, and AST levels); however, it was not statistically significant.…”

Pathophysiology of sepsis‐induced cholestasis: A review

“…52 Impairment of liver enzymes with hepatic histopathological changes as a response to sepsis. Sepsis may be associated with elevation of liver and biliary enzymes suggesting cholestasis: hyperbilirubinemia due to abnormal hepatic excretory function, 53 associated with increased alkaline phosphatase (ALP), 54,55 gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT). 54 On pathological specimens, bile acids have been noticed both in the bile ducts and in the liver cells cytoplasm.…”

Ursodeoxycholic and chenodeoxycholic bile acids attenuate systemic and liver inflammation induced by lipopolysaccharide in rats

“…The secondary bile acid, ursodeoxycholic acid (UDCA), generated through the conversion of the primary bile acid chenodeoxycholic acid (CDCA) in the gastrointestinal tract under the in uence of gut micro ora, offers a broad range of protective effects with minimal adverse effects [8]. In addition to studies highlighting cytoprotective and antiapoptotic effects [9,10], numerous investigations emphasized the remarkable anti-in ammatory [11][12][13], immunomodulatory [14,15], and antioxidant properties of UDCA [16,17]. UDCA has been shown to inhibit endothelial dysfunction by mitigating endoplasmic reticulum stress [18], reducing the production of reactive oxygen species (ROS) [18][19][20], preventing the release of various pro-in ammatory cytokines, promoting the secretion of antiin ammatory cytokines, and inhibiting the expression of nuclear factor κB (NF-κB) and inducible nitric oxide synthase (iNOS) induced by in ammation [20,21].…”