Abstract

IntroductionLiver regeneration is an exceptionally complex process, orchestrated by a multitude of growth factors and cytokines. Tumor necrosis factor-alpha (TNF-a) and interleukin-6 (Il-6) have a pivotal role in the initiation of the regenerative response. Ursodeoxycholic acid (UDCA) exhibits a liver protective effect that enhances liver growth after injury. The aim of the present study is to evaluate the effect of UDCA in the circulating levels of TNF-a and Il-6 in rats undergoing extended 80% hepatectomy.Materials and methodsTwenty-two male Sprague Dawley rats were randomly assigned in an experimental (UDCA group) and a control group. Mice in the UDCA-group received oral pretreatment of UDCA for two weeks preoperatively at a dosage of 25 mg/kg/day. An 80% hepatic resection was performed in both groups by resecting the middle, inferior right, and left lateral liver lobes. The experiment ended 48 hours postoperatively.ResultsUDCA pretreatment significantly depressed circulating levels of both TNF-a and Il-6 after the conclusion of the experiment as compared to the control group (p=0.001 and p=0.01, respectively). Furthermore, TNF-a levels were significantly reduced before the institution of liver injury (p=0.02). Mice in the UDCA-group exhibited better liver growth as demonstrated by significantly increased Ki-67 and mitotic rate (p=0.04 and p=0.02, respectively). Finally, the liver regeneration rate (LRR) was significantly elevated in the experimental group (UDCA group, 54.5% vs control group, 35.8%; p=0.002) signifying enhanced liver growth kinetics.ConclusionUDCA reduces the expression of TNF-a and Il-6 during the priming phase of liver regeneration. An 80% hepatectomy model of acute liver failure exhibited enhanced liver regeneration in the experimental group, plausibly due to the immunomodulatory effects of UDCA.

Highlights

  • Liver regeneration is an exceptionally complex process, orchestrated by a multitude of growth factors and cytokines

  • Tumor necrosis factor-alpha (TNF-a) levels were significantly reduced before the institution of liver injury (p=0.02)

  • Following on from the previous report by Uzun et al demonstrating the effectiveness of Ursodeoxycholic acid (UDCA) in a nonalcoholic fatty liver disease model, the aim of the present study is to further evaluate whether oral pretreatment with UDCA impacts the expression of TNF-a and Il-6 after extended hepatectomy and elucidate the potential role of UDCA in enhancing the liver regenerative process by regulating the post hepatectomy immune response [11]

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Summary

Objectives

The aim of the present study is to evaluate the effect of UDCA in the circulating levels of TNF-a and Il-6 in rats undergoing extended 80% hepatectomy. Following on from the previous report by Uzun et al demonstrating the effectiveness of UDCA in a nonalcoholic fatty liver disease model, the aim of the present study is to further evaluate whether oral pretreatment with UDCA impacts the expression of TNF-a and Il-6 after extended hepatectomy and elucidate the potential role of UDCA in enhancing the liver regenerative process by regulating the post hepatectomy immune response [11]

Methods
Results
Conclusion

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