Hydrogen-rich saline protects against hepatic injury induced by ischemia-reperfusion and laparoscopic hepatectomy in swine

Hepatobiliary Pancreat Dis Int. 2019 Feb;18(1):48-61. doi: 10.1016/j.hbpd.2018.12.001. Epub 2018 Dec 6.

Abstract

Background: Hydrogen-rich saline (HRS) has antioxidative, anti-inflammatory and anti-apoptotic properties. We investigated the effects of hydrogen on hepatic ischemia-reperfusion (I/R) and laparoscopic hepatectomy in swine.

Methods: Twenty-one healthy Bama miniature pigs were randomly divided into the sham group, ischemia-reperfusion injury (IRI) group, HRS-5 (5 mL/kg) group, and HRS-10 (10 mL/kg) group. HRS was injected through the portal vein 10 min before reperfusion and at postoperative day 1, 2 and 3. The roles of HRS on oxidative stress, inflammatory response and liver regeneration were studied.

Results: Compared with the IRI group, HRS treatment attenuated oxidative stress by increasing catalase activity and reducing myeloperoxidase. White blood cells in the HRS-10 group were reduced compared with the IRI group (P < 0.01). In the HRS-10 group, interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha, C-reactive protein and cortisol were downregulated, whereas interleukin-10 was upregulated. In addition, HRS attenuated endothelial cell injury and promoted the secretion of angiogenic cytokines, including vascular endothelial growth factor, angiopoietin-1 and angiopoietin-2. HRS elevated the levels of hepatocyte growth factor, Cyclin D1, proliferating cell nuclear antigen, Ki-67 and reduced the secretion of transforming growth factor-beta.

Conclusions: HRS treatment may exert a protective effect against I/R and hepatectomy-induced hepatic damage by reducing oxidative stress, suppressing the inflammatory response and promoting liver regeneration.

Keywords: Hydrogen-rich saline; Inflammation; Ischemia-reperfusion; Laparoscopic hepatectomy; Oxidative stress; Regeneration.

MeSH terms

  • Angiogenic Proteins / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Catalase / metabolism
  • Cell Cycle Proteins / metabolism
  • Disease Models, Animal
  • Hepatectomy / adverse effects*
  • Hepatectomy / methods
  • Inflammation Mediators / metabolism
  • Laparoscopy / adverse effects*
  • Laparoscopy / methods
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Liver Diseases / prevention & control*
  • Liver Regeneration / drug effects
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Saline Solution / pharmacology*
  • Swine
  • Swine, Miniature
  • Time Factors

Substances

  • Angiogenic Proteins
  • Anti-Inflammatory Agents
  • Antioxidants
  • Cell Cycle Proteins
  • Inflammation Mediators
  • Saline Solution
  • Catalase
  • Peroxidase