title: Lactulose accelerates liver regeneration in rats by inducing hydrogen.
abstract: BACKGROUND
  Oxidative stress and inflammation are implicated in the process of liver regeneration. Lactulose orally administered can be bacterially fermented and induces dramatic amounts of endogenous hydrogen. Hydrogen has been confirmed to have antioxidant and anti-inflammatory properties. This study investigated the potential influence of lactulose administration on liver regeneration.
  
  
  METHODS
  Antibiotics were used to suppress bacterial fermentation of lactulose, and hydrogen-rich saline was used as a supplementary measure of exogenous hydrogen. The liver regeneration model was produced in Sprague-Dawley rats through 70% partial hepatectomy.
  
  
  RESULTS
  Compared with non-lactulose-treated group, lactulose administration remarkably increased the weights of remnant liver and inhibited increases in serum levels of transaminases more notably. In the lactulose-treated group, increases of markers for regeneration, such as proliferating cell nuclear antigen and cyclin D1, were highly elevated. Biochemically, lactulose administration increased liver superoxide dismutase activity and decreased malondialdehyde content. In the lactulose-treated group, excessive increases in inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, were inhibited significantly. Increased heme oxygenase-1 and superoxide dismutase 2 expression were also observed after lactulose treatment. The antibiotics suppressed the regeneration-promoting effect of lactulose by reducing hydrogen production, whereas supplementing hydrogen by hydrogen-rich saline would get a similar regeneration-promoting effect as lactulose administration.
  
  
  CONCLUSIONS
  Lactulose administration accelerates posthepatectomized liver regeneration in rats by inducing hydrogen, which may result from attenuation of the oxidative stress response and excessive inflammatory response.
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Rehabilitation, Heilongjiang Agricultural Reclamation General Hospital, Harbin, China.
authors.forename: Rongguo
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Xinxian
authors.initials: X
authors.lastname: Ruan
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Peitu
authors.initials: P
authors.lastname: Ren
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China. Electronic address: sygd_lbc@126.com.
authors.forename: Baochun
authors.initials: B
authors.lastname: Lu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006498:Hepatectomy; D006859:Hydrogen / Q000378:metabolism*; D007792:Lactulose / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D000637:Transaminases / Q000097:blood; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D005765:Gastrointestinal Agents; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D007792:Lactulose; D006859:Hydrogen; D000637:Transaminases
keywords: Inflammatory response; Lactulose; Liver regeneration; Oxidative stress response