Advertisement

Protective effects of hydrogen-rich saline on necrotizing enterocolitis in neonatal rats

  • Qingfeng Sheng
    Affiliations
    Department of General Surgery, Children's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine, Shanghai 200040, P. R. China

    Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute of Pediatric Research, Shanghai 200092, P. R. China
    Search for articles by this author
  • Zhibao Lv
    Correspondence
    Corresponding author. Tel.: +86 21 62790494; fax: +86 21 62790494.
    Affiliations
    Department of General Surgery, Children's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine, Shanghai 200040, P. R. China
    Search for articles by this author
  • Wei Cai
    Affiliations
    Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute of Pediatric Research, Shanghai 200092, P. R. China
    Search for articles by this author
  • Huanlei Song
    Affiliations
    Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute of Pediatric Research, Shanghai 200092, P. R. China
    Search for articles by this author
  • Linxi Qian
    Affiliations
    Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute of Pediatric Research, Shanghai 200092, P. R. China
    Search for articles by this author
  • Xueli Wang
    Affiliations
    Department of Pathology, Children's Hospital of Shanghai, Shanghai Jiaotong University School of Medicine, Shanghai 200040, P. R. China
    Search for articles by this author

      Abstract

      Purpose

      The aim of this study was to test the hypothesis that hydrogen-rich saline (HRS) might have protective effects on the development of necrotizing enterocolitis (NEC) in a neonatal rat model.

      Methods

      NEC was induced in male newborn Sprague–Dawley rats by formula feeding, exposure to asphyxia and cold stress. Sixty-four rat pups were divided randomly into four groups: C+NS (n=11), C+H2 (n=11), NEC+NS (n=20), and NEC+H2 (n=22). Rats in the former two groups were mother-fed. Pups received intra-peritoneal injection of HRS (10 ml/kg, 10 min before asphyxia stress twice a day) or the same dose of normal saline. Rats were monitored until 96 h after birth. Body weight, histological NEC score, survival time, malondialdehyde, antioxidant capacity, inflammatory mediators, and mucosal integrity were assessed.

      Results

      HRS treatment maintained the body weight, reduced the incidence of NEC from 85% (17/20) to 54.5% (12/22), increased the survival rate from 25% (5/20) to 68.2% (15/22), and attenuated the severity of NEC. In addition, HRS inhibited the mRNA expression of pro-inflammatory mediators (inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6), down-regulated lipid peroxidation, enhanced total antioxidant capacity, and prevented the increase of diamine oxidase in serum. However, no significant influence of HRS on the interleukin-10 mRNA expression was observed.

      Conclusions

      HRS showed beneficial effects on neonatal rats with NEC via decreasing oxidative stress, increasing antioxidant capacity, suppressing inflammation, and preserving mucosal integrity.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Pediatric Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lin P.W.
        • Stoll B.J.
        Necrotising enterocolitis.
        Lancet. 2006; 368: 1271-1283
        • Henry M.C.
        • Moss R.L.
        Necrotizing enterocolitis.
        Annu Rev Med. 2009; 60: 111-124
        • Neu J.
        • Walker W.A.
        Necrotizing enterocolitis.
        N Engl J Med. 2011; 364: 255-264
        • Lee J.W.
        • Davis J.M.
        Future applications of antioxidants in premature infants.
        Curr Opin Pediatr. 2011; 23: 161-166
        • Guven A.
        • Uysal B.
        • Gundogdu G.
        • et al.
        Melatonin ameliorates necrotizing enterocolitis in a neonatal rat model.
        J Pediatr Surg. 2011; 46: 2101-2107
        • Tayman C.
        • Tonbul A.
        • Kosus A.
        • et al.
        N-acetylcysteine may prevent severe intestinal damage in necrotizing enterocolitis.
        J Pediatr Surg. 2012; 47: 540-550
        • Ohsawa I.
        • Ishikawa M.
        • Takahashi K.
        • et al.
        Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals.
        Nat Med. 2007; 13: 688-694
        • Ohta S.
        Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases.
        Biochim Biophys Acta. 2012; 1820: 586-594
        • Buchholz B.M.
        • Kaczorowski D.J.
        • Sugimoto R.
        • et al.
        Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury.
        Am J Transplant. 2008; 8: 2015-2024
        • Buchholz B.M.
        • Masutani K.
        • Kawamura T.
        • et al.
        Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation.
        Transplantation. 2011; 92: 985-992
        • Caplan M.S.
        • Hedlund E.
        • Adler L.
        • et al.
        Role of asphyxia and feeding in a neonatal rat model of necrotizing enterocolitis.
        Pediatr Pathol. 1994; 14: 1017-1028
        • Mao Y.F.
        • Zheng X.F.
        • Cai J.M.
        • et al.
        Hydrogen-rich saline reduces lung injury induced by intestinal ischemia/reperfusion in rats.
        Biochem Biophys Res Commun. 2009; 381: 602-605
        • Schmittgen T.D.
        • Livak K.J.
        Analyzing real-time PCR data by the comparative CT method.
        Nat Protoc. 2008; 3: 1101-1108
        • Ohkawa H.
        • Ohishi N.
        • Yagi K.
        Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.
        Anal Biochem. 1979; 95: 351-358
        • Benzie I.F.
        • Strain J.J.
        The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power ": the FRAP assay.
        Anal Biochem. 1996; 239: 70-76
        • Luk G.D.
        • Bayless T.M.
        • Baylin S.B.
        Diamine oxidase (histaminase). A circulating marker for rat intestinal mucosal maturation and integrity.
        J Clin Invest. 1980; 66: 66-70
        • Morowitz M.J.
        • Poroyko V.
        • Caplan M.
        • et al.
        Redefining the role of intestinal microbes in the pathogenesis of necrotizing enterocolitis.
        Pediatrics. 2010; 125: 777-785
        • Weitkamp J.H.
        • Koyama T.
        • Rock M.T.
        • et al.
        Necrotising enterocolitis is characterised by disrupted immune regulation and diminished mucosal regulatory (FOXP3)/effector (CD4, CD8) T cell ratios.
        Gut. 2013; 62: 73-82
        • Saugstad O.D.
        Oxidative stress in the newborn—a 30-year perspective.
        Biol Neonate. 2005; 88: 228-236
        • Whitehouse J.S.
        • Xu H.
        • Shi Y.
        • et al.
        Mesenteric nitric oxide and superoxide production in experimental necrotizing enterocolitis.
        J Surg Res. 2010; 161: 1-8
        • Aydemir C.
        • Dilli D.
        • Uras N.
        • et al.
        Total oxidant status and oxidative stress are increased in infants with necrotizing enterocolitis.
        J Pediatr Surg. 2011; 46: 2096-2100
        • Cardinal J.S.
        • Zhan J.
        • Wang Y.
        • et al.
        Oral hydrogen water prevents chronic allograft nephropathy in rats.
        Kidney Int. 2010; 77: 101-109
        • Sun H.
        • Chen L.
        • Zhou W.
        • et al.
        The protective role of hydrogen-rich saline in experimental liver injury in mice.
        J Hepatol. 2011; 54: 471-480
        • Nadler E.P.
        • Stanford A.
        • Zhang X.R.
        • et al.
        Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: interleukin-11 mRNA expression inversely correlates with extent of disease.
        J Pediatr Surg. 2001; 36: 1122-1129
        • Caplan M.S.
        • Simon D.
        • Jilling T.
        The role of PAF, TLR, and the inflammatory response in neonatal necrotizing enterocolitis.
        Semin Pediatr Surg. 2005; 14: 145-151
        • Frost B.L.
        • Jilling T.
        • Caplan M.S.
        The importance of pro-inflammatory signaling in neonatal necrotizing enterocolitis.
        Semin Perinatol. 2008; 32: 100-106
        • Afrazi A.
        • Sodhi C.P.
        • Richardson W.
        • et al.
        New insights into the pathogenesis and treatment of necrotizing enterocolitis: Toll-like receptors and beyond.
        Pediatr Res. 2011; 69: 183-188
        • Xie K.
        • Yu Y.
        • Pei Y.
        • et al.
        Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release.
        Shock. 2010; 34: 90-97
        • Emami C.N.
        • Chokshi N.
        • Wang J.
        • et al.
        Role of interleukin-10 in the pathogenesis of necrotizing enterocolitis.
        Am J Surg. 2012; 203: 428-435
        • Anand R.J.
        • Leaphart C.L.
        • Mollen K.P.
        • et al.
        The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis.
        Shock. 2007; 27: 124-133
        • Xie K.
        • Yu Y.
        • Zhang Z.
        • et al.
        Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model.
        Shock. 2010; 34: 495-501
        • Guven A.
        • Gundogdu G.
        • Uysal B.
        • et al.
        Hyperbaric oxygen therapy reduces the severity of necrotizing enterocolitis in a neonatal rat model.
        J Pediatr Surg. 2009; 44: 534-540
        • Guven A.
        • Gundogdu G.
        • Vurucu S.
        • et al.
        Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats.
        J Pediatr Surg. 2009; 44: 1730-1735
        • Nakao A.
        • Toyoda Y.
        • Sharma P.
        • et al.
        Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study.
        J Clin Biochem Nutr. 2010; 46: 140-149