Advertisement

The Effects of Hydrogen-Rich Saline on the Contractile and Structural Changes of Intestine Induced by Ischemia-Reperfusion in Rats

  • Author Footnotes
    2 These three authors contributed equally to this work.
    Han Chen
    Footnotes
    2 These three authors contributed equally to this work.
    Affiliations
    Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Author Footnotes
    2 These three authors contributed equally to this work.
    Yan Ping Sun
    Footnotes
    2 These three authors contributed equally to this work.
    Affiliations
    Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Author Footnotes
    2 These three authors contributed equally to this work.
    Ping Fang Hu
    Footnotes
    2 These three authors contributed equally to this work.
    Affiliations
    Department of Gastroenterology, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Wen Wu Liu
    Affiliations
    Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Hong Gang Xiang
    Affiliations
    Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Yang Li
    Affiliations
    Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Rong Lin Yan
    Affiliations
    Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Ning Su
    Affiliations
    Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Can Ping Ruan
    Affiliations
    Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Xue Jun Sun
    Correspondence
    To whom correspondence and reprint requests should be addressed at Department of General Surgery, Shanghai Chang Zheng Hospital (Q.W.), and Department of Diving Medicine, Faculty of Naval Medicine (X.J.S.), Second Military Medical University, 415 Feng Yang Road, Shanghai, PR China.
    Affiliations
    Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Qiang Wang
    Correspondence
    To whom correspondence and reprint requests should be addressed at Department of General Surgery, Shanghai Chang Zheng Hospital (Q.W.), and Department of Diving Medicine, Faculty of Naval Medicine (X.J.S.), Second Military Medical University, 415 Feng Yang Road, Shanghai, PR China.
    Affiliations
    Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, PR China
    Search for articles by this author
  • Author Footnotes
    2 These three authors contributed equally to this work.
Published:August 28, 2009DOI:https://doi.org/10.1016/j.jss.2009.07.045

      Background

      Hydrogen has been considered as a novel antioxidant that prevents injuries resulted from ischemia-reperfusion (I/R) injury in various tissues. The study was designed to determine the effect of hydrogen-rich saline on the smooth muscle contractile response to KCl, and on epithelial proliferation and apoptosis of intestine subjected to I/R.

      Methods

      Intestinal I/R injury was induced in Sprague-Dawley rats using bulldog clamps in superior mesenteric artery by 45 min ischemia followed by 1 h reperfusion. Rats were divided randomly into four groups: sham-operated, I/R, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment groups. Hydrogen-rich saline (>0.6 mM, 6 mL/kg) or saline (6 mL/kg) was administered, respectively, via tail vein 30 min prior to reperfusion. Following reperfusion, segments of terminal jejunum were rapidly taken and transferred into isolated organ bath and responses to KCl were recorded. Samples of terminal jejunum were also taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in intestinal epithelium was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression and distribution of proliferating cell nuclear antigen (PCNA) were detected with immunohistochemistry.

      Results

      Hydrogen-rich saline treatment significantly attenuated the severity of intestinal I/R injury, with inhibiting of I/R-induced apoptosis, and promoting enterocytes proliferation. Moreover, Hydrogen-rich saline treatment significantly limited the neutrophil infiltration, lipid oxidation, and ameliorated the decreased contractility response to KCl in the intestine subjected to I/R.

      Conclusions

      These results suggest that hydrogen treatment has a protective effect against intestinal contractile dysfunction and damage induced by intestinal I/R. This protective effect is possibly due to its ability to inhibit I/R-induced oxidative stress, apoptosis, and to promote epithelial cell proliferation.

      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 Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Collard C.D.
        • Gelman S.
        Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury.
        Anesthesiology. 2001; 94: 1133
        • Cicalese L.
        • Sileri P.
        • Green M.
        • et al.
        Bacterial translocation in clinical intestinal transplantation.
        Transplantation. 2001; 71: 1414
        • Cerqueira N.F.
        • Hussni C.A.
        • Yoshida W.B.
        Pathophysiology of mesenteric ischemia/reperfusion: A review.
        Acta Cir Bras. 2005; 20: 336
        • Linfert D.
        • Chowdhry T.
        • Rabb H.
        Lymphocytes and ischemia-reperfusion injury.
        Transplant Rev (Orlando). 2009; 23: 1
        • Ballabeni V.
        • Barocelli E.
        • Bertoni S.
        • et al.
        Alterations of intestinal motor responsiveness in a model of mild mesenteric ischemia/reperfusion in rats.
        Life Sci. 2002; 71: 2025
        • Ozacmak V.H.
        • Sayan H.
        • Arslan S.O.
        • et al.
        Protective effect of melatonin on contractile activity and oxidative injury induced by ischemia and reperfusion of rat ileum.
        Life Sci. 2005; 76: 1575
        • Hassoun H.T.
        • Weisbrodt N.W.
        • Mercer D.W.
        • et al.
        Inducible nitric oxide synthase mediates gut ischemia/reperfusion-induced ileus only after severe insults.
        J Surg Res. 2001; 97: 150
        • Noda T.
        • Iwakiri R.
        • Fujimoto K.
        • et al.
        Programmed cell death induced by ischemia-reperfusion in rat intestinal mucosa.
        Am J Physiol. 1998; 274: G270
        • Wood K.C.
        • Gladwin M.T.
        The hydrogen highway to reperfusion therapy.
        Nat Med. 2007; 13: 673
        • McCord J.M.
        Oxygen-derived free radicals in postischemic tissue injury.
        N Engl J Med. 1985; 312: 159
        • 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
        • Gharib B.
        • Hanna S.
        • Abdallahi O.M.
        • et al.
        Anti-inflammatory properties of molecular hydrogen: Investigation on parasite-induced liver inflammation.
        C R Acad Sci III. 2001; 324: 719
        • Ohsawa I.
        • Nishimaki K.
        • Yamagata K.
        • et al.
        Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice.
        Biochem Biophys Res Commun. 2008; 377: 1195
        • Hayashida K.
        • Sano M.
        • Ohsawa I.
        • et al.
        Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury.
        Biochem Biophys Res Commun. 2008; 373: 30
        • 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
        • Zheng X.
        • Mao Y.
        • Cai J.
        • et al.
        Hydrogen-rich saline protects against intestinal ischemia/reperfusion injury in rats.
        Free Radic Res. 2009; 43: 478
        • 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
        • Cai J.
        • Kang Z.
        • Liu K.
        • et al.
        Neuroprotective effects of hydrogen saline in neonatal hypoxia-ischemia rat model.
        Brain Res. 2009; 1256: 129
        • Guneli E.
        • Cavdar Z.
        • Islekel H.
        • et al.
        Erythropoietin protects the intestine against ischemia/ reperfusion injury in rats.
        Mol Med. 2007; 13: 509
        • Mendoza J.
        • Chang C.Y.
        • Blalock C.L.
        • et al.
        Contractile function of the mechanically lengthened intestine.
        J Surg Res. 2006; 136: 8
        • Ohkawa H.
        • Ohishi N.
        • Yagi K.
        Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.
        Anal Biochem. 1979; 95: 351
        • Fu X.
        • Sheng Z.
        • Wang Y.
        • et al.
        Basic fibroblast growth factor reduces the gut and liver morphologic and functional injuries after ischemia and reperfusion.
        J Trauma. 1997; 42: 1080
        • Itoh H.
        • Yagi M.
        • Fushida S.
        • et al.
        Activation of immediate early gene, c-fos, and c-jun in the rat small intestine after ischemia/reperfusion.
        Transplantation. 2000; 69: 598
        • Chen W.
        • Fu X.B.
        • Ge S.L.
        • et al.
        Acid fibroblast growth factor reduces rat intestinal mucosal damage caused by ischemia-reperfusion insult.
        World J Gastroenterol. 2005; 11: 6477
        • Schoenberg M.H.
        • Beger H.G.
        Reperfusion injury after intestinal ischemia.
        Crit Care Med. 1993; 21: 1376
        • Mallick I.H.
        • Yang W.
        • Winslet M.C.
        • et al.
        Ischemia-reperfusion injury of the intestine and protective strategies against injury.
        Dig Dis Sci. 2004; 49: 1359
        • Valko M.
        • Leibfritz D.
        • Moncol J.
        • et al.
        Free radicals and antioxidants in normal physiological functions and human disease.
        Int J Biochem Cell Biol. 2007; 39: 44
        • Dedon P.C.
        • Tannenbaum S.R.
        Reactive nitrogen species in the chemical biology of inflammation.
        Arch Biochem Biophys. 2004; 423: 12
        • Cuzzocrea S.
        • Mazzon E.
        • Dugo L.
        • et al.
        Protective effects of a new stable, highly active SOD mimetic, M40401 in splanchnic artery occlusion and reperfusion.
        Br J Pharmacol. 2001; 132: 19
        • Balogh N.
        • Krausz F.
        • Levai P.
        • et al.
        Effect of deferoxamine and L-arginine treatment on lipid peroxidation in an intestinal ischemia-reperfusion model in rats.
        Acta Vet Hung. 2002; 50: 343
        • Yamaguchi T.
        • Dayton C.
        • Shigematsu T.
        • et al.
        Preconditioning with ethanol prevents postischemic leukocyte-endothelial cell adhesive interactions.
        Am J Physiol Heart Circ Physiol. 2002; 283: H1019
        • Nagata K.
        • Nakashima-Kamimura N.
        • Mikami T.
        • et al.
        Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice.
        Neuropsychopharmacology. 2009; 34: 501
        • Sato Y.
        • Kajiyama S.
        • Amano A.
        • et al.
        Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice.
        Biochem Biophys Res Commun. 2008; 375: 346
        • Kajiyama S.
        • Hasegawa G.
        • Asano M.
        • et al.
        Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance.
        Nutr Res. 2008; 28: 137
        • Prasad R.
        • Alavi K.
        • Schwartz M.Z.
        Glucagonlike peptide-2 analogue enhances intestinal mucosal mass and absorptive function after ischemia-reperfusion injury.
        J Pediatr Surg. 2000; 35: 1537
        • Sileri P.
        • Morini S.
        • Schena S.
        • et al.
        Intestinal ischemia/reperfusion injury produces chronic abnormalities of absorptive function.
        Transplant Proc. 2002; 34: 984