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Original communication| Volume 137, ISSUE 1, P48-55, January 2005

Surgical manipulation of the intestine and distant organ damage—protection by oral glutamine supplementation

      Background

      The intestine is increasingly recognized as a primary effector of distant organ damage, such as the lung, after any abdominal surgery. Earlier studies have shown that surgical manipulation of the intestine induces generation of reactive oxygen species in the intestine, resulting in mucosal and lung damage. Because glutamine is preferentially used by the small intestine as an energy source, this study examined the effect of glutamine and glutamic acid on intestinal and lung damage after surgical manipulation.

      Methods

      Controls and rats were pretreated for 7 days with 2% glutamine or glutamic acid, or the isonitrogenous amino acids glycine or alanine in the diet and subjected to surgical manipulation of the intestine. The intestine and lung were assessed for damage, and protection offered by various amino acids was studied.

      Results

      Surgical manipulation resulted in oxidative stress in the intestine as evidenced by increased xanthine oxidase activity and decreased antioxidant status. Enterocyte mitochondria were also functionally impaired with altered calcium flux, decreased respiratory control ratio, and increased swelling. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by an increase in myeloperoxidase activity, lipid peroxidation, and antioxidant status. Glutamine or glutamic acid supplementation for 7 days before surgical manipulation showed a protective effect against the intestinal and lung damage.

      Conclusions

      This study suggests that preoperative enteral glutamine or glutamic acid supplementation attenuates intestinal and lung damage in rats during surgical manipulation and that this effect might offer protection from postsurgical complications.
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      References

        • Deitch E.A.
        Multiple organ failure: pathophysiology and potential future therapy.
        Ann Surg. 1992; 216: 117
        • Pastores S.M.
        • Katz D.P.
        • Kvetan V.
        Splanchnic ischemia and gut mucosal injury in sepsis and the multiple organ dysfunction syndrome.
        Am J Gastroenterol. 1996; 91: 16
        • Marshall J.C.
        • Christo N.V.
        • Meakins J.L.
        The gastrointestinal tract. The ‘undrained abscess’ of multiple-organ failure.
        Ann Surg. 1993; 218: 111
        • Anup R.
        • Aparna V.
        • Pulimood A.
        • Balasubramanian K.A.
        Surgical stress and the small intestine: role of oxygen free radicals.
        Surgery. 1999; 125: 560-569
        • Thomas Simmy
        • Anup R.
        • Susama P.
        • Vidyasagar S.
        • Balasubramanian K.A.
        Nitric oxide protects the intestine from the damage induced by laparotomy and gut manipulation.
        J Surg Res. 2001; 99: 25-32
        • Prabhu R.
        • Anup R.
        • Balasubramanian K.A.
        Surgical stress induces phospholipid degradation in the intestinal brush border membrane.
        J Surg Res. 2000; 94: 178-184
        • Anup R.
        • Susama P.
        • Balasubramanian K.A.
        Intestinal mitochondrial dysfunction induced by surgical stress.
        J Surg Res. 2001; 99: 120-128
        • Rossmann J.E.
        • Caty M.G.
        • Zheng S.
        • Karamanoukian H.L.
        • Thusu K.
        • Azizkhan R.G.
        • et al.
        Mucosal protection from intestinal ischemia-reperfusion reduces oxidant injury to the lung.
        J Surg Res. 1997; 73: 41-46
        • Blomvist B.I.
        • Hammarqvist F.
        • Von der Decken A.
        • Wernerman J.
        Glutamine and a-ketoglutarate attenuate the fall in muscle free glutamine concentration after total hip replacement.
        Clin Nutr. 1993; 12: 12S-13S
        • Parry-Billings M.
        • Baigrie R.J.
        • Lamont P.M.
        • Morris P.J.
        • Newsholme E.A.
        Effects of major and minor surgery on plasma glutamine and cytokine levels.
        Arch Surg. 1992; 127: 1237-1240
        • Planas M.
        • Schwartz S.
        • Arbos M.A.
        • Farriol M.
        Plasma glutamine levels in septic patients.
        JPEN J Parenter Enteral Nutr. 1993; 17: 299-300
        • Wernerman J.
        • Hammarqvist F.
        • Ali M.R.
        • Vinnars E.
        Glutamine and ornithine-a-ketoglutarate but not branched chain aminoacids reduce the loss of muscle glutamine after surgical trauma.
        Metabolism. 1989; 38: 63-66
        • Parry-Billings M.
        • Evans J.
        • Calder P.C.
        • Newsholme E.A.
        Does glutamine contribute to immunosuppression after major burns?.
        Lancet. 1990; 336: 523-525
        • Griffiths R.D.
        • Jones C.
        • Palmer T.E.
        Six month outcome of critically ill patients given glutamine-supplemented parenteral nutrition.
        Nutrition. 1997; 13: 295-302
        • Zeigler T.R.
        • Young L.S.
        • Benfell K.
        • et al.
        Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation.
        Ann Intern Med. 1992; 116: 821-828
        • Masola B.
        • Evered D.F.
        Preparation of rat enterocyte mitochondria.
        Biochem J. 1984; 218: 441
        • Thomas S.
        • Anup R.
        • Prabhu R.
        • Balasubramanian K.A.
        Effect of surgical manipulation of the rat intestine on enterocyte populations.
        Surgery. 2001; 130: 479-488
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • Randall R.J.
        Protein measurement with the folin phenol reagent.
        J Biol Chem. 1951; 193: 265-275
        • Madesh M.
        • Lakshmi B.
        • Balasubramanian K.A.
        Enterocyte viability and mitochondrial dysfunction after graded intestinal ischemia and reperfusion.
        Mol Cell Biochem. 1997; 167: 81
        • Thomas S.
        • Prabhu R.
        • Pulimood A.
        • Balasubramanian K.A.
        Heat preconditioning prevents enterocyte mitochondrial damage induced by surgical manipulation.
        J Surg Res. 2002; 108: 138-147
        • Parks D.A.
        • William T.K.
        • Beckmann J.S.
        Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine:A reevaluation.
        Am J Physiol. 1988; 254: G768
        • Ohkuma N.
        • Matsuo S.
        • Tsutsui M.
        • Ohkawara A.
        Superoxide dismutase in the epidermis (authors transl).
        Nippon Hifuka Gakkai Zasshi. 1982; 92: 583-590
        • Aebi H.
        Catalase invitro.
        Methods Enzymol. 1984; 105: 121-126
        • Nakamura W.
        • Hosada S.
        • Hayashi K.
        Purification and properties of rat liver glutathione peroxidase.
        Biochem Biophys Acta. 1974; 358: 251-261
        • Awasthi Y.C.
        • Dao D.D.
        • Saneto R.P.
        Interrelationship between anionic and cationic forms of glutathione-S-transferases of human liver.
        Biochem J. 1980; 191: 1-10
        • Krawisz J.E.
        • Sharon P.
        • Stenson W.F.
        Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity.
        Gastroenterology. 1984; 87: 1344-1350
        • Ohkawn H.
        • Ohishi N.
        • Yagi K.
        Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.
        Anal Biochem. 1979; 95: 351-358
        • Bligh E.G.
        • Dyer W.J.
        A rapid method of total lipid extraction and purification.
        Can J Biochem Physiol. 1959; 37: 911-915
        • Chan H.W.S.
        • Levett G.
        Autoxidation of methyl linoeate. Separation and analysis of isomeric mixtures of methyl linoeate hydroperoxides and methyl hydroxylinoeates.
        Lipids. 1977; 12: 99-104
        • Faris M.W.
        • Reed D.J.
        HPLC of thiols and disulphides, dinitrophenol derivatives.
        Methods Enzymol. 1987; 143: 101
        • Thomas S.
        • Karnik S.
        • Balasubramanian K.A.
        Surgical manipulation of the small intestine and its effect on the lung.
        J Surg Res. 2002; 106: 145-156
        • Johnson K.J.
        • Fantone J.C.
        • Kaplan J.
        • Ward P.A.
        In vivo damage of rat lungs by oxygen metabolites.
        J Clin Invest. 1981; 67: 983-993
        • Souba W.W.
        • Smith R.J.
        • Wilmore D.W.
        Glutamine metabolism by the intestinal tract.
        J Parenter Enteral Nutr. 1985; 9: 608-617
        • AQSouba W.W.
        • Klimberg V.S.
        • Plumley D.A.
        • et al.
        The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection.
        J Surg Res. 1990; 48: 383-391
        • Rombeau J.L.
        A review of the effects of glutamine-enriched diets on experimentally induced enterocolitis.
        JPEN J Parenter Enteral Nutr. 1990; 14: 100S-105S
        • O'Dwyer S.T.
        • Smith R.J.
        • Hwang T.L.
        • Wilmore D.W.
        Maintenance of small bowel mucosa with glutamine-enriched parenteral nutrition.
        JPEN J Parenter Enteral Nutr. 1989; 13: 579-585
        • Anup R.
        • Susama P.
        • Balasubramanian K.A.
        The role of xanthine oxidase in small bowel mucosal dysfunction after surgical stress.
        Br J Surg. 2000; 87: 1094-1101
        • Babu R.
        • Eaton S.
        • Drake D.P.
        • Spitz L.
        • Pierro A.
        Glutamine and glutathione counteract the inhibitory effects of mediators of sepsis in neonatal hepatocytes.
        J Pediatr Surg. 2001; 36: 282-286
        • Hong R.W.
        • Round J.D.
        • Helton W.S.
        • Robinson M.K.
        • Wilmore D.W.
        Glutamine preserves liver glutathione after lethal hepatic injury.
        Ann Surg. 1992; 215: 114-119
        • Pinkus L.M.
        • Windmueller H.G.
        Phosphate-dependent glutaminase of small intestine and localisation and role in intestinal glutamine metabolism.
        Arch Biophys Biochem. 1990; 182: 506
        • Clark E.C.
        • Patel S.D.
        • Chadwick P.R.
        • Warhurst G.
        • Carlson G.L.
        Glutamine deprivation facilitates tumor necrosis factor induced bacterial translocation in caco-2 cells by depletion of enterocyte fuel substrate.
        Gut. 2003; 52: 224
        • Cao Y.
        • Feng Z.
        • Hoos A.
        • Kilmberg V.S.
        Glutamine enhances gut glutathione production.
        JPEN J Parenter Enteral Nutr. 1998; 22: 224
        • Dumaswala U.J.
        • Zhuo L.
        • Mahajan S.
        • Nair P.N.
        • Shertzer H.G.
        • Dibello P.
        • et al.
        Glutathione protects chemokine-scavenging and antioxidative defense functions in human RBCs.
        Am J Physiol. 2001; 280: C867-C873
        • Aukrust P.
        • Svardal A.M.
        • Muller F.
        • Lunden B.
        • Berge R.K.
        • Ueland P.M.
        • et al.
        Increased levels of oxidised glutathione in CD4+ lymphocytes associated with disturbed intracellular redox balance in human immunodeficiency virus type 1 infection.
        Blood. 1995; 86: 258-267
        • Hong R.W.
        • Helton W.S.
        • Rounds J.D.
        • Wilmore D.W.
        Glutamine supplemented TPN preserves hepatic glutathione and improves survival following chemotherapy.
        Surg Forum. 1990; 41: 9
        • Espat N.J.
        • Watkins K.T.
        • Lind D.S.
        • Weis J.K.
        • Copeland E.M.
        • Souba W.W.
        Dietary modulation of aminoacid transport in rat and human liver.
        J Surg Res. 1996; 63: 263-268
        • Hammarqvist F.
        • Luo J.L.
        • Cotgreave I.A.
        • Andersson K.
        • Wernerman J.
        Skeletal muscle glutathione is depleted in critically ill patients.
        Crit Care Med. 1997; 25: 78-84
        • Harward T.R.
        • Coe D.
        • Souba W.W.
        • Klingman N.
        • Seeger J.M.
        Glutamine preserves gut glutathione levels during intestinal ischemia/reperfusion.
        J Surg Res. 1994; 56: 351-355
        • Prem J.T.
        • Eppinger M.
        • Lemmon G.
        • Miller S.
        • Nolan D.
        • Peoples J.
        The role of glutamine in skeletal muscle ischemia/reperfusion injury in the rat hind limb model.
        Am J Surg. 1999; 178: 147-150
        • Martensson J.
        • Jain A.
        • Meister A.
        Glutathione is required for intestinal function.
        Proc Natl Acad Sci U S A. 1990; 87: 1715-1719
        • Klimberg V.S.
        • Salloum R.M.
        • Kasper M.
        • Plumley D.A.
        • Dolson D.J.
        • Hautamaki R.D.
        • et al.
        Oral glutamine accelerates healing of the small intestine and improves outcome after whole abdominal radiation.
        Arch Surg. 1990; 125: 1040-1045
        • Marks S.L.
        • Cook A.K.
        • Reader R.
        • Kass P.H.
        • Theon A.P.
        • Greve C.
        • et al.
        Effects of glutamine supplementation of an aminoacid-based purified diet on mucosal integrity in cats with methotrexate-induced enteritis.
        Am J Vet Res. 1999; 60: 755-763