Endotoxemia affects citrulline, arginine and glutamine bioavailability
Nathalie Neveux
Laboratoire de Biologie de la Nutrition, UPRES EA 4466, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes
Service de Biochimie interhospitalier, Hôtel Dieu-Cochin, AP-HP, Paris, France
Search for more papers by this authorLuc Cynober
Laboratoire de Biologie de la Nutrition, UPRES EA 4466, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes
Service de Biochimie interhospitalier, Hôtel Dieu-Cochin, AP-HP, Paris, France
Search for more papers by this authorChristophe Moinard
Laboratoire de Biologie de la Nutrition, UPRES EA 4466, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes
Search for more papers by this authorNathalie Neveux
Laboratoire de Biologie de la Nutrition, UPRES EA 4466, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes
Service de Biochimie interhospitalier, Hôtel Dieu-Cochin, AP-HP, Paris, France
Search for more papers by this authorLuc Cynober
Laboratoire de Biologie de la Nutrition, UPRES EA 4466, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes
Service de Biochimie interhospitalier, Hôtel Dieu-Cochin, AP-HP, Paris, France
Search for more papers by this authorChristophe Moinard
Laboratoire de Biologie de la Nutrition, UPRES EA 4466, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes
Search for more papers by this authorAbstract
Eur J Clin Invest 2012; 42 (3): 282–289
Background Sepsis considerably alters the intestinal barrier functions, which in turn modify the absorption and bioavailability of nutrients. However, the effects of septic shock on aminoacid (AAs) bioavailability are poorly documented. The aim of this study was to compare the bioavailability of citrulline, arginine and glutamine during endotoxemia.
Materials and methods Thirty-six rats were randomised into two groups: control and lipopolysaccharides (LPS). The LPS group received an intraperitoneal injection of endotoxins (7·5 mg/kg). After 12 h, each group was again randomised into three subgroups, each of which received an oral bolus of citrulline, arginine or glutamine (5·7 mmol/kg). Blood samples were collected at various times from 0 to 600 min after AA administration. The concentrations of citrulline, arginine, glutamine and their metabolites arginine and ornithine were measured to determine pharmacokinetic parameters Area Under Curve (AUC), Cmax and Tmax.
Results The AUC values of citrulline decreased in LPS rats [citrulline, control: 761 ± 67 and LPS: 508 ± 72 μmol min/mL (P = 0·02)]. Maximum concentrations of citrulline were also significantly decreased by endotoxemia (P = 0·01). The pharmacokinetic parameters of arginine and glutamine were not significantly modified by endotoxemia. The AUC value of arginine from citrulline conversion was diminished in endotoxemic rats. The other pharmacokinetic parameters of arginine were not significantly modified after arginine or citrulline supply in either group (control or LPS).
Conclusion Endotoxemia affects the bioavailability of AAs differently according to the amino acid considered. This feature may be important for nutritional strategy in ICU patients.
References
- 1 Annane D, Aegerter P, Jars-Guincestre MC, Guidet B. Current epidemiology of septic shock: the CUB-Rea Network. Am J Respir Crit Care Med 2003; 168: 165–72.
- 2 Blackwell TS, Christman JW. Sepsis and cytokines: current status. Br J Anaesth 1996; 77: 110–7.
- 3 Vente JP, von Meyenfeldt MF, van Eijk HM, van Berlo CL, Gouma DJ, van der Linden CJ et al. Plasma-amino acid profiles in sepsis and stress. Ann Surg 1989; 209: 57–62.
- 4 Luiking YC, Poeze M, Dejong CH, Ramsay G, Deutz NE. Sepsis: an arginine deficiency state? Crit Care Med 2004; 32: 2135–45.
- 5 Suchner U, Kuhn KS, Furst P. The scientific basis of immunonutrition. Proc Nutr Soc 2000; 59: 553–63.
- 6 Popovic PJ, Zeh HJ 3rd, Ochoa JB. Arginine and immunity. J Nutr 2007; 137: 1681S–6S.
- 7 Osowska S, Moinard C, Neveux N, Loi C, Cynober L. Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection. Gut 2004; 53: 1781–6.
- 8 Ligthart-Melis GC, van de Poll MC, Boelens PG, Dejong CH, Deutz NE, van Leeuwen PA. Glutamine is an important precursor for de novo synthesis of arginine in humans. Am J Clin Nutr 2008; 87: 1282–7.
- 9 Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Benazeth S et al. Almost all about citrulline in mammals. Amino Acids 2005; 29: 177–205.
- 10 Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 2008; 65: 51–9.
- 11 Wijnands K.A., Vink H., Buurman W.A., Lamers W.H., Poeze M. Citrulline supplementation improves the microcirculation through the arginine-NO metabolism in sepsis. Int Care Med 2010; 35: S89.
- 12 Husson A, Brasse Lagnel C., Fairand A., Renouf S., Lavoinne A. Argininosuccinate synthetase from the urea cycle to the citrulline-NO cycle. Eur J Biochem 2003; 270: 1887–99.
- 13 Xu DZ, Lu Q, Deitch EA. Nitric oxide directly impairs intestinal barrier function. Shock 2002; 17: 139–45.
- 14 Gardiner KR, Ahrendt GM, Gardiner RE, Barbul A. Failure of intestinal amino acid absorptive mechanisms in sepsis. J Am Coll Surg 1995; 181: 431–6.
- 15 Sodeyama M, Gardiner KR, Regan MC, Kirk SJ, Efron G, Barbul A. Sepsis impairs gut amino acid absorption. Am J Surg 1993; 165: 150–4.
- 16 Bistrian BR. Practical recommendations for immune-enhancing diets. J Nutr 2004; 134: 2868S–72S.
- 17 Cynober L. We must improve our understanding of the basic mechanisms of the different phases of sepsis. Clin Nutr 2008; 27: 311–2.
- 18 Fink MP, Heard SO. Laboratory models of sepsis and septic shock. J Surg Res 1990; 49: 186–96.
- 19 Neveux N, David P, Cynober L. Measurement of amino acid concentration in biological fluids and tissues using ion-exchange chromatography. In: LA Cynober, editor. Metabolic and Therapeutic Aspects of Amino Acids in Clinical Nutrition, 2nd edn. Boca Raton, FL: CRC Press, 2004: pp 17–28.
- 20 Team RDC. A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2008.
- 21 Novak F, Heyland DK, Avenell A, Drover JW, Su X. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 2002; 30: 2022–9.
- 22 Wernerman J, Hammarqvist F. Glutamine: a necessary nutrient for the intensive care patient. Int J Colorectal Dis 1999; 14: 137–42.
- 23 Galban C, Montejo JC, Mesejo A, Marco P, Celaya S, Sanchez-Segura JM et al. An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients. Crit Care Med 2000; 28: 643–8.
- 24 Bruins MJ, Soeters PB, Lamers WH, Deutz NE. L-arginine supplementation in pigs decreases liver protein turnover and increases hindquarter protein turnover both during and after endotoxemia. Am J Clin Nutr 2002; 75: 1031–44.
- 25 Loi C, Zazzo JF, Delpierre E, Niddam C, Neveux N, Curis E et al. Increasing plasma glutamine in postoperative patients fed an arginine-rich immune-enhancing diet – a pharmacokinetic randomized controlled study. Crit Care Med 2009; 37: 501–9.
- 26 Wang Q, Wang JJ, Boyce S, Fischer JE, Hasselgren PO. Endotoxemia and IL-1 beta stimulate mucosal IL-6 production in different parts of the gastrointestinal tract. J Surg Res 1998; 76: 27–31.
- 27 Gardiner KR, Gardiner RE, Barbul A. Reduced intestinal absorption of arginine during sepsis. Crit Care Med 1995; 23: 1227–32.
- 28 Abad B, Mesonero JE, Salvador MT, Garcia-Herrera J, Rodriguez-Yoldi MJ. Tumor necrosis factor-alpha mediates inhibitory effect of lipopolysaccharide on L-leucine intestinal uptake. Dig Dis Sci 2002; 47: 1316–22.
- 29 Salloum RM, Copeland EM, Souba WW. Brush border transport of glutamine and other substrates during sepsis and endotoxemia. Ann Surg 1991; 213: 401–9.
- 30 Bahri S, Curis E, El Wafi FZ, Aussel C, Chaumeil JC, Cynober L et al. Mechanisms and kinetics of citrulline uptake in a model of human intestinal epithelial cells. Clin Nutr 2008; 27: 872–80.
- 31 Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y. CATs and HATs: the SLC7 family of amino acid transporters. Pflugers Arch 2004; 447: 532–42.
- 32 Closs EI, Simon A, Vekony N, Rotmann A. Plasma membrane transporters for arginine. J Nutr 2004; 134: 2752S–9S.
- 33 Bode BP. Recent molecular advances in mammalian glutamine transport. J Nutr 2001; 131: 2475S–85S.
- 34 Piton G, Manzon C, Monnet E, Cypriani B, Barbot O, Navellou JC et al. Plasma citrulline kinetics and prognostic value in critically ill patients. Intensive Care Med 2010; 36: 702–6.
- 35 Hattori Y, Shimoda S, Gross SS. Effect of lipopolysaccharide treatment in vivo on tissue expression of argininosuccinate synthetase and argininosuccinate lyase mRNAs: relationship to nitric oxide synthase. Biochem Biophys Res Commun 1995; 215: 148–53.
- 36 Nagasaki A, Gotoh T, Takeya M, Yu Y, Takiguchi M, Matsuzaki H et al. Coinduction of nitric oxide synthase, argininosuccinate synthetase, and argininosuccinate lyase in lipopolysaccharide-treated rats. RNA blot, immunoblot, and immunohistochemical analyses. J Biol Chem 1996; 271: 2658–62.
- 37 Yu YM, Ryan CM, Burke JF, Tompkins RG, Young VR. Relations among arginine, citrulline, ornithine, and leucine kinetics in adult burn patients. Am J Clin Nutr 1995; 62: 960–8.
- 38 Yu YM, Ryan CM, Castillo L, Lu XM, Beaumier L, Tompkins RG et al. Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal. Am J Physiol Endocrinol Metab 2001; 280: E509–17.
- 39 Hankard RG, Darmaun D, Sager BK, D’Amore D, Parsons WR, Haymond M. Response of glutamine metabolism to exogenous glutamine in humans. Am J Physiol 1995; 269: E663–70.
- 40 Haque SM, Chen K, Usui N, Iiboshi Y, Okuyama H, Masunari A et al. Effects of endotoxin on intestinal hemodynamics, glutamine metabolism, and function. Surg Today 1997; 27: 500–5.
- 41 Souba WW, Herskowitz K, Klimberg VS, Salloum RM, Plumley DA, Flynn TC et al. The effects of sepsis and endotoxemia on gut glutamine metabolism. Ann Surg 1990; 211: 543–9.
- 42 Brand K, Leibold W, Luppa P, Schoerner C, Schulz A. Metabolic alterations associated with proliferation of mitogen-activated lymphocytes and of lymphoblastoid cell lines: evaluation of glucose and glutamine metabolism. Immunobiology 1986; 173: 23–34.
- 43 Ardawi MS, Majzoub MF, Kateilah SM, Newsholme EA. Maximal activity of phosphate-dependent glutaminase and glutamine metabolism in septic rats. J Lab Clin Med 1991; 118: 26–32.
- 44 Austgen TR, Chen MK, Dudrick PS, Copeland EM, Souba WW. Cytokine regulation of intestinal glutamine utilization. Am J Surg 1992; 163: 174–9.
- 45 Nose K, Wasa M, Okada A. Gut glutamine metabolism at different stages of sepsis in rats. Surg Today 2002; 32: 695–700.
- 46 Neilly PJ, Gardiner KR, Kirk SJ, O’Hare M, Jennings G, Anderson NH et al. Topical glutamine therapy in experimental inflammatory bowel disease. Clin Nutr 1995; 14: 283–7.
- 47 Moinard C, Cynober L. Citrulline: a new player in the control of nitrogen homeostasis. J Nutr 2007; 137: 1621S–5S.
- 48 Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L et al. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab 2006; 291: E582–6.
