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High doses of dietary arginine during repletion impair weight gain and increase infectious mortality in protein-malnourished mice

Published online by Cambridge University Press:  09 March 2007

Michael D. Peck ,
George F. Babcock ,
J. Wesley Alexander ,
Timothy Billiar  and
Juan Ochoa
Michael D. Peck
Affiliation:
Department of Surgery, University of Miami School of Medicine, Miami, Florida 33101, USA
George F. Babcock
Affiliation:
Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio 45229, USA
J. Wesley Alexander
Affiliation:
Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio 45229, USA
Timothy Billiar
Affiliation:
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA
Juan Ochoa
Affiliation:
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA
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Abstract

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There is considerable evidence for the beneficial effects of dietary arginine, a conditionally essential amino acid that enhances anabolism and T-cell function. However, the safety and efficacy of higher doses of arginine supplementation following infection have not been investigated completely. These issues were explored therefore, in a murine model of malnutrition and infection. Severe protein malnutrition was induced by feeding mice for 6 weeks on an isoenergetic diet containing only 10 g protein/kg. Mice were then allowed to consume diets with normal amounts of protein (200 g/kg) with 50 g/kg provided as amino acid mixtures of glycine and arginine in which the arginine content ranged from 0 to 50 g/kg. During the repletion period a significant weight gain was noted in the groups fed on diets with either 10 or 20 g arginine/kg, but not in the group fed on the diet with 50 g arginine/kg, compared with the diet with 0 g arginine/kg. Mortality rates after infection with Salmonella typhimurium were not decreased by the addition of 10 or 20 g arginine/kg to the diet, and were in fact worsened by supplementation with 50 g arginine/kg. The results of the present study showed that not only are the beneficial effects of arginine supplementation after infection lost when high doses are administered, but also that these high doses become toxic. Mice fed on higher doses showed significant impairment of weight gain and an increase in mortality rates.

Keywords

ArginineMalnutritionInfection
Type
Arginine supplementation and malnutrition
Information
British Journal of Nutrition , Volume 74 , Issue 6 , December 1995 , pp. 787 - 795
Copyright
Copyright © The Nutrition Society 1995

References

American Institute of Nutrition (1977). Report of the American Institute of Nutrition Ad HOC Committee on Standards for Nutritional Studies. Journal of Nutrition 107, 1340–1348.Google Scholar
Barbul, A., Fishel, R. S., Shimazu, S., Wasserkrug, H. L., Yoshimura, N. N., Tao, R. C. & Efron, G. (1985). Intravenous hyperalimentation with high arginine levels improves wound healing and immune function. Journal of Surgical Research 38, 328–334.CrossRefGoogle ScholarPubMed
Barbul, A., Sisto, D. A., Waserkrug, H. L. & Efron, G. (1981). Arginine stimulates lymphocyte immune response in healthy human beings. Surgery 90, 244–251.Google ScholarPubMed
Barbul, A., Wasserkrug, H. L., Seifter, E., Rettura, G., Levenson, S. M. & Efron, G. (1980 a). Immunostimulatory effects of arginine in normal and injured rats. Journal of Surgical Research 29, 228–235.CrossRefGoogle ScholarPubMed
Barbul, A., Wasserkrug, H. L., Sisto, D. A., Seifter, E., Rettura, G., Levenson, S. M. & Efron, G. (1980 b). Thymic stimulatory actions of arginine. Journal of Parenteral and Enteral Nutrition 4, 446–449.CrossRefGoogle ScholarPubMed
Barbul, A., Wasserkrug, H. L., Yoshimura, N. N., Tao, R. & Efron, G. (1984). High arginine levels in intravenous hyperalimentation abrogate post-traumatic immune suppression. Journal of Surgical Research 36, 620–624.CrossRefGoogle ScholarPubMed
Billiar, T. R., Curran, R. D., Stuehr, D. J., West, M. A., Bentz, B. G. & Simmons, R. L. (1989). An L-arginine-dependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro. Journal of Experimental Medicine 169, 1467–1472.CrossRefGoogle ScholarPubMed
Biozzi, G., Mouton, D., Sant'Anna, O. A., Passos, H. C., Gennari, M., Reis, M. H., Ferreira, V. C., Heumann, A. M., Bouthillier, Y., Ibanez, O. M., Stiffel, C. & Siqueira, M. (1979). Genetics of immunoresponsiveness to natural antigens in the mouse. Current Topics in Microbiology and Immunology 85, 31–98.Google ScholarPubMed
Borman, A., Wood, T. R., Black, H. C., Anderson, E. G., Oesterling, M. J., Womack, M. & Rose, W. C. (1946). The role of arginine in growth with some observations on the effects of arginic acid. Journal of Biological Chemistry 166, 585.CrossRefGoogle Scholar
Daly, J. M., Reynolds, J., Thom, A., Kinsley, L., Dietrick-Gallagher, M., Shou, J. & Ruggieri, B. (1988). Immune and metabolic effects of arginine in the surgical patient. Annals of Surgery 208, 512–516.CrossRefGoogle ScholarPubMed
Gianotti, L., Alexander, J. W., Pyles, T. & Fukushima, R. (1993). Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance: The role of nitric oxide. Annals of Surgery 217, 644–654.CrossRefGoogle ScholarPubMed
Gonce, S. J., Peck, M. D., Alexander, J. W. & Miskell, P. W. (1990). The effect of supplemental arginine on recovery from peritonitis in guinea pigs. Journal of Parenteral and Enteral Nutrition 14, 237–244.CrossRefGoogle Scholar
Hibbs, J. B., Taintor, R. R., Vavrin, Z. & Rachlin, E. M. (1988). Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochemical and Biophysical Research Communications 157, 87–94.CrossRefGoogle ScholarPubMed
Iyamu, J. O. & Adamson, I. (1982). Effect of supplemental arginine on rehabilitation of the starved rat. Nutrition Reports International 26, 335–345.Google Scholar
Kari, F. W., Ulman, E. A., Mulloy, A. L. & Visek, W. J. (1981). Arginine requirement of mature protein-malnourished rats for maximal rate of repletion. Journal of Nutrition 111, 1489–1493.CrossRefGoogle ScholarPubMed
Madden, H. P., Breslin, R. J., Wasserkrug, H. L., Efron, G. & Barbul, A. (1988). Stimulation of T cell immunity by arginine enhances survival in peritonitis. Journal of Surgical Research 44, 658–663.CrossRefGoogle ScholarPubMed
Mulloy, A. L., Kari, F. W. & Visek, W. J. (1982). Dietary arginine, insulin secretion, glucose tolerance and liver lipids during repletion of protein-depleted rats. Hormonal and Metabolic Research 14, 471–475.CrossRefGoogle ScholarPubMed
National Research Council (1985). Guide to the Care and Use of Laboratory Animals. National Institutes of Health Publication no. 86–23. Bethesda, Md: National Institutes of Health.Google Scholar
Ochoa, J. B., Udekwu, A. O., Billiar, T. R., Curran, R. D., Cerra, F. B., Simmons, R. L. & Peitzman, A. B. (1991). Nitrogen oxide levels in patients following trauma and during sepsis. Annals of Surgery 214, 621–626.CrossRefGoogle Scholar
Palmer, R. M. J. (1993). The discovery of nitric oxide in the vessel wall: A unifying concept in the pathogenesis of sepsis. Archives of Surgery 128, 396–401.CrossRefGoogle Scholar
Peck, M. D. & Alexander, J. W. (1992). The interaction of protein and zinc malnutrition with the murine response to infection. Journal of Parenteral and Enteral Nutrition 16. 232–235.CrossRefGoogle ScholarPubMed
Peitzman, A. B. (1991). Nitrogen oxide levels in patients following trauma and during sepsis. Annals of Surgery 214, 621–626.Google Scholar
Saito, H., Trocki, O., Wang, S., Gonce, S. J., Joffe, S. N. & Alexander, J. W. (1987). Metabolic and immune effects of dietary arginine supplementation after burn. Archives of Surgery 122, 784–789.CrossRefGoogle ScholarPubMed
Stucki, W. P. & Harper, A. E. (1962). Effects of altering the ratio of indispensable to dispensable amino acids in diets for rats. Journal of Nutrition 78, 218–286.CrossRefGoogle ScholarPubMed
Stuehr, D. J. & Marletta, M. A. (1985). Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proceedings of National Academy of Sciences USA 82, 7738.CrossRefGoogle ScholarPubMed
Wagner, D. A., Young, V. R. & Tannenbaum, S. R. (1983). Mammalian nitrate biosynthesis: Incorporation of 15NH3 into nitrate is enhanced by endotoxin treatment. Proceedings of National Academy of Sciences USA 80, 4518.CrossRefGoogle ScholarPubMed
Yelich, M. R. & Filkins, J. P. (1983). Insulin hypersecretion and potentiation of endotoxin shock in the rat. Circulatory Shock 9, 589–603.Google Scholar