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Open AccessArticle

Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

1
Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands
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Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6200, The Netherlands
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Department of Molecular Biomedical Research, VIB, Ghent B-9000, Belgium
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Department of Biomedical Molecular Biology, Ghent University, Ghent B-9000, Belgium
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Department of Anatomy & Embryology, Maastricht University Medical Center, Maastricht 6200, The Netherlands
*
Author to whom correspondence should be addressed.
Nutrients 2015, 7(7), 5217-5238; https://doi.org/10.3390/nu7075217
Received: 12 May 2015 / Revised: 15 May 2015 / Accepted: 18 June 2015 / Published: 29 June 2015
Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues. View Full-Text
Keywords: arginase; arginine; citrulline; microcirculation; nitric oxide arginase; arginine; citrulline; microcirculation; nitric oxide
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Wijnands, K.A.; Meesters, D.M.; Van Barneveld, K.W.; Visschers, R.G.; Briedé, J.J.; Vandendriessche, B.; Van Eijk, H.M.; Bessems, B.A.; Hoven, N.V.; Von Wintersdorff, C.J.; Brouckaert, P.; Bouvy, N.D.; Lamers, W.H.; Cauwels, A.; Poeze, M. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity. Nutrients 2015, 7, 5217-5238.

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