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

Nutrients

Karolina A.P. Wijnands⁴  Dennis M. Meesters⁴  Kevin W.Y. van Barneveld⁴  Ruben G.J. Visschers⁴  Jacob J. Briedé¹  Benjamin Vandendriessche³  Hans M.H. van Eijk⁴  Babs A.F.M. Bessems⁴  Nadine van den Hoven⁴  Christian J.H. von Wintersdorff⁴  Peter Brouckaert³  Nicole D. Bouvy⁴  Wouter H. Lamers²  Anje Cauwels³ 

[1] Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6200, The Netherlands; E-Mail:;Department of Anatomy & Embryology, Maastricht University Medical Center, Maastricht 6200, The Netherlands; E-Mail:;Department of Molecular Biomedical Research, VIB, Ghent B-9000, Belgium; E-Mails:;Department of Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, The Netherlands; E-Mails:

关键词: arginase;    arginine;    citrulline;    microcirculation;    nitric oxide;   

DOI  :  10.3390/nu7075217

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
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