Endotoxemia affects citrulline, arginine and glutamine bioavailability

Elwafi, F Z; Curis, Emmanuel; Zerrouk, Naïma; Neveux, N.; Chaumeil, Jean‐Claude; Arnaúd, Philippe; Cynober, Luc; Moinard, Christophe

doi:10.1111/j.1365-2362.2011.02581.x

Cited by 29 publications

(21 citation statements)

References 45 publications

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“…In addition, a lower plasma citrulline Critical Care Medicine www.ccmj0urnai.0r9 concentration was associated with a higher CRP concentration and more frequent antibiotic therapy, suggesting that sepsis might be a second factor to explain plasma citrulline reduction (23,24). Indeed, in the present study, plasma citrulline concentration was likely overestimated in case of acute renal failure due to renal accumulation of citrulline.…”

Section: Discussionmentioning

confidence: 54%

Enterocyte Damage in Critically Ill Patients Is Associated With Shock Condition and 28-Day Mortality*

Piton

Belon²,

Cypriani³

et al. 2013

Critical Care Medicine

100

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Section: Discussionmentioning

confidence: 54%

Enterocyte Damage in Critically Ill Patients Is Associated With Shock Condition and 28-Day Mortality*

Piton

Belon²,

Cypriani³

et al. 2013

Critical Care Medicine

100

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“…The effects of L-Citrulline supplementation: enhanced plasma arginine concentration and increased tissue arginine concentration may indicate that insufficient citrulline availability underlies the low arginine levels seen in endotoxemic mice [15], [17], [22]. Such a therapeutic role of L-Citrulline supplementation is also supported by very recent data of Elwafi et al [36], who showed that oral supplementation of L-Citrulline in rats resulted in higher plasma arginine concentrations compared to L-Arginine supplementation during acute endotoxemia [36]. In addition, the therapeutic role of L-Citrulline is not limited to endotoxemic conditions, as L-Citrulline supplementation has been demonstrated to be beneficial in several other pathological conditions associated with limited L-Arginine availability or enhanced arginine catabolism [51]–[54].…”

Section: Discussionmentioning

confidence: 73%

“…The L-Citrulline and L-Arginine dosages were extrapolated from the arginine dosages used in both porcine endotoxemia [34] and a human arginine supplementation study (Luiking, Poeze, Deutz, unpublished data), taking in consideration that the nitrogen requirements in rodents are ten times higher than in humans [35], [36].…”

Section: Methodsmentioning

confidence: 99%

Citrulline a More Suitable Substrate than Arginine to Restore NO Production and the Microcirculation during Endotoxemia

et al. 2012

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BackgroundImpaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia.Methodology/Principal FindingsTo study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg•g bodyweight−1•h−1), combined with either L-Citrulline (6.25 mg•h-1), L-Arginine (6.25 mg•h−1), or L-Alanine (isonitrogenous control; 12.5 mg•h−1) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot.Conclusion/SignificanceL-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the L-Citrulline-supplemented group showed, compared to the endotoxemic and L-Arginine-supplemented endotoxemic group, an increase in degree of phosphorylation of eNOS (Ser 1177) and a decrease in iNOS protein level. In conclusion, L-Citrulline supplementation during endotoxemia and not L-Arginine reduced intestinal microcirculatory dysfunction and increased intracellular NO production, likely via increased intracellular citrulline and arginine availability.

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“…In the FCit group, Cit was given at 1 g Á kg 21 Á d 21 . This dose of Cit was chosen on the basis of our previous studies (20,21). The NEAA supplement contained isomolar amounts of the 6 AAs and was isonitrogenous to Cit.…”

Section: Methodsmentioning

confidence: 99%

Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats

Jegatheesan

Beutheu

Ventura

et al. 2015

The Journal of Nutrition

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Endotoxemia affects citrulline, arginine and glutamine bioavailability

Abstract: Endotoxemia affects the bioavailability of AAs differently according to the amino acid considered. This feature may be important for nutritional strategy in ICU patients.

Cited by 29 publications

References 45 publications

Enterocyte Damage in Critically Ill Patients Is Associated With Shock Condition and 28-Day Mortality*

Enterocyte Damage in Critically Ill Patients Is Associated With Shock Condition and 28-Day Mortality*

Citrulline a More Suitable Substrate than Arginine to Restore NO Production and the Microcirculation during Endotoxemia

Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats

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