N. Neveux

Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection

Objective: Arginine supplementation seems logical in situations where this amino acid becomes essential, for example after massive intestinal resection. Arginine is taken up and metabolised by the liver to a large extent and its supplementation is potentially unsafe. Citrulline is not captured by the liver and passes freely to the kidneys where it is metabolised to arginine, and so is a good candidate to generate arginine and thereby improve nutritional status. Methods: Twenty four rats were assigned to four groups: citrulline, arginine, control, and sham. The sham group underwent transection and the three other groups resection of 80% of the small intestine. All rats were fed by enteral nutrition and its composition was as follows: supplementation with citrulline in the citrulline group, supplementation with arginine in the arginine group, and standard polymeric enteral nutrition in the control and sham groups. All groups received isonitrogenous nutrition and citrulline and arginine intakes were equimolar in their respective groups. After 10 days, the rats were sacrificed. Results: Arginine concentration was higher (p<0.05) in plasma and muscle in the citrulline group than in the three other groups. Plasma levels of arginine were 110 (12), 79 (7), 167 (22), and 228 (13) μmol/l in the sham, control, arginine, and citrulline groups respectively. Arginine concentrations in the gastrocnemius were: 0.15 (0.02), 0.16 (0.02), 0.40 (0.05), and 0.94 (0.20) μmol/g, respectively. Citrulline preserved nitrogen balance in resected rats but not in arginine supplemented rats (mean J10: 2.27 (0.29), 1.67 (0.15), 1.98 (0.29), and 2.43 (0.41) g/24 hours in the sham, control, arginine, and citrulline groups, respectively). Conclusion: Supplementing the diet with citrulline is a very efficient means of increasing arginine levels and improving nitrogen balance after massive intestinal resection. The results of this study form a strong rationale for citrulline supplementation in these patients.

Hepatic preservation, liposomally entrapped adenosine triphosphate and nitric oxide production: a study of energy state and protein metabolism in the cold-stored rat liver.

Background: Liposomally entrapped adenosine triphosphate (ATP) has been demonstrated to improve energy state and function of the cold-stored liver. The increased nitrite release associated with liposome administration led us to investigate the interactions between liposome supply and nitric oxide (NO) production through the use of L-NAME, a non-selective inhibitor of NO synthesis. Methods: Twenty-four livers from fasted rats were stored for 18 h at +4°C in University of Wisconsin solution directly (control group) or after infusion with ATP-containing liposomes (Lip-ATP), L-NAME (L-NAME) or both (Lip-ATP-L-NAME). Metabolic fluxes, cell volume and energy state were studied during reperfusion. Results: After storage, nitrite release was increased by 61% in the Lip-ATP group, markedly decreased in the Lip-ATP-L-NAME group and almost abolished in the L-NAME group. The ATP content was increased by 20% in the Lip-ATP group ( P < 0.05 versus control) and on reperfusion this was associated with an increase in cell volume (17%; P < 0.05) and a decrease in branched-chain amino acid release (21%; P < 0.01). The simultaneous addition of L-NAME did not affect these results, but induced a large (6-fold) increase in glucose production, possibly related to the metabolism of glycerol supplied by the liposomes. In the L-NAME group, global amino acid release was 50% lower and was associated with a dramatic decrease in urea production while the energy state deteriorated rapidly. Conclusions: The improvement in energy state and anabolic cell swelling induced by ATP-containing liposomes seems to be independent of NO synthesis. On the other hand, inhibition of NO synthesis appears to exert a detrimental effect on the liver, presumably through the decrease in hepatic energy content.

Effect of apoE/ATP-containing liposomes on hepatic energy state

Background/Aims: ATP‐containing liposomes partially prevent ATP depletion in the cold‐stored liver. As hepatocytes can specifically bind apoE, we investigated whether the addition of apoE to large (200 nm) ATP‐containing liposomes increases their uptake by the liver and further improves hepatic energy stores.

Protective effects of regulatory amino acids on ischaemia-reperfusion injury in the isolated perfused rat liver

Objective. Some amino acids (AAs) display potent regulatory activities on cell metabolism, including via anti-oxidative defences. The aim of this study was to evaluate the protective effect of these AAs on warm ischaemia-reperfusion (I/R) injury in the isolated perfused rat liver. Material and methods. Livers from fasted male Sprague-Dawley rats were isolated and perfused without (control group) or with (AP group) a mixture of regulatory AAs (glutamine, histidine, leucine, methionine, proline, phenylalanine, tryptophan and alanine). After 45 min of perfusion, warm ischaemia was induced for 45 min by clamping the portal vein catheter; thereafter, reperfusion was performed for 30 min. Results. TNF-α production was significantly lower in the AP group during reperfusion (Control: 39±7 versus AP: 16±2 pg min−1 g−1, p<0.05), and lactate dehydrogenase (LDH) release decreased significantly during the last 15 min of reperfusion (Control: 0.13±0.03 versus AP: 0.04±0.02 IU min−1 g−1, p<0.05), despite similar levels of oxidative stress. The addition of regulatory AAs was not associated with variations in portal flow, bile flow, hepatic glucose or urea metabolism. However, significant changes in intrahepatic glutamine (Control: 1.4±0.2 versus AP: 2.6±0.5 µmol g−1, p<0.05) together with higher glutamate release in the AP group (Control: 10.2±5.4 versus AP: 42.6±10.9 nmol min−1 g−1, p<0.05) indicated modifications in nitrogen metabolism. Conclusions. Taken together, the lower TNF-α production, suggesting decreased inflammatory response, the decrease in LDH release in the AP group, demonstrating a better preservation of liver viability, and the increase in hepatic glutamine indicate that AAs play an important role in the livers response to I/R.

PP054-SUN: Immunonutrition: Effect of age on Arginine and Related Amino Acids Systemic Bioavailability After Surgical Stress

gastrointestinal disorders. However, inappropriate chronic exposure and/or prescription have been recently associated with a number of adverse events, especially in the elderly. Among known drug-class effects of PPI, hypomagnesaemia has been recently shown by a growing number of case reports and series. However, epidemiological studies addressing this topic, especially in older subjects, are still needed. Methods: We cross-sectionally investigated the relationship between PPI use and magnesium status in a large cohort of community-dwelling older volunteers from the Baltimore Longitudinal Study of Aging (BLSA). 4017 older subjects 65 years or older (1983 women and 2034 men) with complete data on serum magnesium levels and PPI use were evaluated. Subjects were categorized according to PPI use. Linear regression models adjusted for age and sex (Model 1) and for additional confounders including BMI, mineral and magnesium supplements, creatinine, calcium serum levels, TSH, use of diuretics, digitalis, antibiotics, calcineurin inhibitors, presence of chronic disease (type 2 diabetes, cardiovascular diseases, cancer) (Model 2) were used to address the relationship between PPI use and serum magnesium levels. Results: 505 subjects (12.6%) were PPI users. After adjustment for age and sex, PPI users exhibited significantly lower magnesium levels than non-users counterpart (1.99±0.22 vs 2.03±0.20mg/ml, p < 0.001). PPI use was negatively associated with serum magnesium levels independent of multiple confounders ( 0.041±0.009, p < 0.0001). Conclusion: In community-dwelling older subjects the use of PPIs is negatively and independently associated with serum magnesium levels.