The kidney is not the only organ affected by the accumulation of dCML. Its high accumulation in other tissues and organs may also, however, have important physiological consequences.

Milk proteins are frequently used as supplements in fortified foods. However, processing produces chemical changes which likely affect the nutritional advantage. This study was intended to explore the possible difference in digestibility between extruded and non-extruded caseins and how the dietary N (ε) -carboxymethyllysine (CML) is metabolised. Normal rats were randomized into either an extruded protein diet (EP) or the same with unextruded proteins (UEP), for two periods of 2 weeks at 7 to 9 and 11 to 13 weeks of age. However, no difference in protein digestibility was detected between the two diets, either in young or in adult animals, despite a 9.4-fold higher level of CML and an 8.5-fold higher level of lysinoalanine in the EP than in the UEP. No diet-related changes were observed in plasma CML, either protein bound or free. Amounts of 38 and 48 % of the orally absorbed CML were excreted in urine and faeces, respectively, in UEP-fed rats. Lower rates of excretion were found in the EP-fed rats (23 and 37 %, respectively). A second animal study using a single oral dose of free CML (400 μg/rat) was set up to measure the systemic concentration of CML every hour from 0 to 4 h. It revealed that protein-bound CML was not affected by the oral dose of CML, and the highest free CML level found in the circulation was 600 ng/mL. Extruded proteins, therefore, appear to be well digested, and CML rapidly eliminated. Since its elimination is, however, incomplete, the question of its biodistribution and metabolism remains open.

Chronic CML ingestion induced endothelial dysfunction, arterial stiffness and aging in a RAGE-dependent manner.

Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms.

This article is protected by copyright. All rights reserved. AbstractScope: Formula-derived Dietary Advanced Glycation End products (AGEs) may promote programming of inflammation and oxidative stress in the kidney of intrauterine growth retarded (IUGR) piglets. Methods and results:IUGR piglets received either a Low Temperature Heated Formula (LHF: n=8) or a High Temperature Heated Formula (HHF: n=8) or suckled naturally for 3 weeks postnatally. Then they were fed with normal ad libutum regular diet. Nɛ carboxymethyllysine (CML) was measured in plasma, feces and formula by HPLC/MS-MS.CML was detected by immunofluoresence in kidney cells. Target renin-angiotensin, apoptotic, proinflammatory genes, p62 NF-κB and sRAGE levels were quantified. Compared with that in controls, free CML and plasma urea increased significantly in the HHF fed group at PND36 (P<0.05). CML was detected in nuclei of renal tubular cells of fed formula piglets but not in suckled ones. This presence of CML was associated with the activation of the soluble sRAGE. AT1, AT2, caspase 3, caspase 8, NF-κB, p62 NF-κB and total protein oxidation in kidney were higher in HHF fed group as compared to LHF fed group (P<0.05). Conclusion:Food processes aimed at reducing the concentration of AGEs in infant formula are urgently needed and may be therapeutically relevant for premature and/or IUGR babies.