Toxicological evaluation of advanced glycation end product Nε-(carboxymethyl)lysine: Acute and subacute oral toxicity studies

Liu, Xin; Zheng, Liangqing; Zhang, Rong; Liu, Gang; Xiao, Shensheng; Qiao, Xiaoting; Wu, Yongning; Gong, Zhiyong

doi:10.1016/j.yrtph.2016.02.013

Cited by 40 publications

(25 citation statements)

References 46 publications

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“…Adverse effects of carboxymethyl lysine (CML) and other AGEs on health are currently a controversial issue, and the relation of dietary AGEs to inflammatory and auto-immune diseases such as diabetic complications and renal failure is under indepth discussion ( Van Nguyen 2006;Poulsen et al 2013;Kizer et al 2014;Bengmark 2007;Liu et al 2016;Nguyen et al 2013;Nass et al 2007). …”

Section: Introductionmentioning

confidence: 99%

The Impact of Different Drying Techniques and Controlled Storage on the Development of Advanced Glycation End Products in Skim Milk Powders Using Isotope Dilution ESI-LC-MS/MS

Aalaei

Sjöholm

Rayner

et al. 2017

Food Bioprocess Technol

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The impact of different drying techniques and storage conditions on the formation of carboxymethyl lysine (CML) as an advanced glycation end product (AGE) was investigated in various pilot-scale produced skim milk powders (SMP). CML, an indicator of advanced stages of the Maillard reaction, was analyzed by isotope dilution ESI-LC-MS/MS after drying and at intervals during storage for 200 days. The aim of this study is to increase the awareness that the development of AGEs can be hindered by controlled storage, which is mostly neglected at the domestic level by the consumers. Pilot-scale freeze-dryer, spray-dryer, and drumdryer were utilized for manufacturing SMPs. The storage was designed in such a way that it simulated how an average consumer keeps the dried products at home, specifically after opening the packages and how the products may be exposed to unfavorable conditions. To do so, four storage conditions including two temperatures (20°C, 30°C) and two relative humidities RH (33%, 52%) were studied and CML formation was monitored using LC-MS/MS. Our results show that the spray-dried samples developed two times higher CML after 200 days, compared to the freeze-dried samples, and this value was 1.6 times for the drum-dried samples. Storage at 52% RH developed 9.8-10 times more CML in the samples, in comparison with 33% RH, at the same storage temperature (P < 0.05). Our findings demonstrate that AGEs, molecules suspected to be involved in risks factors for auto-immune diseases, may be formed during storage of SMPs after opening the packages by the consumers.

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Section: Introductionmentioning

confidence: 99%

The Impact of Different Drying Techniques and Controlled Storage on the Development of Advanced Glycation End Products in Skim Milk Powders Using Isotope Dilution ESI-LC-MS/MS

Aalaei

Sjöholm

Rayner

et al. 2017

Food Bioprocess Technol

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“…Liu et al . () also observed that the free CML level markedly increased MDA levels in the liver and kidneys when a high CML dose was administered to mice, and Elmhiri et al . () reported that the consumption of formula‐derived AGEs (protein‐bound CML) increased MDA levels in the livers of intrauterine growth retardation (IUGR) piglets.…”

Section: Resultsmentioning

confidence: 85%

“…A decrease in the activities of antioxidant enzymes may be due to a decrease in the ability of an organism to remove free radicals. SOD and GSH‐Px activities in the liver and kidneys of mice have been shown to significantly decrease after CML intake (Liu et al ., ). As shown in Fig.…”

Section: Resultsmentioning

confidence: 97%

“…Additionally, overexpression of RAGE perpetuates oxidative stress and contributes to inflammation via nuclear factor‐κB (NF‐κB) upregulation (Tobonvelasco et al ., ), which impairs organ functions (Bengmark, ). Previous studies have focused on oxidative damage in the kidneys (Elmhiri et al ., ), liver (Liu et al ., ) and spleen (Cai et al ., ), mainly due to extensive CML accumulation in these tissues. The most recent research has suggested that the majority of the dietary protein‐bound CML accumulates in the ileum and colon (Tessier et al ., ), but the downstream effects of the AGE‐RAGE interaction in the GI tract are largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

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Accumulation and effects of dietary advanced glycation end products on the gastrointestinal tract in rats

Yuan

Zhao

et al. 2018

Int J of Food Sci Tech

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Summary The gastrointestinal (GI) tract represents the first barrier against the penetration of organisms by dietary advanced glycation end products (AGEs), but the tissue accumulation of AGEs and AGE‐induced effects on the GI tract have yet to be completely elucidated. This study aimed to investigate the tissue accumulation of AGEs and AGE‐induced oxidative stress and inflammation in the GI tract of rats after long‐term consumption of AGEs from bread crust (BC). The GI tract was then removed to analyse carboxymethyllysine (CML) and malondialdehyde (MDA) contents, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) and the levels of tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). This study demonstrates that the oral intake of AGEs promotes their accumulation in the GI tract, and AGEs attenuate the first‐line antioxidant defence and stimulate the inflammatory response of the GI tract by downregulating enzymatic antioxidative pathways and increasing inflammatory cytokine levels.

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“…При изучении подострой токсичности КМЛ, в ре-зультате введения его в дозах 200, 500 и 1000 мг/кг мышам обоего пола в течение 28 дней установлено из-менение биохимических показателей крови и мочи, указывающих на дисфункцию печени и почек у лабо-раторных животных. У испытуемых животных гисто-патологические изменения в основном обнаружены в легких, печени, почках и селезенке [54].…”

Section: российский вестник перинатологии и педиатрии 2018; 63:(4) Runclassified

Maillard Reactions – An Important Factor of the Safety and Quality of Infant Formula

Николаевич¹,

Колин²,

Николаевна³

2018

Ross. vestn. perinatol. pediatr.

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The physicochemical properties of infant adapted milk formulae that affect their tolerability and effectiveness depend on the composition and quality of the raw ingredients, the production process, the storage conditions and the quality control of the finished products. The technology of manufacturing a powdered infant formula includes a variety of methodsfor processing componentsthat make up its composition, including raw milk. This processing is accompanied by a noticeable change in a number of physical, chemical and biological properties of the individual components of milk, their loss, the formation of fundamentally new chemical compounds. The most frequent reactions observed during the heat treatment of milk include the formation of bonds between reactive carbonyl groups of the sugar and the amino groups of amino acids, followed by the appearance of a large number of low- and high-molecular compounds, the so-called Maillard Reaction Products(MRP). The study of MRP in recent years hasincreasingly attracted the attention of medical practitioners because of the discovery of these compounds in infant formula and their potential danger to children’s health. This review provides evidence that powdered infant adapted formulae produced with an original technology based on whole goat milk with a native ratio of the main groups of milk proteins(whey – 20% and casein – 80%) have a minimum potential for unwanted effects associated with MRP.

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Toxicological evaluation of advanced glycation end product Nε-(carboxymethyl)lysine: Acute and subacute oral toxicity studies

Cited by 40 publications

References 46 publications

The Impact of Different Drying Techniques and Controlled Storage on the Development of Advanced Glycation End Products in Skim Milk Powders Using Isotope Dilution ESI-LC-MS/MS

The Impact of Different Drying Techniques and Controlled Storage on the Development of Advanced Glycation End Products in Skim Milk Powders Using Isotope Dilution ESI-LC-MS/MS

Accumulation and effects of dietary advanced glycation end products on the gastrointestinal tract in rats

Maillard Reactions – An Important Factor of the Safety and Quality of Infant Formula

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