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Article ; Online: Disruption of the Molecular Regulation of Mitochondrial Metabolism in Airway and Lung Epithelial Cells by Cigarette Smoke: Are Aldehydes the Culprit?

Tulen, Christy B M / Opperhuizen, Antoon / van Schooten, Frederik-Jan / Remels, Alexander H V

2023 Volume 12, Issue 2

Abstract: Chronic obstructive pulmonary disease (COPD) is a devastating lung disease for which cigarette smoking is the main risk factor. Acetaldehyde, acrolein, and formaldehyde are short-chain aldehydes known to be formed during pyrolysis and combustion of ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is a devastating lung disease for which cigarette smoking is the main risk factor. Acetaldehyde, acrolein, and formaldehyde are short-chain aldehydes known to be formed during pyrolysis and combustion of tobacco and have been linked to respiratory toxicity. Mitochondrial dysfunction is suggested to be mechanistically and causally involved in the pathogenesis of smoking-associated lung diseases such as COPD. Cigarette smoke (CS) has been shown to impair the molecular regulation of mitochondrial metabolism and content in epithelial cells of the airways and lungs. Although it is unknown which specific chemicals present in CS are responsible for this, it has been suggested that aldehydes may be involved. Therefore, it has been proposed by the World Health Organization to regulate aldehydes in commercially-available cigarettes. In this review, we comprehensively describe and discuss the impact of acetaldehyde, acrolein, and formaldehyde on mitochondrial function and content and the molecular pathways controlling this (biogenesis versus mitophagy) in epithelial cells of the airways and lungs. In addition, potential therapeutic applications targeting (aldehyde-induced) mitochondrial dysfunction, as well as regulatory implications, and the necessary required future studies to provide scientific support for this regulation, have been covered in this review.
MeSH term(s)	Nicotiana/adverse effects ; Aldehydes/metabolism ; Acrolein/toxicity ; Acrolein/metabolism ; Cigarette Smoking/adverse effects ; Lung/pathology ; Pulmonary Disease, Chronic Obstructive/pathology ; Epithelial Cells/metabolism ; Formaldehyde ; Acetaldehyde/toxicity ; Acetaldehyde/metabolism ; Mitochondria/metabolism
Chemical Substances	Aldehydes ; Acrolein (7864XYD3JJ) ; Formaldehyde (1HG84L3525) ; Acetaldehyde (GO1N1ZPR3B)
Language	English
Publishing date	2023-01-12
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12020299
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Habitual Intake of Dietary Dicarbonyls is Associated with Greater Insulin Sensitivity and Lower Prevalence of Type 2 Diabetes: The Maastricht Study.

Maasen, Kim / Eussen, Simone J P M / Dagnelie, Pieter C / Stehouwer, Coen D A / Opperhuizen, Antoon / van Greevenbroek, Marleen M J / Schalkwijk, Casper G

The American journal of clinical nutrition

2023 Volume 118, Issue 1, Page(s) 151–161

Abstract: Background: Dicarbonyls are reactive precursors of advanced glycation end-products (AGEs). Dicarbonyls are formed endogenously, but also during food processing. Circulating dicarbonyls are positively associated with insulin resistance and type 2 ... ...

Abstract	Background: Dicarbonyls are reactive precursors of advanced glycation end-products (AGEs). Dicarbonyls are formed endogenously, but also during food processing. Circulating dicarbonyls are positively associated with insulin resistance and type 2 diabetes, but the consequences of dietary dicarbonyls are unknown. Objectives: We aimed to examine the associations of dietary intake of dicarbonyls with insulin sensitivity, β-cell function, and the prevalence of prediabetes or type 2 diabetes. Methods: In 6282 participants (aged 60 ± 9 y; 50% men, 23% type 2 diabetes [oversampled]) of the population-based cohort the Maastricht Study, we estimated the habitual intake of the dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) using food frequency questionnaires. Insulin sensitivity (n = 2390), β-cell function (n = 2336), and glucose metabolism status (n = 6282) were measured by a 7-point oral glucose tolerance test. Insulin sensitivity was assessed as the Matsuda index. Additionally, insulin sensitivity was measured as HOMA2-IR (n = 2611). β-cell function was assessed as the C-peptidogenic index, overall insulin secretion, glucose sensitivity, potentiation factor, and rate sensitivity. Cross-sectional associations of dietary dicarbonyls with these outcomes were investigated using linear or logistic regression adjusting for age, sex, cardiometabolic risk factors, lifestyle, and dietary factors. Results: Higher dietary MGO and 3-DG intakes were associated with greater insulin sensitivity after full adjustment, indicated by both a higher Matsuda index (MGO: Std. β [95% CI] = 0.08 [0.04, 0.12]; 3-DG: 0.09 [0.05, 0.13]) and a lower HOMA2-IR (MGO: Std. β = -0.05 [-0.09, -0.01]; 3-DG: -0.04 [-0.08, -0.01]). Moreover, higher MGO and 3-DG intakes were associated with a lower prevalence of newly diagnosed type 2 diabetes (OR [95% CI] = 0.78 [0.65, 0.93] and 0.81 [0.66, 0.99]). There were no consistent associations of MGO, GO, and 3-DG intakes with β-cell function. Conclusion: Higher habitual consumption of the dicarbonyls MGO and 3-DG was associated with better insulin sensitivity and lower prevalence of type 2 diabetes, after excluding individuals with known diabetes. These novel observations warrant further exploration in prospective cohorts and intervention studies.
MeSH term(s)	Female ; Humans ; Male ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/etiology ; Glyoxal ; Insulin Resistance ; Magnesium Oxide ; Prevalence ; Prospective Studies ; Pyruvaldehyde
Chemical Substances	Glyoxal (50NP6JJ975) ; Magnesium Oxide (3A3U0GI71G) ; Pyruvaldehyde (722KLD7415)
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.1016/j.ajcnut.2023.04.011
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Article ; Online: Impact of More Intense Smoking Parameters and Flavor Variety on Toxicant Levels in Emissions of a Heated Tobacco Product.

Davigo, Michele / Klerx, Walther N M / van Schooten, Frederik-Jan / Opperhuizen, Antoon / Remels, Alexander H V / Talhout, Reinskje

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

2023 Volume 26, Issue 5, Page(s) 571–579

Abstract: Introduction: IQOS HEETS are promoted as reduced-risk alternatives to cigarettes. Although some studies have investigated the chemical composition of HEETS emissions, little is known on whether toxicant levels in such emissions are affected by different ...

Abstract	Introduction: IQOS HEETS are promoted as reduced-risk alternatives to cigarettes. Although some studies have investigated the chemical composition of HEETS emissions, little is known on whether toxicant levels in such emissions are affected by different puffing parameters and flavor varieties. This has important implications when assessing actual human exposure, since IQOS users develop a specific and personalized puffing behavior and may use different HEETS variants. Methods: This study measured the levels of nicotine, total particulate matter, carbonyl compounds, and tobacco-specific nitrosamines (TSNAs) in the emissions of nine differently flavored HEETS and two cigarettes (1R6F and Marlboro Red, MR). Emissions from Yellow HEETS, 1R6F, and MR were collected using the World Health Organization Intense smoking regime and four more intense smoking regimes. Results: Yellow HEETS aerosol contained lower levels of toxicants compared to 1R6F and MR smoke. More intense smoking regimes increased carbonyl release in cigarette smoke, whereas only higher puff frequency led to lower levels of toxicants in Yellow HEETS aerosol. Some HEETS varieties exhibited higher levels of formaldehyde and TSNAs in their aerosols compared to Yellow HEETS. Conclusions: Puff frequency was identified as the only smoking parameter that significantly lowered the release of almost all toxicants in Yellow HEETS, whereas a combination of higher puff volume and puff duration led to increased levels of some carbonyls. Differences in toxicant levels between various commercially available HEETS have important implications when assessing their health impact, as their consumption might induce different toxicant exposure and health effects. Implications: HEETS release about half as much nicotine and substantially lower levels of toxicants compared to cigarettes. Literature data showed that puffing intensity is increased in cigarette smokers switching to HEETS, maybe in reaction to these lower nicotine levels. Our results show a differential impact of increased puff frequency, puff duration, and puff volume in the release of toxicants from HEETS. Thus, industry-independent studies on puff topography are critical to make choices for the most relevant puffing regime for heated tobacco product regulation. Regulators should consider evaluating the health impact of multiple HEETS varieties, as the tobacco filler composition significantly affects the release of certain toxicants.
MeSH term(s)	Tobacco Products/analysis ; Flavoring Agents/analysis ; Humans ; Nicotine/analysis ; Particulate Matter/analysis ; Nitrosamines/analysis ; Nicotiana/chemistry ; Aerosols/analysis ; Smoke/analysis ; Smoking
Chemical Substances	Flavoring Agents ; Nicotine (6M3C89ZY6R) ; Particulate Matter ; Nitrosamines ; Aerosols ; Smoke
Language	English
Publishing date	2023-11-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1452315-2
ISSN	1469-994X ; 1462-2203
ISSN (online)	1469-994X
ISSN	1462-2203
DOI	10.1093/ntr/ntad238
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Article ; Online: Alterations in the molecular control of mitochondrial turnover in COPD lung and airway epithelial cells.

Tulen, Christy B M / van de Wetering, Cheryl / Schiffers, Caspar H J / Weltjens, Ellen / Benedikter, Birke J / Leermakers, Pieter A / Boukhaled, Juliana H / Drittij, Marie-José / Schmeck, Bernd T / Reynaert, Niki L / Opperhuizen, Antoon / van Schooten, Frederik-Jan / Remels, Alexander H V

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4821

Abstract: Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover ( ... ...

Abstract	Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover (mitochondrial biogenesis vs mitophagy) are involved. Therefore, in this study, the abundance of key molecules controlling mitochondrial turnover were assessed in peripheral lung tissue from non-COPD patients (n = 6) and COPD patients (n = 11; GOLDII n = 4/11; GOLDIV n = 7/11) and in both undifferentiated and differentiated human primary bronchial epithelial cells (PBEC) from non-COPD patients and COPD patients (n = 4-7 patients/group). We observed significantly decreased transcript levels of key molecules controlling mitochondrial biogenesis (PPARGC1B, PPRC1, PPARD) in peripheral lung tissue from severe COPD patients. Interestingly, mRNA levels of the transcription factor TFAM (mitochondrial biogenesis) and BNIP3L (mitophagy) were increased in these patients. In general, these alterations were not recapitulated in undifferentiated and differentiated PBECs with the exception of decreased PPARGC1B expression in both PBEC models. Although these findings provide valuable insight in these pathways in bronchial epithelial cells and peripheral lung tissue of COPD patients, whether or not these alterations contribute to COPD pathogenesis, underlie changes in mitochondrial function or may represent compensatory mechanisms remains to be established.
MeSH term(s)	Humans ; Lung/pathology ; Pulmonary Disease, Chronic Obstructive/pathology ; Mitochondrial Turnover ; Mitochondria/metabolism ; Epithelial Cells/metabolism ; RNA-Binding Proteins/metabolism
Chemical Substances	PPARGC1B protein, human ; RNA-Binding Proteins
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55335-8
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Article: Dietary Advanced Glycation Endproducts and the Gastrointestinal Tract

van der Lugt, Timme / Opperhuizen, Antoon / Bast, Aalt / Vrolijk, Misha F

Nutrients. 2020 Sept. 14, v. 12, no. 9

2020

Abstract: The prevalence of inflammatory bowel diseases (IBD) is increasing in the world. The introduction of the Western diet has been suggested as a potential explanation of increased prevalence. The Western diet includes highly processed food products, and ... ...

Abstract	The prevalence of inflammatory bowel diseases (IBD) is increasing in the world. The introduction of the Western diet has been suggested as a potential explanation of increased prevalence. The Western diet includes highly processed food products, and often include thermal treatment. During thermal treatment, the Maillard reaction can occur, leading to the formation of dietary advanced glycation endproducts (dAGEs). In this review, different biological effects of dAGEs are discussed, including their digestion, absorption, formation, and degradation in the gastrointestinal tract, with an emphasis on their pro-inflammatory effects. In addition, potential mechanisms in the inflammatory effects of dAGEs are discussed. This review also specifically elaborates on the involvement of the effects of dAGEs in IBD and focuses on evidence regarding the involvement of dAGEs in the symptoms of IBD. Finally, knowledge gaps that still need to be filled are identified.
Keywords	Maillard reaction ; Western diets ; absorption ; advanced glycation end products ; degradation ; digestion ; digestive tract ; glycation ; heat treatment ; knowledge ; prevalence ; processed foods
Language	English
Dates of publication	2020-0914
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu12092814
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Haemodynamic effects of the flavonoid quercetin in rats revisited.

Vrolijk, Misha F / van Essen, Helma / Opperhuizen, Antoon / Bast, Aalt / Janssen, Ben J

British journal of pharmacology

2020 Volume 177, Issue 8, Page(s) 1841–1852

Abstract: Background and purpose: The flavonoid quercetin increased the in vitro potency of the α: Experimental approach: First, in rats pretreated with quercetin or its vehicle, responses to phenylephrine and tamsulosin were examined. Second, tamsulosin- ... ...

Abstract	Background and purpose: The flavonoid quercetin increased the in vitro potency of the α Experimental approach: First, in rats pretreated with quercetin or its vehicle, responses to phenylephrine and tamsulosin were examined. Second, tamsulosin-induced changes in renal, mesenteric, hindquarter and carotid conductance were compared in quercetin- and vehicle-treated rats instrumented with Doppler flow probes. Animals were also placed on a tilt table to record regional haemodynamic changes to orthostatic challenges. Third, adult SHR were instrumented with telemeters to measure 24-hr patterns of BP. Recordings were made before and during a 5-week oral treatment of quercetin. Finally, pre-hypertensive SHR were treated with quercetin from 4 to 8 weeks of age and arterial pressure was measured at 8 and 12 weeks. Key results: Pretreatment with quercetin did not influence the responses to phenylephrine and tamsulosin, in neither WKY nor SHR. While tamsulosin treatment and tilting lowered BP and increased conductance in all vascular beds, effect size was not influenced by pretreatment with quercetin. Prolonged treatment with quercetin, in either prehypertensive SHR or adult SHR with established hypertension did not lower BP. Conclusions and implications: Cumulatively, these data demonstrate that quercetin does not amplify haemodynamic effects of tamsulosin or tilting in vivo in rats and has no effect on BP development in SHR.
MeSH term(s)	Animals ; Blood Pressure ; Flavonoids ; Hemodynamics ; Hypertension/drug therapy ; Quercetin/pharmacology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY
Chemical Substances	Flavonoids ; Quercetin (9IKM0I5T1E)
Language	English
Publishing date	2020-02-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.14955
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Article ; Online: Dietary Advanced Glycation Endproducts and the Gastrointestinal Tract.

van der Lugt, Timme / Opperhuizen, Antoon / Bast, Aalt / Vrolijk, Misha F

Nutrients

2020 Volume 12, Issue 9

Abstract	The prevalence of inflammatory bowel diseases (IBD) is increasing in the world. The introduction of the Western diet has been suggested as a potential explanation of increased prevalence. The Western diet includes highly processed food products, and often include thermal treatment. During thermal treatment, the Maillard reaction can occur, leading to the formation of dietary advanced glycation endproducts (dAGEs). In this review, different biological effects of dAGEs are discussed, including their digestion, absorption, formation, and degradation in the gastrointestinal tract, with an emphasis on their pro-inflammatory effects. In addition, potential mechanisms in the inflammatory effects of dAGEs are discussed. This review also specifically elaborates on the involvement of the effects of dAGEs in IBD and focuses on evidence regarding the involvement of dAGEs in the symptoms of IBD. Finally, knowledge gaps that still need to be filled are identified.
MeSH term(s)	Diet, Western/adverse effects ; Dietary Proteins/metabolism ; Gastrointestinal Tract/drug effects ; Glycation End Products, Advanced/metabolism ; Humans ; Inflammatory Bowel Diseases/epidemiology ; Inflammatory Bowel Diseases/etiology ; Maillard Reaction/drug effects ; Prevalence
Chemical Substances	Dietary Proteins ; Glycation End Products, Advanced
Language	English
Publishing date	2020-09-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu12092814
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Article ; Online: Dietary Advanced Glycation Endproducts Decrease Glucocorticoid Sensitivity In Vitro.

van der Lugt, Timme / Weseler, Antje R / Vrolijk, Misha F / Opperhuizen, Antoon / Bast, Aalt

Nutrients

2020 Volume 12, Issue 2

Abstract: Glucocorticoids are very effective anti-inflammatory drugs and widely used for inflammatory bowel disease (IBD) patients. However, approximately 20% of IBD patients do not respond to glucocorticoids and the reason for this is largely unknown. Dietary ... ...

Abstract	Glucocorticoids are very effective anti-inflammatory drugs and widely used for inflammatory bowel disease (IBD) patients. However, approximately 20% of IBD patients do not respond to glucocorticoids and the reason for this is largely unknown. Dietary advanced glycation endproducts (AGEs) are formed via the Maillard reaction during the thermal processing of food products and can induce a pro-inflammatory reaction in human cells. To investigate whether this pro-inflammatory response could be mitigated by glucocorticoids, human macrophage-like cells were exposed to both LPS and AGEs to induce interleukin-8 (IL8) secretion. This pro-inflammatory response was then modulated by adding pharmacological compounds interfering in different steps of the anti-inflammatory mechanism of glucocorticoids: rapamycin, quercetin, and theophylline. Additionally, intracellular reactive oxygen species (ROS) were measured and the glucocorticoid receptor phosphorylation state was assessed. The results show that AGEs induced glucocorticoid resistance, which could be mitigated by quercetin and rapamycin. No change in the phosphorylation state of the glucocorticoid receptor was observed. Additionally, intracellular ROS formation was induced by AGEs, which was mitigated by quercetin. This suggests that AGE-induced ROS is an underlying mechanism to AGE-induced glucocorticoid resistance. This study shows for the first time the phenomenon of dietary AGE-induced glucocorticoid resistance due to the formation of ROS. Our findings indicate that food products with a high inflammatory potential can induce glucocorticoid resistance; these results may be of great importance to IBD patients suffering from glucocorticoid resistance.
MeSH term(s)	Drug Resistance/drug effects ; Glucocorticoids/pharmacology ; Glucocorticoids/therapeutic use ; Glycation End Products, Advanced/adverse effects ; Humans ; Inflammation ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/metabolism ; Interleukin-8/metabolism ; Macrophages/metabolism ; Maillard Reaction ; Phosphorylation ; Reactive Oxygen Species/metabolism ; Receptors, Glucocorticoid/metabolism ; THP-1 Cells
Chemical Substances	Glucocorticoids ; Glycation End Products, Advanced ; Interleukin-8 ; Reactive Oxygen Species ; Receptors, Glucocorticoid
Language	English
Publishing date	2020-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu12020441
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Article: Maternal fatty acid status during pregnancy versus offspring inflammatory markers: a canonical correlation analysis of the MEFAB cohort.

Rouschop, Sven H / Smolinska, Agnieszka / Gielen, Marij / de Groot, Renate H M / Zeegers, Maurice P / Opperhuizen, Antoon / van Schooten, Frederik J / Godschalk, Roger W

Frontiers in nutrition

2023 Volume 10, Page(s) 1264278

Abstract: The development of inflammatory lung disorders in children may be related to maternal fatty acid intake during pregnancy. We therefore examined maternal fatty acid (FA) status during pregnancy and its associations with inflammatory markers and lung ... ...

Abstract	The development of inflammatory lung disorders in children may be related to maternal fatty acid intake during pregnancy. We therefore examined maternal fatty acid (FA) status during pregnancy and its associations with inflammatory markers and lung conditions in the child by analyzing data from the MEFAB cohort using multivariate canonical correlation analysis (CCA). In the MEFAB cohort, 39 different phospholipid FAs were measured in maternal plasma at 16, 22 and 32 weeks of pregnancy, and at day of birth. Child inflammatory markers and self-reported doctor diagnosis of inflammatory lung disorders were assessed at 7 years of age. Using CCA, we found that maternal FA levels during pregnancy were significantly associated with child inflammatory markers at 7 years of age and that Mead acid (20:3n-9) was the most important FA for this correlation. To further verify the importance of Mead acid, we examined the relation between maternal Mead acid levels at the day of birth with the development of inflammatory lung disorders in children at age 7. After stratification for the child's sex, maternal Mead acid levels at day of birth were significantly related with self-reported doctor diagnosis of asthma and lung infections in boys, and bronchitis and total number of lung disorders in girls. Future studies should investigate whether the importance of Mead acid in the relation between maternal FA status and inflammation and lung disorders in the child is due to its role as biomarker for essential fatty acid deficiency or due to its own biological function as pro-inflammatory mediator.
Language	English
Publishing date	2023-10-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2023.1264278
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Article: Gastrointestinal digestion of dietary advanced glycation endproducts using an in vitro model of the gastrointestinal tract (TIM-1)

van der Lugt, Timme / Venema, Koen / van Leeuwen, Stefan / Vrolijk, Misha F / Opperhuizen, Antoon / Bast, Aalt

Food & function. 2020 July 22, v. 11, no. 7

2020

Abstract: Protein- and sugar-rich food products processed at high temperatures contain large amounts of dietary advanced glycation endproducts (dAGEs). Our earlier studies have shown that specifically protein-bound dAGEs induce a pro-inflammatory reaction in human ...

Abstract	Protein- and sugar-rich food products processed at high temperatures contain large amounts of dietary advanced glycation endproducts (dAGEs). Our earlier studies have shown that specifically protein-bound dAGEs induce a pro-inflammatory reaction in human macrophage-like cells. To what extent these protein-bound dAGEs survive the human gastrointestinal (GI) tract is still unclear. In this study we analysed gastric and small intestinal digestion of dAGEs using the validated, standardised TNO in vitro gastroIntestinal digestion model (TIM-1), a dynamic in vitro model which mimics the upper human GI tract. This model takes multiple parameters into account, such as: dynamic pH curves, peristaltic mixing, addition of bile and pancreatic digestive enzymes, and passive absorption. Samples of different digested food products were collected at different time points after (i) only gastric digestion and (ii) after both gastric plus small intestinal digestion. Samples were analysed for dAGEs using UPLC-MS/MS for the lysine derived Nᵋ-carboxymethyllysine (CML) and Nᵋ-carboxyethyllysine (CEL), and the arginine derived methylglyoxal-derived hydroimidazolone-1 (MG-H1), and glyoxal-derived hydroimidazolone-1 (G-H1). All AGEs were quantified in their protein-bound and free form. The results of this in vitro study show that protein-bound dAGEs survive gastrointestinal digestion and are additionally formed during small intestinal digestion. In ginger biscuits, the presence MG-H1 in the GI tract increased with more than 400%. This also indicates that dAGEs enter the human GI tract with potential pro-inflammatory characteristics.
Keywords	absorption ; advanced glycation end products ; arginine ; bile ; biscuits ; cells ; digestion ; digestive enzymes ; ginger ; humans ; in vitro digestion ; in vitro studies ; intestines ; lysine ; mixing ; models ; pH ; sampling ; temperature
Language	English
Dates of publication	2020-0722
Size	p. 6297-6307.
Publishing place	The Royal Society of Chemistry
Document type	Article
Note	NAL-light
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d0fo00450b
Database	NAL-Catalogue (AGRICOLA)

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