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Gong Y, Zhou T, Ma R, Yang J, Zhao Y, Pan M, Huang Z, Wen H, Jiang H, Wang J. Efficacy and mechanism of energy metabolism dual-regulated nanoparticles (atovaquone-albendazole nanoparticles) against cystic echinococcosis. BMC Infect Dis 2024; 24:778. [PMID: 39097707 PMCID: PMC11297608 DOI: 10.1186/s12879-024-09662-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 07/24/2024] [Indexed: 08/05/2024] Open
Abstract
BACKGROUND Albendazole (ABZ) and atovaquone (ATO) achieve killing efficacy on Echinococcus granulosus (Egs) by inhibiting energy metabolism, but their utilization rate is low. This study aims to analyze the killing efficacy of ABZ-ATO loading nanoparticles (ABZ-ATO NPs) on Egs. METHODS Physicochemical properties of NPs were evaluated by ultraviolet spectroscopy and nanoparticle size potentiometer. In vitro experiments exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on protoscolex activity, drug toxicity on liver cell LO2, ROS production, and energy metabolism indexes (lactic dehydrogenase, lactic acid, pyruvic acid, and ATP). In vivo of Egs-infected mouse model exmianed the efficacy of ATO, ABZ, or ATO-ABZ NPs on vesicle growth and organ toxicity. RESULTS Drug NPs are characterized by uniform particle size, stability, high drug loading, and - 21.6mV of zeta potential. ABZ or ATO NPs are more potent than free drugs in inhibiting protoscolex activity. The protoscolex-killing effect of ATO-ABZ NPs was stronger than that of free drugs. In vivo Egs-infected mice experiment showed that ATO-ABZ NPs reduced vesicle size and could protect various organs. The results of energy metabolism showed that ATO-ABZ NPs significantly increased the ROS level and pyruvic acid content, and decreased lactate dehydrogenase, lactic acid content, and ATP production in the larvae. In addition, ATO-ABZ NPs promoted a decrease in DHODH protein expression in protoscolexes. CONCLUSION ATO-ABZ NPs exhibits anti-CE in vitro and in vivo, possibly by inhibiting energy production and promoting pyruvic acid aggregation.
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Affiliation(s)
- Yuehong Gong
- First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
- Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Clinical Drug Research, Urumqi, Xinjiang, 830011, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Tianjiao Zhou
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China
| | - Ruijia Ma
- Pharmacy Department, Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Jianhua Yang
- First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
- Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Clinical Drug Research, Urumqi, Xinjiang, 830011, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Yicong Zhao
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China
- College of Pharmaceutical Sciences, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Meichi Pan
- College of Pharmaceutical Sciences, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Zhangjian Huang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
- College of Pharmaceutical Sciences, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China
| | - Hao Wen
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
| | - Hulin Jiang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
| | - Jianhua Wang
- First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
- Department of Pharmacy, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Clinical Drug Research, Urumqi, Xinjiang, 830011, China.
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
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Mildner-Szkudlarz S, Barbara Różańska M, Siger A, Zembrzuska J, Szwengiel A. Formation of Maillard reaction products in a model bread system of different gluten-free flours. Food Chem 2023; 429:136994. [PMID: 37517228 DOI: 10.1016/j.foodchem.2023.136994] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 07/19/2023] [Accepted: 07/23/2023] [Indexed: 08/01/2023]
Abstract
In this study, we determined the levels of Maillard-type products (furosine, free fluorescent advanced glycation end products, 3-deoxyglucosone, methylglyoxal, and N-ε-carboxymethyllysine) in a model gluten-free bread made of wholegrain white, brown, wild, red, and black rice flour, as well as of yellow and purple corn flour. The total protein, lysine, arginine, and cysteine contents were found to relate directly to the formation of Maillard-type products. The malvidin, ferulic, syringic, sinapic, and p-coumaric acids present in gluten-free breads were effective against the formation of furosine, fluorescent compounds, and dicarbonyls, but were ineffective in mitigating CML. Although the bread formulated with purple corn flour had the lowest levels of furosine and fluorescent compounds, this formulation led to an increase in N-ε-carboxymethyllysine and adversely affected the bread's aroma, on account of the presence of polyphenols responsible for a bitter aroma, which were at their highest concentration (1942.34 µg/g) in this bread.
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Affiliation(s)
- Sylwia Mildner-Szkudlarz
- Department of Food Technology of Plant Origin, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, Wojska Polskiego 28, 60-637 Poznań, Poland.
| | - Maria Barbara Różańska
- Department of Food Technology of Plant Origin, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, Wojska Polskiego 28, 60-637 Poznań, Poland
| | - Aleksander Siger
- Department of Biochemistry and Food Analysis, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, Wojska Polskiego 28, 60-637 Poznań, Poland
| | - Joanna Zembrzuska
- Institute of Chemistry and Technical Electrochemistry, Faculty of Chemical Technology, Poznan University of Technology, Berdychowo 4, 60-965 Poznan, Poland
| | - Artur Szwengiel
- Department of Food Technology of Plant Origin, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, Wojska Polskiego 28, 60-637 Poznań, Poland
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Sun J, Akıllıoğlu HG, Zhong J, Muk T, Pan X, Lund MN, Sangild PT, Nguyen DN, Bering SB. Ultra-High Temperature Treatment of Liquid Infant Formula, Systemic Immunity, and Kidney Development in Preterm Neonates. Mol Nutr Food Res 2023; 67:e2300318. [PMID: 37888862 DOI: 10.1002/mnfr.202300318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/25/2023] [Indexed: 10/28/2023]
Abstract
SCOPE Ready-to-feed liquid infant formulas (IFs) are increasingly being used for newborn preterm infants when human milk is unavailable. However, sterilization of liquid IFs by ultra-high temperature (UHT) introduces Maillard reaction products (MRPs) that may negatively affect systemic immune and kidney development. METHODS AND RESULTS UHT-treated IF without and with prolonged storage (SUHT) are tested against pasteurized IF (PAST) in newborn preterm pigs as a model for preterm infants. After 5 days, blood leukocytes, markers of systemic immunity and inflammation, kidney structure and function are evaluated. No consistent differences between UHT and PAST pigs are observed. However, SUHT increases plasma TNFα and IL-6 and reduces neutrophils and in vitro response to LPS. In SUHT pigs, the immature kidneys show minor upregulation of gene expressions related to inflammation (RAGE, MPO, MMP9) and oxidative stress (CAT, GLO1), together with glomerular mesangial expansion and cell injury. The increased inflammatory status in SUHT pigs appears unrelated to systemic levels of MRPs. CONCLUSION SUHT feeding may impair systemic immunity and affect kidney development in preterm newborns. The systemic effects may be induced by local gut inflammatory effects of MRPs. Optimal processing and length of storage are critical for UHT-treated liquid IFs for preterm infants.
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Affiliation(s)
- Jing Sun
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
| | | | - Jingren Zhong
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
| | - Tik Muk
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
| | - Xiaoyu Pan
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
| | - Marianne Nissen Lund
- Department of Food Science, University of Copenhagen, Denmark
- Department of Biomedical Sciences, University of Copenhagen, Denmark
| | - Per Torp Sangild
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
- Hans Christian Andersen Children's Hospital, Odense, Denmark
- Department of Neonatology, Rigshospitalet, Denmark
| | - Duc Ninh Nguyen
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
| | - Stine Brandt Bering
- Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark
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Khan MI, Ashfaq F, Alsayegh AA, Hamouda A, Khatoon F, Altamimi TN, Alhodieb FS, Beg MMA. Advanced glycation end product signaling and metabolic complications: Dietary approach. World J Diabetes 2023; 14:995-1012. [PMID: 37547584 PMCID: PMC10401445 DOI: 10.4239/wjd.v14.i7.995] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 04/08/2023] [Accepted: 04/27/2023] [Indexed: 07/12/2023] Open
Abstract
Advanced glycation end products (AGEs) are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions. The modern western diet is full of heat-treated foods that contribute to AGE intake. Foods high in AGEs in the contemporary diet include processed cereal products. Due to industrialization and marketing strategies, restaurant meals are modified rather than being traditionally or conventionally cooked. Fried, grilled, baked, and boiled foods have the greatest AGE levels. Higher AGE-content foods include dry nuts, roasted walnuts, sunflower seeds, fried chicken, bacon, and beef. Animal proteins and processed plant foods contain furosine, acrylamide, heterocyclic amines, and 5-hydroxymethylfurfural. Furosine (2-furoil-methyl-lysine) is an amino acid found in cooked meat products and other processed foods. High concentrations of carboxymethyl-lysine, carboxyethyl-lysine, and methylglyoxal-O are found in heat-treated nonvegetarian foods, peanut butter, and cereal items. Increased plasma levels of AGEs, which are harmful chemicals that lead to age-related diseases and physiological aging, diabetes, and autoimmune/inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. AGEs in the pathophysiology of metabolic diseases have been linked to individuals with diabetes mellitus who have peripheral nerves with high amounts of AGEs and diabetes has been linked to increased myelin glycation. Insulin resistance and hyperglycemia can impact numerous human tissues and organs, leading to long-term difficulties in a number of systems and organs, including the cardiovascular system. Plasma AGE levels are linked to all-cause mortality in individuals with diabetes who have fatal or nonfatal coronary artery disease, such as ventricular dysfunction. High levels of tissue AGEs are independently associated with cardiac systolic dysfunction in diabetic patients with heart failure compared with diabetic patients without heart failure. It is widely recognized that AGEs and oxidative stress play a key role in the cardiovascular complications of diabetes because they both influence and are impacted by oxidative stress. All chronic illnesses involve protein, lipid, or nucleic acid modifications including crosslinked and nondegradable aggregates known as AGEs. Endogenous AGE formation or dietary AGE uptake can result in additional protein modifications and stimulation of several inflammatory signaling pathways. Many of these systems, however, require additional explanation because they are not entirely obvious. This review summarizes the current evidence regarding dietary sources of AGEs and metabolism-related complications associated with AGEs.
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Affiliation(s)
- Mohammad Idreesh Khan
- Department of Clinical Nutrition, College of Applied Health Sciences in Ar Rass, Qassim University, Ar Rass 51921, Saudi Arabia
| | - Fauzia Ashfaq
- Clinical Nutrition Department, Applied Medical Sciences College, Jazan University, Jazan 82817, Saudi Arabia
| | - Abdulrahman A Alsayegh
- Clinical Nutrition Department, Applied Medical Sciences College, Jazan University, Jazan 82817, Saudi Arabia
| | - Alshaimaa Hamouda
- Clinical Nutrition Department, Applied Medical Sciences College, Jazan University, Jazan 82817, Saudi Arabia
| | - Fahmida Khatoon
- Department of Biochemistry, College of Medicine, University of Hail, Hail 2240, Saudi Arabia
| | - Tahani Nasser Altamimi
- Department of Family and Community Medicine, College of Medicine, University of Hail, Hail 2240, Saudi Arabia
| | - Fahad Saad Alhodieb
- Department of Clinical Nutrition, College of Applied Health Sciences in Ar Rass, Qassim University, Ar Rass 51921, Saudi Arabia
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Steenbeke M, Speeckaert R, Desmedt S, Glorieux G, Delanghe JR, Speeckaert MM. The Role of Advanced Glycation End Products and Its Soluble Receptor in Kidney Diseases. Int J Mol Sci 2022; 23:ijms23073439. [PMID: 35408796 PMCID: PMC8998875 DOI: 10.3390/ijms23073439] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 03/20/2022] [Accepted: 03/21/2022] [Indexed: 02/06/2023] Open
Abstract
Patients with chronic kidney disease (CKD) are more prone to oxidative stress and chronic inflammation, which may lead to an increase in the synthesis of advanced glycation end products (AGEs). Because AGEs are mostly removed by healthy kidneys, AGE accumulation is a result of both increased production and decreased kidney clearance. On the other hand, AGEs may potentially hasten decreasing kidney function in CKD patients, and are independently related to all-cause mortality. They are one of the non-traditional risk factors that play a significant role in the underlying processes that lead to excessive cardiovascular disease in CKD patients. When AGEs interact with their cell-bound receptor (RAGE), cell dysfunction is initiated by activating nuclear factor kappa-B (NF-κB), increasing the production and release of inflammatory cytokines. Alterations in the AGE-RAGE system have been related to the development of several chronic kidney diseases. Soluble RAGE (sRAGE) is a decoy receptor that suppresses membrane-bound RAGE activation and AGE-RAGE-related toxicity. sRAGE, and more specifically, the AGE/sRAGE ratio, may be promising tools for predicting the prognosis of kidney diseases. In the present review, we discuss the potential role of AGEs and sRAGE as biomarkers in different kidney pathologies.
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Affiliation(s)
- Mieke Steenbeke
- Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Ghent, Belgium; (M.S.); (S.D.); (G.G.)
| | - Reinhart Speeckaert
- Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium;
- Research Foundation Flanders, 1000 Brussels, Belgium
| | - Stéphanie Desmedt
- Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Ghent, Belgium; (M.S.); (S.D.); (G.G.)
| | - Griet Glorieux
- Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Ghent, Belgium; (M.S.); (S.D.); (G.G.)
| | - Joris R. Delanghe
- Department of Diagnostic Sciences, Ghent University, 9000 Ghent, Belgium;
| | - Marijn M. Speeckaert
- Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Ghent, Belgium; (M.S.); (S.D.); (G.G.)
- Research Foundation Flanders, 1000 Brussels, Belgium
- Correspondence:
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Li HY, Yang HG, Wu HM, Yao QQ, Zhang ZY, Meng QS, Fan LL, Wang JQ, Zheng N. Inhibitory effects of lactoferrin on pulmonary inflammatory processes induced by lipopolysaccharide by modulating the TLR4-related pathway. J Dairy Sci 2021; 104:7383-7392. [PMID: 33838887 DOI: 10.3168/jds.2020-19232] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 02/24/2021] [Indexed: 11/19/2022]
Abstract
This study tested the ability of lactoferrin to modulate pulmonary inflammation. To construct in vitro and in vivo inflammatory lung models, cells from the human lung adenocarcinoma cell line (A549) were exposed to lipopolysaccharide (LPS, 1 µg/mL), and mice (CD-1) were intratracheally administered LPS [10 mg/kg of body weight (BW), tracheal lumen injection], respectively. The A549 cells were preincubated with lactoferrin (10 mg/mL), and the mice were intraperitoneally injected with lactoferrin (100 mg/kg of BW), followed by LPS treatment. The concentrations of proinflammatory cytokines (IL-1β and TNF-α) in culture medium of A549 cells and in bronchoalveolar lavage fluid of the mice were determined using enzyme-linked immunosorbent assays. The toll-like receptor 4-related pathway (TLR4/MyD88/IRAK1/TRAF6/NFκB) was determined at gene and protein expression levels in A549 cells and mouse lung tissue. Results showed that LPS treatment significantly elevated the concentrations of IL-1β and TNF-α in the A549 cell culture medium and in bronchoalveolar lavage fluid of the mice; it also elevated both the mRNA and protein expressions of TLR4 and the TLR4 downstream factors in A549 cells and mouse lung tissue. Nevertheless, lactoferrin apparently depressed the releases of IL-1β and TNF-α from A549 cells and lung tissues stimulated by LPS, and significantly suppressed the TLR4 signaling pathway. Lactoferrin also promoted the enhancement of miR-146a expression in A549 cells and mouse lung tissue. Moreover, 100°C heating for 3 min caused total loss of the previously listed bioactivity of lactoferrin. Collectively, we proved that lactoferrin intervened in LPS-induced inflammation in the pulmonary cell model and in the mouse model, through inhibiting the TLR4-related pathway.
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Affiliation(s)
- H Y Li
- Key Laboratory of Quality and Safety Control for Milk and Dairy Products, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - H G Yang
- Sericultural and Agri-Food Research Institute, Guangdong Academy of Agricultural Sciences, Key Laboratory of Functional Foods, Ministry of Agriculture and Rural Affairs, Guangzhou 510610, P. R. China
| | - H M Wu
- Key Laboratory of Quality and Safety Control for Milk and Dairy Products, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - Q Q Yao
- Key Laboratory of Quality and Safety Control for Milk and Dairy Products, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - Z Y Zhang
- Key Laboratory of Quality and Safety Control for Milk and Dairy Products, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - Q S Meng
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - L L Fan
- Key Laboratory of Quality and Safety Control for Milk and Dairy Products, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - J Q Wang
- Key Laboratory of Quality and Safety Control for Milk and Dairy Products, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China.
| | - N Zheng
- Key Laboratory of Quality and Safety Control for Milk and Dairy Products, Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China.
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Fan L, Wang F, Yao Q, Wu H, Wen F, Wang J, Li H, Zheng N. Lactoferrin could alleviate liver injury caused by Maillard reaction products with furan ring through regulating necroptosis pathway. Food Sci Nutr 2021; 9:3449-3459. [PMID: 34262705 PMCID: PMC8269604 DOI: 10.1002/fsn3.2254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 03/09/2021] [Accepted: 03/11/2021] [Indexed: 11/07/2022] Open
Abstract
As classical MRPs, the toxic effects of furosine, pyralline, and 5-hydroxymethylfurfural (5-HMF) in liver tissue are evaluated and the related mechanism is investigated here, and the protective effects of lactoferrin on liver injury caused by Maillard reaction products (MRPs) with furan ring are proved in vitro and in vivo. First, we detect the concentrations of furosine, pyralline, and 5-HMF in several foods using ultrahigh-performance liquid chromatography (UHPLC). Then, the effects of the three MRPs on liver cells (HL-7702) viability, as well as liver tissue, are performed and evaluated. Furthermore, the regulations of three MRPs on necroptosis-related pathway in liver cells are investigated. Additionally, the effects of lactoferrin in alleviating liver injury, as well as regulating necroptosis pathway, were evaluated. Results elucidate that lactoferrin protects liver injury caused by MRPs with furan ring structure through activating RIPK1/RIPK3/p-MLKL necroptosis pathway and downstream inflammatory reaction.
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Affiliation(s)
- Linlin Fan
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Fengen Wang
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Qianqian Yao
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Haoming Wu
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Fang Wen
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Jiaqi Wang
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Huiying Li
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
| | - Nan Zheng
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina
- State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijingChina
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A rapid UPLC method with optimized sample preparation procedures for determination of furosine in milk. J Food Compost Anal 2020. [DOI: 10.1016/j.jfca.2020.103571] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Yu H, Zhong Q, Guo Y, Xie Y, Cheng Y, Yao W. Potential of resveratrol in mitigating advanced glycation end-products formed in baked milk and baked yogurt. Food Res Int 2020; 133:109191. [DOI: 10.1016/j.foodres.2020.109191] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 02/27/2020] [Accepted: 03/17/2020] [Indexed: 02/07/2023]
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Yu H, Zhong Q, Xie Y, Guo Y, Cheng Y, Yao W. Kinetic study on the generation of furosine and pyrraline in a Maillard reaction model system of d-glucose and l-lysine. Food Chem 2020; 317:126458. [DOI: 10.1016/j.foodchem.2020.126458] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 02/03/2020] [Accepted: 02/19/2020] [Indexed: 11/30/2022]
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Li H, Yang H, Li P, Li M, Yao Q, Min L, Zhang Y, Wang J, Zheng N. Maillard reaction products with furan ring, like furosine, cause kidney injury through triggering ferroptosis pathway. Food Chem 2020; 319:126368. [PMID: 32155537 DOI: 10.1016/j.foodchem.2020.126368] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Revised: 02/03/2020] [Accepted: 02/05/2020] [Indexed: 12/21/2022]
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Yu H, Zhong Q, Liu Y, Guo Y, Xie Y, Zhou W, Yao W. Recent advances of ultrasound-assisted Maillard reaction. ULTRASONICS SONOCHEMISTRY 2020; 64:104844. [PMID: 31953006 DOI: 10.1016/j.ultsonch.2019.104844] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 09/30/2019] [Accepted: 10/25/2019] [Indexed: 06/10/2023]
Abstract
Maillard reaction (MR) is one of the most important chemical reactions in the food science domain with a long history of more than 100 years. As for ultrasound-assisted MR (US-MR), it has gradually drawn attention in a recent decade. Purpose of this paper is to provide a systematic review on recent advances of US-MR in model systems, glycation of protein, and food processing. Fundamental studies on simple MR model systems (i.e. reducing sugar and amino acid) have reported a promoted generation of colored and volatile MR products (MRPs). Critical steps influenced by US and possible mechanisms have been elucidated simultaneously. Other studies focused on modification of proteins which undergoes a glycation between proteins and saccharides as the initial stage of MR. Since the MR rate is extremely low in the presence of protein and saccharide, US becomes a promising mean of promoting the glycation. As a result, a number of functional properties of glycated protein obtained by US are significantly promoted, which extend their utilization in the food industry. The rest of studies reviewed in this article are concentrated on applying US to process real foods. Many attributes changed during US-assisted processing are induced by MR. Positive aspects brought by the promoted US-MR include enhanced antioxidant capacity and organoleptic properties (e.g. desirable color, low bitterness, enhanced flavor, etc.), as well as inhibited hazards (e.g. advanced glycation end-products, acrylamide, etc.) formed in the processed foods. Meanwhile, the promoted MR by US may also inevitably bring some negative aspects to the processed foods due to unfavored yellowish/browning colors, off-flavors and hazard components.
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Affiliation(s)
- Hang Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; Joint International Research Laboratory of Food Safety, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China.
| | - Qili Zhong
- State Key Laboratory of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; Joint International Research Laboratory of Food Safety, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China
| | - Yang Liu
- State Key Laboratory of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; Joint International Research Laboratory of Food Safety, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China
| | - Yahui Guo
- State Key Laboratory of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; Joint International Research Laboratory of Food Safety, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China
| | - Yunfei Xie
- State Key Laboratory of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; Joint International Research Laboratory of Food Safety, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China
| | - Weibiao Zhou
- Department of Food Science and Technology, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
| | - Weirong Yao
- State Key Laboratory of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China; Joint International Research Laboratory of Food Safety, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province 214122, China.
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Yao Q, Li H, Yang H, Wang J, Zheng N. Toxic Effects of Furosine by Oral Intake on Liver and Kidney and Toxicokinetics Research in Mice Acute Toxicity Model. FOOD SCIENCE AND TECHNOLOGY RESEARCH 2020; 26:495-500. [DOI: 10.3136/fstr.26.495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2025]
Affiliation(s)
- Qianqian Yao
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences
| | - Huiying Li
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences
| | - Huaigu Yang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences
| | - Jiaqi Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences
| | - Nan Zheng
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences
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Gasparre N, Betoret E, Rosell CM. Quality Indicators and Heat Damage of Dried and Cooked Gluten Free Spaghetti. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2019; 74:481-488. [PMID: 31418122 DOI: 10.1007/s11130-019-00765-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
The quality and safety indicators of commercial dried gluten free (GF) pasta were analyzed to investigate, for the first time, the real nutritional intake through the chemical composition and the heat damage during processing by quantification of furosine. Eight samples of GF spaghetti were compared with wheat spaghetti. Dried and cooked GF pasta had lower protein and ash content than wheat spaghetti. GF samples composed solely by corn flour had higher optimal cooking time. Samples with emulsifier showed lower losses during cooking. Considering their composition, no trend could be established to explain textural behavior. Samples constituted merely by corn showed the highest resilience and elasticity. Spaghetti constituted only from corn and rice showed the highest firmness. The furosine content in dried samples ranged between 19 and 134 mg FUR/100 g proteins and in cooked samples ranged between 48 to 360 mg FUR/100 g proteins. Furosine content of GF pasta was in general lower than in wheat pasta, and those differences were even enlarged when comparing them after cooking. The results of PCA indicated it was possible to discriminate GF pasta regarding their technological and nutritional behavior.
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Affiliation(s)
- N Gasparre
- Institute of Agrochemistry and Food Technology (IATA-CSIC), C/ Agustin Escardino 7, 46980, Paterna, Spain
| | - E Betoret
- Institute of Agrochemistry and Food Technology (IATA-CSIC), C/ Agustin Escardino 7, 46980, Paterna, Spain
| | - C M Rosell
- Institute of Agrochemistry and Food Technology (IATA-CSIC), C/ Agustin Escardino 7, 46980, Paterna, Spain.
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Leiva A, Molina A, Redondo-Solano M, Artavia G, Rojas-Bogantes L, Granados-Chinchilla F. Pet Food Quality Assurance and Safety and Quality Assurance Survey within the Costa Rican Pet Food Industry. Animals (Basel) 2019; 9:E980. [PMID: 31731812 PMCID: PMC6912492 DOI: 10.3390/ani9110980] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 09/23/2019] [Accepted: 09/25/2019] [Indexed: 01/22/2023] Open
Abstract
Costa Rican animal feed production is continually growing, with approximately 1,238,243 metric tons produced in 2018. Production-wise, pet cat and dog food are in fifth place (about 41,635 metric tons per year) amongst animal feeds, and it supplies up to 90% of the national market. Pet food production has increased as a response to the increase in the population of dogs and cats in Costa Rica, where 50.5% of households own at least one dog and indicates more responsible ownership in terms of feeding pets. Part of the process of making dry pet food involves a thermal process called extrusion, which is capable of eliminating the microbial load. However, extrusion can compromise nutritional quality to some extent by denaturing proteins, oxidizing lipids, and reducing digestibility. The objective of this study was to evaluate the quality and safety of dry pet food and to assess the effect of the extrusion process on digestibility and the quality of proteins, amino acids, and fatty acids. Pet food samples were collected before and after extrusion and were used to evaluate Good Manufacturing Practices (GMP), based on Central American Technical Regulation (RTCA 65.05.63:11). In general terms, weaknesses in infrastructure, documentary evidence, and post-process practices were observed in two Costa Rican feed manufactories. Feed safety was surveyed through the analysis of Salmonella spp., Escherichia coli, Listeria spp., Staphylococcus aureus, aerobic mesophilic microorganisms, fungi, and yeasts counts. The extrusion process effectively reduced pathogenic microorganisms, and showed no effect on the digestibility of dog food (p = 0.347), however, it could reduce the availability of some nutrients (e.g., amino acids, fatty acids). Furthermore, a retrospective diagnosis was made for puppy food (n = 68), dog food (n = 158), and cat food (n = 25), to evaluate the history of nutritional quality and safety. Finally, it can be confirmed that the correct implementation of GMP allows feed manufacturers to deliver a product of optimum texture, smell, nutritional composition, and safety.
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Affiliation(s)
- Astrid Leiva
- Centro de Investigación en Nutrición Animal (CINA), Universidad de Costa Rica, Ciudad Universitaria Rodrigo Facio, 11501-2060 San José, Costa Rica; (A.M.); (F.G.-C.)
| | - Andrea Molina
- Centro de Investigación en Nutrición Animal (CINA), Universidad de Costa Rica, Ciudad Universitaria Rodrigo Facio, 11501-2060 San José, Costa Rica; (A.M.); (F.G.-C.)
- Escuela de Zootecnia, Universidad de Costa Rica, Ciudad Universitaria Rodrigo Facio, 11501-2060 San José, Costa Rica
| | - Mauricio Redondo-Solano
- Centro de Investigación en Enfermedades Tropicales (CIET) and Facultad de Microbiología, Universidad de Costa Rica, Ciudad Universitaria Rodrigo, 11501-2060 San José, Costa Rica;
| | - Graciela Artavia
- Centro Nacional de Ciencia y Tecnología de Alimentos, Universidad de Costa Rica, Ciudad Universitaria Rodrigo Facio, 11501-2060 San José, Costa Rica; (G.A.); (L.R.-B.)
| | - Lizeth Rojas-Bogantes
- Centro Nacional de Ciencia y Tecnología de Alimentos, Universidad de Costa Rica, Ciudad Universitaria Rodrigo Facio, 11501-2060 San José, Costa Rica; (G.A.); (L.R.-B.)
| | - Fabio Granados-Chinchilla
- Centro de Investigación en Nutrición Animal (CINA), Universidad de Costa Rica, Ciudad Universitaria Rodrigo Facio, 11501-2060 San José, Costa Rica; (A.M.); (F.G.-C.)
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Li H, Wang B, Yang H, Wang Y, Xing L, Chen W, Wang J, Zheng N. Furosine Posed Toxic Effects on Primary Sertoli Cells through Regulating Cep55/NF-κB/PI3K/Akt/FOX01/TNF-α Pathway. Int J Mol Sci 2019; 20:ijms20153716. [PMID: 31366014 PMCID: PMC6696181 DOI: 10.3390/ijms20153716] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 07/23/2019] [Accepted: 07/25/2019] [Indexed: 12/30/2022] Open
Abstract
As one of the Maillard reaction products, furosine has been widely reported in a variety of heat-processed foods, while the toxicity of furosine on the reproductive system and related mechanisms are unclear. Here, we constructed an intragastric gavage male mice model (42-day administration, 0.1/0.25/0.5 g furosine/Kg body weight per day) to investigate its effects on mice testicle index, hormones in serum, and mice sperm quality. Besides, the lipid metabonomics analysis was performed to screen out the special metabolites and relatively altered pathways in mice testicle tissue. Mice primary sertoli cells were separated from male mice testicle to validate the role of special metabolites in regulating pathways. We found that furosine affected testicle index, hormones expression level and sperm quality, as well as caused pathological damages in testicle tissue. Phosphatidylethanolamine (PE) (18:0/16:1) was upregulated by furosine both in mice testicle tissue and in primary sertoli cells, meanwhile, PE(18:0/16:1) was proved to activate Cep55/NF-κB/PI3K/Akt/FOX01/TNF-α pathway, and as a functional protein in dairy products, lactoferrin could inhibit expression of this pathway when combined with furosine. In conclusion, for the first time we validated that furosine posed toxic effects on mice sperms and testicle tissue through upregulating PE(18:0/16:1) and activating Cep55/NF-κB/PI3K/Akt/FOX01/TNF-α pathway.
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Affiliation(s)
- Huiying Li
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Bingyuan Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Huaigu Yang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yizhen Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Lei Xing
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Wei Chen
- Shanghai Applied Protein Technology Co., Ltd., Shanghai 200030, China
| | - Jiaqi Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Nan Zheng
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
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Li H, Wang Y, Yang H, Zhang Y, Xing L, Wang J, Zheng N. Furosine, a Maillard Reaction Product, Triggers Necroptosis in Hepatocytes by Regulating the RIPK1/RIPK3/MLKL Pathway. Int J Mol Sci 2019; 20:2388. [PMID: 31091743 PMCID: PMC6566718 DOI: 10.3390/ijms20102388] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 05/11/2019] [Accepted: 05/13/2019] [Indexed: 12/22/2022] Open
Abstract
As one of the typical Maillard reaction products, furosine has been widely reported in a variety of heat-processed food. Though furosine was shown to be toxic on organs, its toxicity mechanism is still unclear. The present study aimed to investigate the toxicity mechanism of furosine in liver tissue. An intragastric gavage mice model (42-day administration, 0.1/0.25/0.5 g/kg of furosine per day) and a mice primary hepatocyte model were employed to investigate the toxicity mechanism of furosine on mice liver tissue. A metabonomics analysis of mice liver, serum, and red blood cells (RBC) was performed. The special metabolic mediator of furosine, lysophosphatidylcholine 18:0 (LPC (18:0)) was identified. Then, the effect of the upstream gene phospholipase A2 gamma (PLA2-3) on LPC (18:0), as well as the effect of furosine (100 mg/L) on the receptor-interacting serine/threonine-protein kinase (RIPK)1/RIPK3/mixed lineage kinase domain-like protein (MLKL) pathway and inflammatory factors, was determined in liver tissue and primary hepatocytes. PLA2-3 was found to regulate the level of LPC (18:0) and activate the expression of RIPK1, RIPK3, P-MLKL, and of the inflammatory factors including tumor necrosis factor α (TNF-α) and interleukin (IL-1β), both in liver tissue and in primary hepatocytes. Upon treatment with furosine, the upstream sensor PLA2-3 activated the RIPK1/RIPK3/MLKL necroptosis pathway and caused inflammation by regulating the expression of LPC (18:0), which further caused liver damage.
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Affiliation(s)
- Huiying Li
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Yizhen Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Huaigu Yang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Yangdong Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Lei Xing
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Jiaqi Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Nan Zheng
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
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18
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Gong RZ, Wang YH, Gao K, Zhang L, Liu C, Wang ZS, Wang YF, Sun YS. Quantification of Furosine (Nε-(2-Furoylmethyl)-l-lysine) in Different Parts of Velvet Antler with Various Processing Methods and Factors Affecting Its Formation. Molecules 2019; 24:molecules24071255. [PMID: 30935092 PMCID: PMC6479359 DOI: 10.3390/molecules24071255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 03/27/2019] [Accepted: 03/28/2019] [Indexed: 11/16/2022] Open
Abstract
Furosine (Nε-(2-furoylmethyl)-l-lysine) is formed during the early stages of the Maillard reaction from a lysine Amadori compound and is frequently used as a marker of reaction progress. Furosine is toxic, with significant effects on animal livers, kidneys, and other organs. However, reports on the formation of furosine in processed velvet antler are scarce. In this study, we have quantified the furosine content in processed velvet antler by using UPLC-MS/MS. The furosine contents of velvet antler after freeze-drying, boiling, and processing without and with blood were 148.51–193.93, 168.10–241.22, 60.29–80.33, and 115.18–138.99 mg/kg protein, respectively. The factors affecting furosine formation in processed velvet antler, including reducing sugars, proteins, amino acids, and process temperature, are discussed herein. Proteins, amino acids, and reducing sugars are substrates for the Maillard reaction and most significantly influence the furosine content in the processed velvet antler. High temperatures induce the production of furosine in boiled velvet antler but not in the freeze-dried samples, whereas more furosine is produced in velvet antler processed with blood, which is rich in proteins, amino acids, and reducing sugars, than in the samples processed without blood. Finally, wax slices rich in proteins, amino acids, and reducing sugars produced more furosine than the other parts of the velvet antler. These data provide a reference for guiding the production of low-furosine velvet antler and can be used to estimate the consumer intake of furosine from processed velvet antler.
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Affiliation(s)
- Rui-Ze Gong
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
| | - Yan-Hua Wang
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
- College of Chinese Material Medicine, Jilin Agricultural University, Changchun 130118, China.
| | - Kun Gao
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
- College of Chinese Material Medicine, Jilin Agricultural University, Changchun 130118, China.
| | - Lei Zhang
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
| | - Chang Liu
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
| | - Ze-Shuai Wang
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
| | - Yu-Fang Wang
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
| | - Yin-Shi Sun
- Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China.
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Li H, Xing L, Zhao N, Wang J, Zheng N. Furosine Induced Apoptosis by the Regulation of STAT1/STAT2 and UBA7/UBE2L6 Genes in HepG2 Cells. Int J Mol Sci 2018; 19:1629. [PMID: 29857509 PMCID: PMC6032202 DOI: 10.3390/ijms19061629] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 04/23/2018] [Accepted: 04/25/2018] [Indexed: 11/16/2022] Open
Abstract
As a typical product in the Miallard reaction, research on the quantitative detection of furosine is abundant, while its bioactivities and toxic effects are still unclear. Our own work recently demonstrated the induction of furosine on apoptosis in HepG2 cells, while the related mechanism remained elusive. In this study, the effects of furosine on cell viability and apoptosis were detected to select the proper dosage, and transcriptomics detection and data analysis were performed to screen out the special genes. Additionally, SiRNA fragments of the selected genes were designed and transfected into HepG2 cells to validate the role of these genes in inducing apoptosis. Results showed that furosine inhibited cell viability and induced cell apoptosis in a dose-dependent manner, as well as activated expressions of the selected genes STAT1 (signal transducer and activator of transcription 1), STAT2 (signal transducer and activator of transcription 2), UBA7 (ubiquitin-like modifier activating enzyme 7), and UBE2L6 (ubiquitin-conjugating enzyme E2L6), which significantly affected downstream apoptosis factors Caspase-3 (cysteinyl aspartate specific proteinase-3), Bcl-2 (B-cell lymphoma gene-2), Bax (BCL2-Associated gene X), and Caspase-9 (cysteinyl aspartate specific proteinase-9). For the first time, we revealed furosine induced apoptosis through two transcriptional regulators (STAT1 and STAT2) and two ubiquitination-related enzymes (UBA7 and UBE2L6).
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Affiliation(s)
- Huiying Li
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Lei Xing
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Nan Zhao
- College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.
| | - Jiaqi Wang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
| | - Nan Zheng
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
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