Hidden Enemy In Foods: Methylglyoxal

Year 2024, , 139 - 144, 30.01.2024

Melisa Akol , Dilek Taşkıran

https://doi.org/10.61399/ikcusbfd.1274527

Abstract

Methylglyoxal (MG), a toxic α-dicarbonyl compound, can be produced endogenously through various pathways. Furthermore, exogenous exposure of MG may also occur due to daily intake of several foods and beverages. Although its formation in cells is inevitable, there are some detoxification systems that prevent its accumulation in cells. The most important of the protective mechanisms against MG toxicity is the glutathione-dependent glyoxalase system, which is an antioxidant defense mechanism. In hyperglycemic conditions and high energy diet, MG may accumulate in cells due to increased production or insufficient detoxification. As a result of its excessive accumulation, MG can cross-link with DNA and cause epigenetic changes and cellular damage. It can cause mitochondrial dysfunctions and apoptosis in different cells by increasing free radical production. MG readily reacts with proteins, lipids, and nucleic acids to form advanced glycation end products (AGEs). These advanced glycation products are associated with various pathophysiological mechanisms such as diabetic complications, aging and neurodegenerative disorders. In addition to the diet, the cooking and storage methods of the foods also affect the MG content. The aim of this review is to discuss the effects of methylglyoxal on health and the ways to reduce these effects.

Keywords

Methylglyoxal, nutrients, advanced glycation end products, oxidative stress.

Project Number

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Besinlerdeki Gizli Düşman: Metilglioksal

Abstract

Toksik bir α-dikarbonil bileşiği olan metilglioksal (MG) endojen olarak çeşitli yolaklarda üretilebildiği gibi çeşitli yiyecek ve içeceklerle de vücuda alınması söz konusudur. Hücrelerde metabolik reaksiyonlar sonucu oluşumu kaçınılmazken, organizmada birikimini önleyen detoksifikasyon sistemleri mevcuttur. Bunlardan en önemlisi antioksidan bir savunma sistemi olan glutatyon bağımlı glikoksalaz enzim sistemidir. Hiperglisemik koşullarda ve yüksek enerjili beslenmede MG üretiminin artması veya detoksifikasyonun yetersiz kalması nedeniyle hücrelerde birikebilir. Aşırı birikimi sonucunda MG, DNA ile çapraz bağlar kurarak epigenetik değişikliklere ve hasarlara sebep olabilir. Hücrelerde serbest radikal üretimini arttırarak mitokondriyal disfonksiyona ve apoptoza neden olabilir. MG, ileri glikasyon son ürünlerini (AGE) oluşturmak üzere proteinler, lipidler ve nükleik asitlerle kolaylıkla reaksiyona girer. Bu ileri glikasyon ürünleri, diyabetik komplikasyonlar, yaşlanma ve nörodejeneratif bozukluklar gibi çeşitli patofizyolojik mekanizmalarla ilişkilidir. Tüketilen besinlere ek olarak, besinlerin pişirme ve depolama yöntemleri de MG içeriğini etkilemektedir. Bu derlemenin amacı, metilglioksalin sağlık üzerine etkilerini ve bu etkileri azaltma yöntemlerini tartışmaktır.

Keywords

Metilglioksal, besinler, ileri glikasyon son ürünleri, oksidatif stres

Supporting Institution

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Project Number

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Thanks

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References

• Wang Y, Ho CT. Flavour chemistry of methylglyoxal and glyoxal. Chemical Society Reviews, 2012;41(11):4140-9.
• Dhar I, Desai K. Aging: Drugs to eliminate methylglyoxal, a reactive glucose metabolite, and advanced glycation endproducts. In (Ed.), Pharmacology. IntechOpen, 2012;30:681-708.
• Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: A review. Diabetologia. 2001 Feb;44(2):129-46. doi:10.1007/ s001250051591.
• Allaman I, Bélanger M, Magistretti PJ. Methylglyoxal, the dark side of glycolysis. Front Neurosci. 2015 Feb 9;9:23. doi:10.3389/fnins.2015.00023
• Münch G, Westcott B, Menini T, Gugliucci A. Advanced glycation endproducts and their pathogenic roles in neurological disorders. Amino Acids. 2012 Apr;42(4):1221-36. doi:10.1007/s00726-010-0777-y.
• Bellahcène A, Nokin MJ, Castronovo V, Schalkwijk C. Methylglyoxal-derived stress: An emerging biological factor involved in the onset and progression of cancer. Semin Cancer Biol. 2018 Apr;49:64-74. doi:10.1016/j.semcancer.2017.05.010.
• Nigro C, Leone A, Fiory F, Prevenzano I, et al. Dicarbonyl stress at the crossroads of healthy and unhealthy aging. Cells. 2019 Jul 19;8(7):749. doi:10.3390/cells8070749.
• Degen J, Vogel M, Richter D, Hellwig M, et al. Metabolic transit of dietary methylglyoxal. J Agric Food Chem. 2013. doi: 10.1021/jf304946p.
• Yaman M. İleri glikasyon son ürünlerinin (AGEs) öncüllerinin in vitro biyoerişilebilirliklerinin bazı gıdalarda belirlenmesi. EJOSAT. 2021;(27):598-604. doi:10.31590/ejosat.990119.
• Karabudak E, Yılmaz B. Diyet kaynaklı ileri glikasyon son ürünleri ve sağlık üzerine etkileri. ACU Sağlık Bil Derg. 2018; 9(4):349-356. doi:10.31067/0.2018.55.
• Vistoli G, De Maddis D, Cipak A, Zarkovic N, et al. Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): An overview of their mechanisms of formation. Free Radic Res. 2013 Aug;47 Suppl 1:3-27. doi:10.3109/10715762.2013.815348.
• Lai SWT, Lopez Gonzalez EJ, Zoukari T, Ki P, Shuck SC. Methylglyoxal and its adducts: induction, repair, and association with disease. Chem Res Toxicol. 2022;35(10):1720-1746. doi:10.1021/acs.chemrestox.2c00160.
• Li XH, Du LL, Cheng XS, Jiang X, et al. Glycation exacerbates the neuronal toxicity of β-amyloid. Cell Death Dis. 2013 Jun 13;4(6):e673. doi:10.1038/cddis.2013.180
• Frandsen JR, Narayanasamy P. Neuroprotection through flavonoid: Enhancement of the glyoxalase pathway. Redox Biol. 2018 Apr; 14:465- 473. doi:10.1016/j.redox.2017.10.015.
• Rabbani N, Xue M, Thornalley PJ. Methylglyoxal-induced dicarbonyl stress in aging and disease: First steps towards glyoxalase 1-based treatments. Clin Sci (Lond). 2016 Oct 1;130(19):1677-96. doi:10.1042/ CS20160025.
• Tavares JF, Ribeiro PVM, Coelho OGL, Silva LE d., et al. Can advanced glycation end-products and their receptors be affected by weight loss? A systematic review. Obes Rev. 2020 Jun;21(6):e13000. doi:10.1111/ obr.13000.
• Gkogkolou P, Böhm M. Advanced glycation end products: Key players in skin aging? Dermatoendocrinol. 2012 Jul 1;4(3):259-70. doi:10.4161/derm.22028.
• Sharma C, Kaur A, Thind SS, Singh B, et al. Advanced glycation End-products (AGEs): an emerging concern for processed food industries. J Food Sci Technol. 2015 Dec;52(12):7561-76. doi:10.1007/s13197-015- 1851-y.
• Gill V, Kumar V, Singh K, Kumar A, et al. Advanced glycation end products (AGEs) may be a striking link between modern diet and health. Biomolecules. 2019 Dec 17;9(12):888. doi:10.3390/biom9120888.
• Yılmaz B, Karabudak E. Besinlerdeki ileri glikasyon son ürünleri ve azaltma yöntemleri. Beslenme ve Diyet Dergisi. 2016;44(3):280-8.
• Perrone A, Giovino A, Benny J, Martinelli F. Advanced glycation end products (AGEs): biochemistry, signaling, analytical methods, and epigenetic effects. Oxid Med Cell Longev. 2020 Mar 18;2020:3818196. doi:10.1155/2020/3818196
• Egaña-Gorroño L, López-Díez R, Yepuri G, Ramirez LS, et al. Receptor for advanced glycation end products (RAGE) and mechanisms and therapeutic opportunities in diabetes and cardiovascular disease: Insights from human subjects and animal models. Front Cardiovasc Med. 2020 Mar 10;7:37. doi:10.3389/fcvm.2020.00037.
• Ravichandran G, Lakshmanan DK, Raju K, Elangovan A, et al. Food advanced glycation end products as potential endocrine disruptors: An emerging threat to contemporary and future generation. Environ Int. 2019 Feb;123:486-500. doi:10.1016/j.envint.2018.12.032.
• Juranek J, Ray R, Banach M, Rai V. Receptor for advanced glycation end-products in neurodegenerative diseases. Rev Neurosci. 2015;26(6):691-8. doi:10.1515/revneuro-2015-0003.
• Prestes A de S, dos Santos MM, Ecker A, Zanini D, et al. Evaluation of methylglyoxal toxicity in human erythrocytes, leukocytes, and platelets. Toxicol Mech Methods. 2017 May;27(4):307-317. doi:10.1080/15376516 .2017.1285971.
• Huang X, Wang F, Chen W, Chen Y, et al. Possible link between the cognitive dysfunction associated with diabetes mellitus and the neurotoxicity of methylglyoxal. Brain Res. 2012 Aug 21;1469:82-91. doi:10.1016/j.brainres.2012.06.011.
• Nemet I, Varga-Defterdarović L, Turk Z. Methylglyoxal in food and living organisms. Mol Nutr Food Res. 2006 Dec;50(12):1105-17. doi:10.1002/mnfr.200600065.
• Pfeifer Y V, Haase PT, Kroh LW. Reactivity of thermally treated α-dicarbonyl compounds. J Agric Food Chem. 2013 Mar 27;61(12):3090- 6. doi:10.1021/jf302959k.
• Fujioka K, Shibamoto T. Formation of genotoxic dicarbonyl compounds in dietary oils upon oxidation. Lipids. 2004 May;39(5):481- 6. doi:10.1007/s11745-004-1254-y.
• Poulsen MW, Hedegaard R V., Andersen JM, de Courten B, et al. Advanced glycation endproducts in food and their effects on health. Food Chem Toxicol. 2013 Oct;60:10-37. doi:10.1016/j.fct.2013.06.052.
• Hipkiss AR. Aging risk factors and Parkinson’s disease: Contrasting roles of common dietary constituents. Neurobiol Aging. 2014 Jun;35(6):1469-72. doi:10.1016/j.neurobiolaging.2013.11.032.
• Golej Johan HH. Oral administration of methylglyoxal leads to kidney collagen accumulation in the mouse. Life Sci. 1998;63(9):801-7. doi:10.1016/s0024-3205(98)00336-1.
• Choudhary D, Chandra D, Kale RK. Influence of methylglyoxal on antioxidant enzymes and oxidative damage. Toxicol Lett. 1997 Dec;93(2- 3):141-52. doi:10.1016/s0378-4274(97)00087-8.
• Oberley LW. Free radicals and diabetes. Free Radic Biol Med. 1988;5(2):113-24. doi: 10.1016/0891-5849(88)90036-6.
• Cheng AS, Cheng YH, Lee CY, Chung CY, et al. Resveratrol protects against methylglyoxal-induced hyperglycemia and pancreatic damage in vivo. Nutrients. 2015 Apr 15;7(4):2850-65. doi:10.3390/nu7042850.
• Zhao Y, Tang Y, Sang S. Dietary quercetin reduces plasma and tissue methylglyoxal and advanced glycation end products in healthy mice treated with methylglyoxal. J Nutr. 2021 Sep 4;151(9):2601-2609. doi:10.1093/jn/nxab176.
• Kong X, Ma Ming-Zhe, Huang K, Qin L, et al. Increased plasma levels of the methylglyoxal in patients with newly diagnosed type 2 diabetes. J Diabetes. 2014 Nov;6(6):535-40. doi:10.1111/1753-0407.12160.
• Jensen TM, Vistisen D, Fleming T, Nawroth PP, et al. Methylglyoxal is associated with changes in kidney function among individuals with screen-detected Type 2 diabetes mellitus. Diabet Med. 2016 Dec;33(12):1625-1631. doi:10.1111/dme.13201.
• Vicente Miranda H, Szego ÉM, Oliveira LMA, Breda C, et al. Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies. Brain. 2017 May 1;140(5):1399-1419. doi:10.1093/ brain/awx056.
• Di Loreto S, Caracciolo V, Colafarina S, Sebastiani P, et al. Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1β and nerve growth factor in cultured hippocampal neuronal cells. Brain Res. 2004 May 1;1006(2):157-67. doi: 10.1016/j.brainres.2004.01.066.
• Chun HJ, Lee Y, Kim AH, Lee J. Methylglyoxal causes cell death in neural progenitor cells and impairs adult hippocampal neurogenesis. Neurotox Res. 2016 Apr;29(3):419-31. doi:10.1007/s12640-015-9588-y.
• Kuhla B, Lüth HJ, Haferburg D, Boeck K, et al. Methylglyoxal, glyoxal, and their detoxification in Alzheimer’s disease. Ann N Y Acad Sci. 2005 Jun;1043:211-6. doi:10.1196/annals.1333.026.
• Desai KM, Chang T, Wang H, Banigesh A, et al. Oxidative stress and aging: Is methylglyoxal the hidden enemy? Can J Physiol Pharmacol. 2010 Mar;88(3):273-84. doi:10.1139/Y10-001.
• Hipkiss AR. Dietary restriction, glycolysis, hormesis and ageing. Biogerontology. 2007 Apr;8(2):221-4. doi:10.1007/s10522-006-9034-x. doi:10.1196/annals.1433.027.
• Nagao M, Fujita Y, Sugimura T, Kosuge T. Methylglyoxal in beverages and foods: its mutagenicity and carcinogenicity. IARC Sci Publ. 1986;70:283-291.
• Tan D, Wang Y, Lo CY, Sang S, Ho CT. Methylglyoxal: its presence in beverages and potential scavengers. Ann N Y Acad Sci. 2008 Apr;1126:72-75. doi:10.1196/annals.1433.027.
• Adams CJ, Boult CH, Deadman BJ, Farr JM, Grainger MN, Manley- Harris M et al. Isolation by HPLC and characterisation of the bioactive fraction of New Zealand manuka (Leptospermum scoparium) honey. Carbohydr Res. 2008 Mar;343:651-659. doi:10.1016/j.carres.2007.12.011