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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

L-carnosine and its Derivatives as New Therapeutic Agents for the Prevention and Treatment of Vascular Complications of Diabetes

Author(s): Stefano Menini, Carla Iacobini, Claudia Blasetti Fantauzzi and Giuseppe Pugliese*

Volume 27, Issue 11, 2020

Page: [1744 - 1763] Pages: 20

DOI: 10.2174/0929867326666190711102718

Price: $65

Abstract

Vascular complications are among the most serious manifestations of diabetes. Atherosclerosis is the main cause of reduced life quality and expectancy in diabetics, whereas diabetic nephropathy and retinopathy are the most common causes of end-stage renal disease and blindness. An effective therapeutic approach to prevent vascular complications should counteract the mechanisms of injury. Among them, the toxic effects of Advanced Glycation (AGEs) and Lipoxidation (ALEs) end-products are well-recognized contributors to these sequelae. L-carnosine (β-alanyl-Lhistidine) acts as a quencher of the AGE/ALE precursors Reactive Carbonyl Species (RCS), which are highly reactive aldehydes derived from oxidative and non-oxidative modifications of sugars and lipids. Consistently, L-carnosine was found to be effective in several disease models in which glyco/lipoxidation plays a central pathogenic role. Unfortunately, in humans, L-carnosine is rapidly inactivated by serum carnosinase. Therefore, the search for carnosinase-resistant derivatives of Lcarnosine represents a suitable strategy against carbonyl stress-dependent disorders, particularly diabetic vascular complications. In this review, we present and discuss available data on the efficacy of L-carnosine and its derivatives in preventing vascular complications in rodent models of diabetes and metabolic syndrome. We also discuss genetic findings providing evidence for the involvement of the carnosinase/L-carnosine system in the risk of developing diabetic nephropathy and for preferring the use of carnosinase-resistant compounds in human disease. The availability of therapeutic strategies capable to prevent both long-term glucose toxicity, resulting from insufficient glucoselowering therapy, and lipotoxicity may help reduce the clinical and economic burden of vascular complications of diabetes and related metabolic disorders.

Keywords: Diabetes, vascular complications, atherosclerosis, diabetic nephropathy, carnosine, reactive carbonyl species, advanced glycation end-products, metabolic memory.

« Previous Next »
[1]
World Health Organization. Media Centre, Diabetes: Fact Sheet. Available at: www.who.int/mediacentre/factsheets/ fs312/en/ (Accessed: February 15,. 2018. ).
[2]
Rask-Madsen, C.; King, G.L. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab., 2013, 17(1), 20-33.
[http://dx.doi.org/10.1016/j.cmet.2012.11.012] [PMID: 23312281]
[3]
Forbes, J.M.; Fotheringham, A.K. Vascular complications in diabetes: old messages, new thoughts. Diabetologia, 2017, 60(11), 2129-2138.
[http://dx.doi.org/10.1007/s00125-017-4360-x] [PMID: 28725914]
[4]
Nathan, D.M.; Genuth, S.; Lachin, J.; Cleary, P.; Crofford, O.; Davis, M.; Rand, L.; Siebert, C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med., 1993, 329(14), 977-986.
[http://dx.doi.org/10.1056/NEJM199309303291401] [PMID: 8366922]
[5]
UK Prospective Diabetes Study (UKPDS) Group.Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet, 1998, 352(9131), 837-853.
[http://dx.doi.org/10.1016/S0140-6736(98)07019-6] [PMID: 9742976]
[6]
The DCCT Research Group.The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial. Diabetes, 1996, 45(10), 1289-1298.
[http://dx.doi.org/10.2337/diab.45.10.1289] [PMID: 8826962]
[7]
Stratton, I.M.; Adler, A.I.; Neil, H.A.; Matthews, D.R.; Manley, S.E.; Cull, C.A.; Hadden, D.; Turner, R.C.; Holman, R.R. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ, 2000, 321(7258), 405-412.
[http://dx.doi.org/10.1136/bmj.321.7258.405] [PMID: 10938048]
[8]
Patel, A.; MacMahon, S.; Chalmers, J.; Neal, B.; Billot, L.; Woodward, M.; Marre, M.; Cooper, M.; Glasziou, P.; Grobbee, D.; Hamet, P.; Harrap, S.; Heller, S.; Liu, L.; Mancia, G.; Mogensen, C.E.; Pan, C.; Poulter, N.; Rodgers, A.; Williams, B.; Bompoint, S.; de Galan, B.E.; Joshi, R.; Travert, F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med., 2008, 358(24), 2560-2572.
[http://dx.doi.org/10.1056/NEJMoa0802987] [PMID: 18539916]
[9]
Ismail-Beigi, F.; Craven, T.; Banerji, M.A.; Basile, J.; Calles, J.; Cohen, R.M.; Cuddihy, R.; Cushman, W.C.; Genuth, S.; Grimm, R.H., Jr; Hamilton, B.P.; Hoogwerf, B.; Karl, D.; Katz, L.; Krikorian, A.; O’Connor, P.; Pop-Busui, R.; Schubart, U.; Simmons, D.; Taylor, H.; Thomas, A.; Weiss, D.; Hramiak, I. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet, 2010, 376(9739), 419-430.
[http://dx.doi.org/10.1016/S0140-6736(10)60576-4] [PMID: 20594588]
[10]
Duckworth, W.; Abraira, C.; Moritz, T.; Reda, D.; Emanuele, N.; Reaven, P.D.; Zieve, F.J.; Marks, J.; Davis, S.N.; Hayward, R.; Warren, S.R.; Goldman, S.; McCarren, M.; Vitek, M.E.; Henderson, W.G.; Huang, G.D. Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med., 2009, 360(2), 129-139.
[http://dx.doi.org/10.1056/NEJMoa0808431] [PMID: 19092145]
[11]
Gerstein, H.C.; Miller, M.E.; Byington, R.P.; Goff, D.C., Jr; Bigger, J.T.; Buse, J.B.; Cushman, W.C.; Genuth, S.; Ismail-Beigi, F.; Grimm, R.H., Jr; Probstfield, J.L.; Simons-Morton, D.G.; Friedewald, W.T. Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med., 2008, 358(24), 2545-2559.
[http://dx.doi.org/10.1056/NEJMoa0802743] [PMID: 18539917]
[12]
Seaquist, E.R.; Miller, M.E.; Bonds, D.E.; Feinglos, M.; Goff, D.C., Jr; Peterson, K.; Senior, P. The impact of frequent and unrecognized hypoglycemia on mortality in the ACCORD study. Diabetes Care, 2012, 35(2), 409-414.
[http://dx.doi.org/10.2337/dc11-0996] [PMID: 22179956]
[13]
Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA, 2002, 287(19), 2563-2569.
[http://dx.doi.org/10.1001/jama.287.19.2563] [PMID: 12020338]
[14]
Nathan, D.M.; Cleary, P.A.; Backlund, J.Y.; Genuth, S.M.; Lachin, J.M.; Orchard, T.J.; Raskin, P.; Zinman, B. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med., 2005, 353(25), 2643-2653.
[http://dx.doi.org/10.1056/NEJMoa052187] [PMID: 16371630]
[15]
Holman, R.R.; Paul, S.K.; Bethel, M.A.; Matthews, D.R.; Neil, H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med., 2008, 359(15), 1577-1589.
[http://dx.doi.org/10.1056/NEJMoa0806470] [PMID: 18784090]
[16]
Hayward, R.A.; Reaven, P.D.; Wiitala, W.L.; Bahn, G.D.; Reda, D.J.; Ge, L.; McCarren, M.; Duckworth, W.C.; Emanuele, N.V. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med., 2015, 372(23), 2197-2206.
[http://dx.doi.org/10.1056/NEJMoa1414266] [PMID: 26039600]
[17]
Zoungas, S.; Chalmers, J.; Neal, B.; Billot, L.; Li, Q.; Hirakawa, Y.; Arima, H.; Monaghan, H.; Joshi, R.; Colagiuri, S.; Cooper, M.E.; Glasziou, P.; Grobbee, D.; Hamet, P.; Harrap, S.; Heller, S.; Lisheng, L.; Mancia, G.; Marre, M.; Matthews, D.R.; Mogensen, C.E.; Perkovic, V.; Poulter, N.; Rodgers, A.; Williams, B.; MacMahon, S.; Patel, A.; Woodward, M. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N. Engl. J. Med., 2014, 371(15), 1392-1406.
[http://dx.doi.org/10.1056/NEJMoa1407963] [PMID: 25234206]
[18]
ACCORD Study Group.Nine-year effects of 3.7 years of intensive glycemic control on cardiovascular outcomes diabetes care. Diabetes Care, 2016, 39(5), 701-708.
[http://dx.doi.org/10.2337/dc15-2283] [PMID: 26822326]
[19]
Chilelli, N.C.; Burlina, S.; Lapolla, A. AGEs, rather than hyperglycemia, are responsible for microvascular complications in diabetes: a “glycoxidation-centric” point of view. Nutr. Metab. Cardiovasc. Dis., 2013, 23(10), 913-919.
[http://dx.doi.org/10.1016/j.numecd.2013.04.004] [PMID: 23786818]
[20]
Menini, S.; Iacobini, C.; Ricci, C.; Blasetti Fantauzzi, C.; Pugliese, G. Protection from diabetes-induced atherosclerosis and renal disease by D-carnosine-octylester: effects of early vs late inhibition of advanced glycation end-products in Apoe-null mice. Diabetologia, 2015, 58(4), 845-853.
[http://dx.doi.org/10.1007/s00125-014-3467-6] [PMID: 25471794]
[21]
Gerrits, E.G.; Lutgers, H.L.; Kleefstra, N.; Graaff, R.; Groenier, K.H.; Smit, A.J.; Gans, R.O.; Bilo, H.J. Skin autofluorescence: a tool to identify type 2 diabetic patients at risk for developing microvascular complications. Diabetes Care, 2008, 31(3), 517-521.
[http://dx.doi.org/10.2337/dc07-1755] [PMID: 18039805]
[22]
Maillard, L.C. Action of amino acids on sugars: formation of melanoidins in a methodical way. Compt. Rend., 1912, 154, 66.
[23]
Koenig, R.J.; Peterson, C.M.; Jones, R.L.; Saudek, C.; Lehrman, M.; Cerami, A. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. N. Engl. J. Med., 1976, 295(8), 417-420.
[http://dx.doi.org/10.1056/NEJM197608192950804] [PMID: 934240]
[24]
Brownlee, M.; Vlassara, H.; Kooney, A.; Ulrich, P.; Cerami, A. Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science, 1986, 232(4758), 1629-1632.
[http://dx.doi.org/10.1126/science.3487117] [PMID: 3487117]
[25]
Ahmed, M.U.; Thorpe, S.R.; Baynes, J.W. Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J. Biol. Chem., 1986, 261(11), 4889-4894.
[PMID: 3082871]
[26]
Ahmed, N. Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res. Clin. Pract., 2005, 67(1), 3-21.
[http://dx.doi.org/10.1016/j.diabres.2004.09.004] [PMID: 15620429]
[27]
Baynes, J.W.; Thorpe, S.R. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes, 1999, 48(1), 1-9.
[http://dx.doi.org/10.2337/diabetes.48.1.1] [PMID: 9892215]
[28]
Koschinsky, T.; He, C.J.; Mitsuhashi, T.; Bucala, R.; Liu, C.; Buenting, C.; Heitmann, K.; Vlassara, H. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc. Natl. Acad. Sci. USA, 1997, 94(12), 6474-6479.
[http://dx.doi.org/10.1073/pnas.94.12.6474] [PMID: 9177242]
[29]
Cerami, C.; Founds, H.; Nicholl, I.; Mitsuhashi, T.; Giordano, D.; Vanpatten, S.; Lee, A.; Al-Abed, Y.; Vlassara, H.; Bucala, R.; Cerami, A. Tobacco smoke is a source of toxic reactive glycation products. Proc. Natl. Acad. Sci. USA, 1997, 94(25), 13915-13920.
[http://dx.doi.org/10.1073/pnas.94.25.13915] [PMID: 9391127]
[30]
Reddy, S.; Bichler, J.; Wells-Knecht, K.J.; Thorpe, S.R.; Baynes, J.W. N epsilon-(carboxymethyl)lysine is a dominant advanced glycation end product (AGE) antigen in tissue proteins. Biochemistry, 1995, 34(34), 10872-10878.
[http://dx.doi.org/10.1021/bi00034a021] [PMID: 7662668]
[31]
Fu, M.X.; Requena, J.R.; Jenkins, A.J.; Lyons, T.J.; Baynes, J.W.; Thorpe, S.R. The advanced glycation end product, Nepsilon-(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J. Biol. Chem., 1996, 271(17), 9982-9986.
[http://dx.doi.org/10.1074/jbc.271.17.9982] [PMID: 8626637]
[32]
Pugliese, G.; Iacobini, C.; Pesce, C.M.; Menini, S. Galectin-3: an emerging all-out player in metabolic disorders and their complications. Glycobiology, 2015, 25(2), 136-150.
[http://dx.doi.org/10.1093/glycob/cwu111] [PMID: 25303959]
[33]
Bohlender, J.M.; Franke, S.; Stein, G.; Wolf, G. Advanced glycation end products and the kidney. Am. J. Physiol. Renal Physiol., 2005, 289(4), F645-F659.
[http://dx.doi.org/10.1152/ajprenal.00398.2004] [PMID: 16159899]
[34]
Uchida, K. Role of reactive aldehyde in cardiovascular diseases. Free Radic. Biol. Med., 2000, 28(12), 1685-1696.
[http://dx.doi.org/10.1016/S0891-5849(00)00226-4] [PMID: 10946210]
[35]
Goh, S.Y.; Cooper, M.E. Clinical review: The role of advanced glycation end products in progression and complications of diabetes. J. Clin. Endocrinol. Metab., 2008, 93(4), 1143-1152.
[http://dx.doi.org/10.1210/jc.2007-1817] [PMID: 18182449]
[36]
Heeringa, P.; Tervaert, J.W. Role of oxidized low-density lipoprotein in renal disease. Curr. Opin. Nephrol. Hypertens., 2002, 11(3), 287-293.
[http://dx.doi.org/10.1097/00041552-200205000-00004] [PMID: 11981258]
[37]
Lusis, A.J. Atherosclerosis. Nature, 2000, 407(6801), 233-241.
[http://dx.doi.org/10.1038/35025203] [PMID: 11001066]
[38]
Yang, C.W.; Vlassara, H.; Peten, E.P.; He, C.J.; Striker, G.E.; Striker, L.J. Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease. Proc. Natl. Acad. Sci. USA, 1994, 91(20), 9436-9440.
[http://dx.doi.org/10.1073/pnas.91.20.9436] [PMID: 7937785]
[39]
Vlassara, H.; Fuh, H.; Makita, Z.; Krungkrai, S.; Cerami, A.; Bucala, R. Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc. Natl. Acad. Sci. USA, 1992, 89(24), 12043-12047.
[http://dx.doi.org/10.1073/pnas.89.24.12043] [PMID: 1465438]
[40]
Vlassara, H.; Fuh, H.; Donnelly, T.; Cybulsky, M. Advanced glycation endproducts promote adhesion molecule (VCAM-1, ICAM-1) expression and atheroma formation in normal rabbits. Mol. Med., 1995, 1(4), 447-456.
[http://dx.doi.org/10.1007/BF03401582] [PMID: 8521302]
[41]
Iacobini, C.; Menini, S.; Oddi, G.; Ricci, C.; Amadio, L.; Pricci, F.; Olivieri, A.; Sorcini, M.; Di Mario, U.; Pesce, C.; Pugliese, G. Galectin-3/AGE-receptor 3 knockout mice show accelerated AGE-induced glomerular injury: evidence for a protective role of galectin-3 as an AGE receptor. FASEB J., 2004, 18(14), 1773-1775.
[http://dx.doi.org/10.1096/fj.04-2031fje] [PMID: 15361471]
[42]
Menini, S.; Iacobini, C.; Ricci, C.; Oddi, G.; Pesce, C.; Pugliese, F.; Block, K.; Abboud, H.E.; Giorgio, M.; Migliaccio, E.; Pelicci, P.G.; Pugliese, G. Ablation of the gene encoding p66Shc protects mice against AGE-induced glomerulopathy by preventing oxidant-dependent tissue injury and further AGE accumulation. Diabetologia, 2007, 50(9), 1997-2007.
[http://dx.doi.org/10.1007/s00125-007-0728-7] [PMID: 17611735]
[43]
Hanssen, N.M.; Wouters, K.; Huijberts, M.S.; Gijbels, M.J.; Sluimer, J.C.; Scheijen, J.L.; Heeneman, S.; Biessen, E.A.; Daemen, M.J.; Brownlee, M.; de Kleijn, D.P.; Stehouwer, C.D.; Pasterkamp, G.; Schalkwijk, C.G. Higher levels of advanced glycation endproducts in human carotid atherosclerotic plaques are associated with a rupture-prone phenotype. Eur. Heart J., 2014, 35(17), 1137-1146.
[http://dx.doi.org/10.1093/eurheartj/eht402] [PMID: 24126878]
[44]
Aso, Y.; Inukai, T.; Tayama, K.; Takemura, Y. Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes. Acta Diabetol., 2000, 37(2), 87-92.
[http://dx.doi.org/10.1007/s005920070025] [PMID: 11194933]
[45]
Kilhovd, B.K.; Juutilainen, A.; Lehto, S.; Rönnemaa, T.; Torjesen, P.A.; Hanssen, K.F.; Laakso, M. Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study. Diabetologia, 2007, 50(7), 1409-1417.
[http://dx.doi.org/10.1007/s00125-007-0687-z] [PMID: 17479244]
[46]
Nakamura, Y.; Horii, Y.; Nishino, T.; Shiiki, H.; Sakaguchi, Y.; Kagoshima, T.; Dohi, K.; Makita, Z.; Vlassara, H.; Bucala, R. Immunohistochemical localization of advanced glycosylation end products in coronary atheroma and cardiac tissue in diabetes mellitus. Am. J. Pathol., 1993, 143(6), 1649-1656.
[PMID: 8256853]
[47]
Schleicher, E.; Weigert, C.; Rohrbach, H.; Nerlich, A.; Bachmeier, B.; Friess, U. Role of glucoxidation and lipid oxidation in the development of atherosclerosis. Ann. N. Y. Acad. Sci., 2005, 1043, 343-354.
[http://dx.doi.org/10.1196/annals.1333.041] [PMID: 16037256]
[48]
Forbes, J.M.; Cooper, M.E.; Oldfield, M.D.; Thomas, M.C. Role of advanced glycation end products in diabetic nephropathy. J. Am. Soc. Nephrol., 2003, 14(8)(Suppl. 3), S254-S258.
[http://dx.doi.org/10.1097/01.ASN.0000077413.41276.17] [PMID: 12874442]
[49]
Bakris, G.L.; Bank, A.J.; Kass, D.A.; Neutel, J.M.; Preston, R.A.; Oparil, S. Advanced glycation end-product cross-link breakers. A novel approach to cardiovascular pathologies related to the aging process. Am. J. Hypertens., 2004, 17(12 Pt 2), 23S-30S.
[http://dx.doi.org/10.1016/j.amjhyper.2004.08.022] [PMID: 15607432]
[50]
Reddy, V.P.; Beyaz, A. Inhibitors of the Maillard reaction and AGE breakers as therapeutics for multiple diseases. Drug Discov. Today, 2006, 11(13-14), 646-654.
[http://dx.doi.org/10.1016/j.drudis.2006.05.016] [PMID: 16793534]
[51]
Negre-Salvayre, A.; Coatrieux, C.; Ingueneau, C.; Salvayre, R. Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. Br. J. Pharmacol., 2008, 153(1), 6-20.
[http://dx.doi.org/10.1038/sj.bjp.0707395] [PMID: 17643134]
[52]
Ellis, E.M. Reactive carbonyls and oxidative stress: potential for therapeutic intervention. Pharmacol. Ther., 2007, 115(1), 13-24.
[http://dx.doi.org/10.1016/j.pharmthera.2007.03.015] [PMID: 17570531]
[53]
Aldini, G.; Facino, R.M.; Beretta, G.; Carini, M. Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives. Biofactors, 2005, 24(1-4), 77-87.
[http://dx.doi.org/10.1002/biof.5520240109] [PMID: 16403966]
[54]
Peters, V.; Zschocke, J.; Schmitt, C.P. Carnosinase, diabetes mellitus and the potential relevance of carnosinase deficiency. J. Inherit. Metab. Dis., 2018, 41(1), 39-47.
[http://dx.doi.org/10.1007/s10545-017-0099-2] [PMID: 29027595]
[55]
Drozak, J.; Veiga-da-Cunha, M.; Vertommen, D.; Stroobant, V.; Van Schaftingen, E. Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J. Biol. Chem., 2010, 285(13), 9346-9356.
[http://dx.doi.org/10.1074/jbc.M109.095505] [PMID: 20097752]
[56]
Peters, V.; Klessens, C.Q.; Baelde, H.J.; Singler, B.; Veraar, K.A.; Zutinic, A.; Drozak, J.; Zschocke, J.; Schmitt, C.P.; de Heer, E. Intrinsic carnosine metabolism in the human kidney. Amino Acids, 2015, 47(12), 2541-2550.
[http://dx.doi.org/10.1007/s00726-015-2045-7] [PMID: 26206726]
[57]
Guiotto, A.; Ruzza, P.; Babizhayev, M.A.; Calderan, A. Malondialdehyde scavenging and aldose-derived Schiff bases’ transglycation properties of synthetic histidyl-hydrazide carnosine analogs. Bioorg. Med. Chem., 2007, 15(18), 6158-6163.
[http://dx.doi.org/10.1016/j.bmc.2007.06.029] [PMID: 17604632]
[58]
Rashid, I.; van Reyk, D.M.; Davies, M.J. Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett., 2007, 581(5), 1067-1070.
[http://dx.doi.org/10.1016/j.febslet.2007.01.082] [PMID: 17316626]
[59]
Nokin, M.J.; Durieux, F.; Peixoto, P.; Chiavarina, B.; Peulen, O.; Blomme, A.; Turtoi, A.; Costanza, B.; Smargiasso, N.; Baiwir, D.; Scheijen, J.L.; Schalkwijk, C.G.; Leenders, J.; De Tullio, P.; Bianchi, E.; Thiry, M.; Uchida, K.; Spiegel, D.A.; Cochrane, J.R.; Hutton, C.A.; De Pauw, E.; Delvenne, P.; Belpomme, D.; Castronovo, V.; Bellahcène, A. Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis. eLife,, 2016. 5, e19375
[http://dx.doi.org/10.7554/eLife.19375] [PMID: 27759563]
[60]
Weigand, T.; Singler, B.; Fleming, T.; Nawroth, P.; Klika, K.D.; Thiel, C.; Baelde, H.; Garbade, S.F.; Wagner, A.H.; Hecker, M.; Yard, B.A.; Amberger, A.; Zschocke, J.; Schmitt, C.P.; Peters, V. Carnosine catalyzes the formation of the oligo/polymeric products of methylglyoxal. Cell. Physiol. Biochem., 2018, 46(2), 713-726.
[http://dx.doi.org/10.1159/000488727] [PMID: 29621776]
[61]
Mozdzan, M.; Szemraj, J.; Rysz, J.; Nowak, D. Antioxidant properties of carnosine re-evaluated with oxidizing systems involving iron and copper ions. Basic Clin. Pharmacol. Toxicol., 2005, 96(5), 352-360.
[http://dx.doi.org/10.1111/j.1742-7843.2005.pto_03.x] [PMID: 15853927]
[62]
Decker, E.A.; Livisay, S.A.; Zhou, S. A re-evaluation of the antioxidant activity of purified carnosine. Biochemistry (Mosc.), 2000, 65(7), 766-770.
[PMID: 10951093]
[63]
Velez, S.; Nair, N.G.; Reddy, V.P. Transition metal ion binding studies of carnosine and histidine: biologically relevant antioxidants. Colloids Surf. B Biointerfaces, 2008, 66(2), 291-294.
[http://dx.doi.org/10.1016/j.colsurfb.2008.06.012] [PMID: 18675540]
[64]
Menini, S.; Iacobini, C.; Ricci, C.; Scipioni, A.; Blasetti Fantauzzi, C.; Giaccari, A.; Salomone, E.; Canevotti, R.; Lapolla, A.; Orioli, M.; Aldini, G.; Pugliese, G. D-Carnosine octylester attenuates atherosclerosis and renal disease in ApoE null mice fed a Western diet through reduction of carbonyl stress and inflammation. Br. J. Pharmacol., 2012, 166(4), 1344-1356.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01834.x] [PMID: 22229552]
[65]
Iacobini, C.; Menini, S.; Blasetti Fantauzzi, C.; Pesce, C.M.; Giaccari, A.; Salomone, E.; Lapolla, A.; Orioli, M.; Aldini, G.; Pugliese, G. FL-926-16, a novel bioavailable carnosinase-resistant carnosine derivative, prevents onset and stops progression of diabetic nephropathy in db/db mice. Br. J. Pharmacol., 2018, 175(1), 53-66.
[http://dx.doi.org/10.1111/bph.14070] [PMID: 29053168]
[66]
Pattison, D.I.; Davies, M.J. Evidence for rapid inter- and intramolecular chlorine transfer reactions of histamine and carnosine chloramines: implications for the prevention of hypochlorous-acid-mediated damage. Biochemistry, 2006, 45(26), 8152-8162.
[http://dx.doi.org/10.1021/bi060348s] [PMID: 16800640]
[67]
Boldyrev, A.A.; Aldini, G.; Derave, W. Physiology and pathophysiology of carnosine. Physiol. Rev., 2013, 93(4), 1803-1845.
[http://dx.doi.org/10.1152/physrev.00039.2012] [PMID: 24137022]
[68]
Boldyrev, A.; Bulygina, E.; Leinsoo, T.; Petrushanko, I.; Tsubone, S.; Abe, H. Protection of neuronal cells against reactive oxygen species by carnosine and related compounds. Comp. Biochem. Physiol. B Biochem. Mol. Biol., 2004, 137(1), 81-88.
[http://dx.doi.org/10.1016/j.cbpc.2003.10.008] [PMID: 14698913]
[69]
Hobart, L.J.; Seibel, I.; Yeargans, G.S.; Seidler, N.W. Anti-crosslinking properties of carnosine: significance of histidine. Life Sci., 2004, 75(11), 1379-1389.
[http://dx.doi.org/10.1016/j.lfs.2004.05.002] [PMID: 15234195]
[70]
Wada, N.; Yamanaka, S.; Shibato, J.; Rakwal, R.; Hirako, S.; Iizuka, Y.; Kim, H.; Matsumoto, A.; Kimura, A.; Takenoya, F.; Yasunaga, G.; Shioda, S. Behavioral and omics analyses study on potential involvement of dipeptide balenine through supplementation in diet of senescence-accelerated mouse prone 8. Genom. Data, 2016, 10, 38-50.
[http://dx.doi.org/10.1016/j.gdata.2016.09.004] [PMID: 27672559]
[71]
Orioli, M.; Aldini, G.; Benfatto, M.C.; Facino, R.M.; Carini, M. HNE Michael adducts to histidine and histidine-containing peptides as biomarkers of lipid-derived carbonyl stress in urines: LC-MS/MS profiling in Zucker obese rats. Anal. Chem., 2007, 79(23), 9174-9184.
[http://dx.doi.org/10.1021/ac7016184] [PMID: 17979257]
[72]
Aldini, G.; Dalle-Donne, I.; Colombo, R.; Maffei Facino, R.; Milzani, A.; Carini, M. Lipoxidation-derived reactive carbonyl species as potential drug targets in preventing protein carbonylation and related cellular dysfunction. ChemMedChem, 2006, 1(10), 1045-1058.
[http://dx.doi.org/10.1002/cmdc.200600075] [PMID: 16915603]
[73]
Boldyrev, A.A. Protection of proteins from oxidative stress: a new illusion or a novel strategy? Ann. N. Y. Acad. Sci., 2005, 1057(1), 193-205.
[http://dx.doi.org/10.1196/annals.1356.013] [PMID: 16399895]
[74]
Hipkiss, A.R.; Baye, E.; de Courten, B. Carnosine and the processes of ageing. Maturitas, 2016, 93, 28-33.
[http://dx.doi.org/10.1016/j.maturitas.2016.06.002] [PMID: 27344459]
[75]
Babizhayev, M.A. Biological activities of the natural imidazole-containing peptidomimetics n-acetylcarnosine, carcinine and L-carnosine in ophthalmic and skin care products. Life Sci., 2006, 78(20), 2343-2357.
[http://dx.doi.org/10.1016/j.lfs.2005.09.054] [PMID: 16388826]
[76]
Kurata, H.; Fujii, T.; Tsutsui, H.; Katayama, T.; Ohkita, M.; Takaoka, M.; Tsuruoka, N.; Kiso, Y.; Ohno, Y.; Fujisawa, Y.; Shokoji, T.; Nishiyama, A.; Abe, Y.; Matsumura, Y. Renoprotective effects of l-carnosine on ischemia/reperfusion-induced renal injury in rats. J. Pharmacol. Exp. Ther., 2006, 319(2), 640-647.
[http://dx.doi.org/10.1124/jpet.106.110122] [PMID: 16916994]
[77]
Soliman, K.M.; Abdul-Hamid, M.; Othman, A.I. Effect of carnosine on gentamicin-induced nephrotoxicity. Med. Sci. Monit., 2007, 13(3), BR73-BR83.
[PMID: 17325631]
[78]
Cuzzocrea, S.; Genovese, T.; Failla, M.; Vecchio, G.; Fruciano, M.; Mazzon, E.; Di Paola, R.; Muià, C.; La Rosa, C.; Crimi, N.; Rizzarelli, E.; Vancheri, C. Protective effect of orally administered carnosine on bleomycin-induced lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol., 2007, 292(5), L1095-L1104.
[http://dx.doi.org/10.1152/ajplung.00283.2006] [PMID: 17220373]
[79]
Rajanikant, G.K.; Zemke, D.; Senut, M.C.; Frenkel, M.B.; Chen, A.F.; Gupta, R.; Majid, A. Carnosine is neuroprotective against permanent focal cerebral ischemia in mice. Stroke, 2007, 38(11), 3023-3031.
[http://dx.doi.org/10.1161/STROKEAHA.107.488502] [PMID: 17916766]
[80]
Tang, S.C.; Arumugam, T.V.; Cutler, R.G.; Jo, D.G.; Magnus, T.; Chan, S.L.; Mughal, M.R.; Telljohann, R.S.; Nassar, M.; Ouyang, X.; Calderan, A.; Ruzza, P.; Guiotto, A.; Mattson, M.P. Neuroprotective actions of a histidine analogue in models of ischemic stroke. J. Neurochem., 2007, 101(3), 729-736.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04412.x] [PMID: 17254011]
[81]
Janssen, B.; Hohenadel, D.; Brinkkoetter, P.; Peters, V.; Rind, N.; Fischer, C.; Rychlik, I.; Cerna, M.; Romzova, M.; de Heer, E.; Baelde, H.; Bakker, S.J.; Zirie, M.; Rondeau, E.; Mathieson, P.; Saleem, M.A.; Meyer, J.; Köppel, H.; Sauerhoefer, S.; Bartram, C.R.; Nawroth, P.; Hammes, H.P.; Yard, B.A.; Zschocke, J.; van der Woude, F.J. Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1. Diabetes, 2005, 54(8), 2320-2327.
[http://dx.doi.org/10.2337/diabetes.54.8.2320] [PMID: 16046297]
[82]
Alhamdani, M.S.; Al-Kassir, A.H.; Abbas, F.K.; Jaleel, N.A.; Al-Taee, M.F. Antiglycation and antioxidant effect of carnosine against glucose degradation products in peritoneal mesothelial cells. Nephron Clin. Pract., 2007, 107(1), c26-c34.
[http://dx.doi.org/10.1159/000106509] [PMID: 17664891]
[83]
Shen, Y.; Hu, W.W.; Fan, Y.Y.; Dai, H.B.; Fu, Q.L.; Wei, E.Q.; Luo, J.H.; Chen, Z. Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H(1)/H(3) receptors. Biochem. Pharmacol., 2007, 73(5), 709-717.
[http://dx.doi.org/10.1016/j.bcp.2006.11.007] [PMID: 17169331]
[84]
Calabrese, V.; Colombrita, C.; Guagliano, E.; Sapienza, M.; Ravagna, A.; Cardile, V.; Scapagnini, G.; Santoro, A.M.; Mangiameli, A.; Butterfield, D.A.; Giuffrida Stella, A.M.; Rizzarelli, E. Protective effect of carnosine during nitrosative stress in astroglial cell cultures. Neurochem. Res., 2005, 30(6-7), 797-807.
[http://dx.doi.org/10.1007/s11064-005-6874-8] [PMID: 16187215]
[85]
Jia, H.; Qi, X.; Fang, S.; Jin, Y.; Han, X.; Wang, Y.; Wang, A.; Zhou, H. Carnosine inhibits high glucose-induced mesangial cell proliferation through mediating cell cycle progression. Regul. Pept., 2009, 154(1-3), 69-76.
[http://dx.doi.org/10.1016/j.regpep.2008.12.004] [PMID: 19154760]
[86]
Köppel, H.; Riedl, E.; Braunagel, M.; Sauerhoefer, S.; Ehnert, S.; Godoy, P.; Sternik, P.; Dooley, S.; Yard, B.A. L-carnosine inhibits high-glucose-mediated matrix accumulation in human mesangial cells by interfering with TGF-β production and signalling. Nephrol. Dial. Transplant., 2011, 26(12), 3852-3858.
[http://dx.doi.org/10.1093/ndt/gfr324] [PMID: 21750159]
[87]
Albrecht, T.; Schilperoort, M.; Zhang, S.; Braun, J.D.; Qiu, J.; Rodriguez, A.; Pastene, D.O.; Krämer, B.K.; Köppel, H.; Baelde, H.; de Heer, E.; Anna Altomare, A.; Regazzoni, L.; Denisi, A.; Aldini, G.; van den Born, J.; Yard, B.A.; Hauske, S.J. Carnosine attenuates the development of both type 2 diabetes and diabetic nephropathy in BTBR ob/ob mice. Sci. Rep., 2017, 7, 44492.
[http://dx.doi.org/10.1038/srep44492] [PMID: 28281693]
[88]
Hudkins, K.L.; Pichaiwong, W.; Wietecha, T.; Kowalewska, J.; Banas, M.C.; Spencer, M.W.; Mühlfeld, A.; Koelling, M.; Pippin, J.W.; Shankland, S.J.; Askari, B.; Rabaglia, M.E.; Keller, M.P.; Attie, A.D.; Alpers, C.E. BTBR Ob/Ob mutant mice model progressive diabetic nephropathy. J. Am. Soc. Nephrol., 2010, 21(9), 1533-1542.
[http://dx.doi.org/10.1681/ASN.2009121290] [PMID: 20634301]
[89]
Aldini, G.; Orioli, M.; Rossoni, G.; Savi, F.; Braidotti, P.; Vistoli, G.; Yeum, K.J.; Negrisoli, G.; Carini, M. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats. J. Cell. Mol. Med., 2011, 15(6), 1339-1354.
[http://dx.doi.org/10.1111/j.1582-4934.2010.01101.x] [PMID: 20518851]
[90]
Hansen, B.C. The metabolic syndrome X. Ann. N. Y. Acad. Sci., 1999, 892, 1-24.
[http://dx.doi.org/10.1111/j.1749-6632.1999.tb07782.x] [PMID: 10842649]
[91]
Peters, V.; Schmitt, C.P.; Zschocke, J.; Gross, M.L.; Brismar, K.; Forsberg, E. Carnosine treatment largely prevents alterations of renal carnosine metabolism in diabetic mice. Amino Acids, 2012, 42(6), 2411-2416.
[http://dx.doi.org/10.1007/s00726-011-1046-4] [PMID: 21833769]
[92]
Sharma, K.; McCue, P.; Dunn, S.R. Diabetic kidney disease in the db/db mouse. Am. J. Physiol. Renal Physiol., 2003, 284(6), F1138-F1144.
[http://dx.doi.org/10.1152/ajprenal.00315.2002] [PMID: 12736165]
[93]
Hammes, H.P.; Lin, J.; Renner, O.; Shani, M.; Lundqvist, A.; Betsholtz, C.; Brownlee, M.; Deutsch, U. Pericytes and the pathogenesis of diabetic retinopathy. Diabetes, 2002, 51(10), 3107-3112.
[http://dx.doi.org/10.2337/diabetes.51.10.3107] [PMID: 12351455]
[94]
Lai, A.K.; Lo, A.C. Animal models of diabetic retinopathy: summary and comparison. J. Diabetes Res., 2013, 2013 106594
[http://dx.doi.org/10.1155/2013/106594] [PMID: 24286086]
[95]
Pfister, F.; Riedl, E.; Wang, Q.; vom Hagen, F.; Deinzer, M.; Harmsen, M.C.; Molema, G.; Yard, B.; Feng, Y.; Hammes, H.P. Oral carnosine supplementation prevents vascular damage in experimental diabetic retinopathy. Cell. Physiol. Biochem., 2011, 28(1), 125-136.
[http://dx.doi.org/10.1159/000331721] [PMID: 21865855]
[96]
Gul, A.; Rahman, M.A.; Salim, A.; Simjee, S.U. Advanced glycation end products in senile diabetic and nondiabetic patients with cataract. J. Diabetes Complications, 2009, 23(5), 343-348.
[http://dx.doi.org/10.1016/j.jdiacomp.2008.04.001] [PMID: 18508288]
[97]
Stirban, A. Microvascular dysfunction in the context of diabetic neuropathy. Curr. Diab. Rep., 2014, 14(11), 541.
[http://dx.doi.org/10.1007/s11892-014-0541-x] [PMID: 25189434]
[98]
Lupachyk, S.; Shevalye, H.; Maksimchyk, Y.; Drel, V.R.; Obrosova, I.G. PARP inhibition alleviates diabetes-induced systemic oxidative stress and neural tissue 4-hydroxynonenal adduct accumulation: correlation with peripheral nerve function. Free Radic. Biol. Med., 2011, 50(10), 1400-1409.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.01.037] [PMID: 21300148]
[99]
Negre-Salvayre, A.; Auge, N.; Ayala, V.; Basaga, H.; Boada, J.; Brenke, R.; Chapple, S.; Cohen, G.; Feher, J.; Grune, T.; Lengyel, G.; Mann, G.E.; Pamplona, R.; Poli, G.; Portero-Otin, M.; Riahi, Y.; Salvayre, R.; Sasson, S.; Serrano, J.; Shamni, O.; Siems, W.; Siow, R.C.M.; Wiswedel, I.; Zarkovic, K.; Zarkovic, N. Pathological aspects of lipid peroxidation. Free Radic. Res., 2010, 44(10), 1125-1171.
[http://dx.doi.org/10.3109/10715762.2010.498478] [PMID: 20836660]
[100]
Kamei, J.; Ohsawa, M.; Miyata, S.; Tanaka, S. Preventive effect of L-carnosine on changes in the thermal nociceptive threshold in streptozotocin-induced diabetic mice. Eur. J. Pharmacol., 2008, 600(1-3), 83-86.
[http://dx.doi.org/10.1016/j.ejphar.2008.10.002] [PMID: 18930724]
[101]
Domingueti, C.P.; Dusse, L.M.; Carvalho, Md.; de Sousa, L.P.; Gomes, K.B.; Fernandes, A.P. Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J. Diabetes Complications, 2016, 30(4), 738-745.
[http://dx.doi.org/10.1016/j.jdiacomp.2015.12.018] [PMID: 26781070]
[102]
Boyle, P.J. Diabetes mellitus and macrovascular disease: mechanisms and mediators. Am. J. Med., 2007, 120(1), S12-S17.
[http://dx.doi.org/10.1016/j.amjmed.2007.07.003]
[103]
Miyata, T.; Kurokawa, K.; van Ypersele de Strihou, C. Relevance of oxidative and carbonyl stress to long-term uremic complications. Kidney Int. Suppl., 2000, 76, S120-S125.
[http://dx.doi.org/10.1046/j.1523-1755.2000.07615.x] [PMID: 10936808]
[104]
Lee, Y.T.; Hsu, C.C.; Lin, M.H.; Liu, K.S.; Yin, M.C. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur. J. Pharmacol., 2005, 513(1-2), 145-150.
[http://dx.doi.org/10.1016/j.ejphar.2005.02.010] [PMID: 15878720]
[105]
Bao, Y.; Gao, C.; Hao, W.; Ji, C.; Zhao, L.; Zhang, J.; Liu, T.; Ma, Q. Effects of dietary l-carnosine and alpha-lipoic acid on growth performance, blood thyroid hormones and lipid profiles in finishing pigs. Asian-Australas. J. Anim. Sci., 2015, 28(10), 1465-1470.
[http://dx.doi.org/10.5713/ajas.14.0604] [PMID: 26194221]
[106]
Mong, M.C.; Chao, C.Y.; Yin, M.C. Histidine and carnosine alleviated hepatic steatosis in mice consumed high saturated fat diet. Eur. J. Pharmacol., 2011, 653(1-3), 82-88.
[http://dx.doi.org/10.1016/j.ejphar.2010.12.001] [PMID: 21167151]
[107]
Emini Veseli, B.; Perrotta, P.; De Meyer, G.R.A.; Roth, L.; Van der Donckt, C.; Martinet, W.; De Meyer, G.R.Y. Animal models of atherosclerosis. Eur. J. Pharmacol., 2017, 816, 3-13.
[http://dx.doi.org/10.1016/j.ejphar.2017.05.010] [PMID: 28483459]
[108]
Brown, B.E.; Kim, C.H.; Torpy, F.R.; Bursill, C.A.; McRobb, L.S.; Heather, A.K.; Davies, M.J.; van Reyk, D.M. Supplementation with carnosine decreases plasma triglycerides and modulates atherosclerotic plaque composition in diabetic apo E(-/-) mice. Atherosclerosis, 2014, 232(2), 403-409.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.11.068] [PMID: 24468155]
[109]
Sauerhöfer, S.; Yuan, G.; Braun, G.S.; Deinzer, M.; Neumaier, M.; Gretz, N.; Floege, J.; Kriz, W.; van der Woude, F.; Moeller, M.J. L-carnosine, a substrate of carnosinase-1, influences glucose metabolism. Diabetes, 2007, 56(10), 2425-2432.
[http://dx.doi.org/10.2337/db07-0177] [PMID: 17601992]
[110]
Freedman, B.I.; Hicks, P.J.; Sale, M.M.; Pierson, E.D.; Langefeld, C.D.; Rich, S.S.; Xu, J.; McDonough, C.; Janssen, B.; Yard, B.A.; van der Woude, F.J.; Bowden, D.W. A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end-stage renal disease in European Americans. Nephrol. Dial. Transplant., 2007, 22(4), 1131-1135.
[http://dx.doi.org/10.1093/ndt/gfl717] [PMID: 17205963]
[111]
Alkhalaf, A.; Bakker, S.J.; Bilo, H.J.; Gans, R.O.; Navis, G.J.; Postmus, D.; Forsblom, C.; Groop, P.H.; Vionnet, N.; Hadjadj, S.; Marre, M.; Parving, H.H.; Rossing, P.; Tarnow, L. A polymorphism in the gene encoding carnosinase (CNDP1) as a predictor of mortality and progression from nephropathy to end-stage renal disease in type 1 diabetes mellitus. Diabetologia, 2010, 53(12), 2562-2568.
[http://dx.doi.org/10.1007/s00125-010-1863-0] [PMID: 20711718]
[112]
Ahluwalia, T.S.; Lindholm, E.; Groop, L.C. Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes. Diabetologia, 2011, 54(9), 2295-2302.
[http://dx.doi.org/10.1007/s00125-011-2178-5] [PMID: 21573905]
[113]
Albrecht, T.; Zhang, S.; Braun, J.D.; Xia, L.; Rodriquez, A.; Qiu, J.; Peters, V.; Schmitt, C.P.; van den Born, J.; Bakker, S.J.L.; Lammert, A.; Köppel, H.; Schnuelle, P.; Krämer, B.K.; Yard, B.A.; Hauske, S.J. The CNDP1 (CTG)5 Polymorphism is associated with biopsy-proven diabetic nephropathy, time on hemodialysis, and diabetes duration. J. Diabetes Res., 2017, 2017 9506730
[http://dx.doi.org/10.1155/2017/9506730] [PMID: 28553654]
[114]
Bellia, F.; Amorini, A.M.; La Mendola, D.; Vecchio, G.; Tavazzi, B.; Giardina, B.; Di Pietro, V.; Lazzarino, G.; Rizzarelli, E. New glycosidic derivatives of histidine-containing dipeptides with antioxidant properties and resistant to carnosinase activity. Diabetologia,2007, 53(12), 2562-2568. Eur. J. Med. Chem., 2007, 43(2), 373-380.
[http://dx.doi.org/10.1016/j.ejmech.2007.03.038] [PMID: 17548130]
[115]
Vistoli, G.; Carini, M.; Aldini, G. Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs. Amino Acids, 2012, 43(1), 111-126.
[http://dx.doi.org/10.1007/s00726-012-1224-z] [PMID: 22286834]
[116]
Peters, V.; Calabrese, V.; Forsberg, E.; Volk, N.; Fleming, T.; Baelde, H.; Weigand, T.; Thiel, C.; Trovato, A.; Scuto, M.; Modafferi, S.; Schmitt, C.P. Protective actions of anserine under diabetic conditions. Int. J. Mol. Sci., 2018, 19(9) E2751
[http://dx.doi.org/10.3390/ijms19092751] [PMID: 30217069]
[117]
Peters, V.; Lanthaler, B.; Amberger, A.; Fleming, T.; Forsberg, E.; Hecker, M.; Wagner, A.H.; Yue, W.W.; Hoffmann, G.F.; Nawroth, P.; Zschocke, J.; Schmitt, C.P. Carnosine metabolism in diabetes is altered by reactive metabolites. Amino Acids, 2015, 47(11), 2367-2376.
[http://dx.doi.org/10.1007/s00726-015-2024-z] [PMID: 26081982]
[118]
Vistoli, G.; Orioli, M.; Pedretti, A.; Regazzoni, L.; Canevotti, R.; Negrisoli, G.; Carini, M.; Aldini, G. Design, synthesis, and evaluation of carnosine derivatives as selective and efficient sequestering agents of cytotoxic reactive carbonyl species. ChemMedChem, 2009, 4(6), 967-975.
[http://dx.doi.org/10.1002/cmdc.200800433] [PMID: 19301317]
[119]
Orioli, M.; Vistoli, G.; Regazzoni, L.; Pedretti, A.; Lapolla, A.; Rossoni, G.; Canevotti, R.; Gamberoni, L.; Previtali, M.; Carini, M.; Aldini, G. Design, synthesis, ADME properties, and pharmacological activities of β-alanyl-D-histidine (D-carnosine) prodrugs with improved bioavailability. ChemMedChem, 2011, 6(7), 1269-1282.
[http://dx.doi.org/10.1002/cmdc.201100042] [PMID: 21634010]
[120]
Plump, A.S.; Smith, J.D.; Hayek, T.; Aalto-Setälä, K.; Walsh, A.; Verstuyft, J.G.; Rubin, E.M.; Breslow, J.L. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell, 1992, 71(2), 343-353.
[http://dx.doi.org/10.1016/0092-8674(92)90362-G] [PMID: 1423598]
[121]
Wen, M.; Segerer, S.; Dantas, M.; Brown, P.A.; Hudkins, K.L.; Goodpaster, T.; Kirk, E.; LeBoeuf, R.C.; Alpers, C.E. Renal injury in apolipoprotein E-deficient mice. Lab. Invest., 2002, 82(8), 999-1006.
[http://dx.doi.org/10.1097/01.LAB.0000022222.03120.D4] [PMID: 12177238]
[122]
Anders, H.J.; Muruve, D.A. The inflammasomes in kidney disease. J. Am. Soc. Nephrol., 2011, 22(6), 1007-1018.
[http://dx.doi.org/10.1681/ASN.2010080798] [PMID: 21566058]
[123]
Solini, A.; Menini, S.; Rossi, C.; Ricci, C.; Santini, E.; Blasetti Fantauzzi, C.; Iacobini, C.; Pugliese, G. The purinergic 2X7 receptor participates in renal inflammation and injury induced by high-fat diet: possible role of NLRP3 inflammasome activation. J. Pathol., 2013, 231(3), 342-353.
[http://dx.doi.org/10.1002/path.4237] [PMID: 23843215]
[124]
Chalmers, J.; Cooper, M.E. UKPDS and the legacy effect. N. Engl. J. Med., 2008, 359(15), 1618-1620.
[http://dx.doi.org/10.1056/NEJMe0807625] [PMID: 18843126]
[125]
Ahshin-Majd, S.; Zamani, S.; Kiamari, T.; Kiasalari, Z.; Baluchnejadmojarad, T.; Roghani, M. Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms. Peptides, 2016, 86, 102-111.
[http://dx.doi.org/10.1016/j.peptides.2016.10.008] [PMID: 27777064]
[126]
de Courten, B.; Jakubova, M.; de Courten, M.P.; Kukurova, I.J.; Vallova, S.; Krumpolec, P.; Valkovic, L.; Kurdiova, T.; Garzon, D.; Barbaresi, S.; Teede, H.J.; Derave, W.; Krssak, M.; Aldini, G.; Ukropec, J.; Ukropcova, B. Effects of carnosine supplementation on glucose metabolism: Pilot clinical trial. Obesity (Silver Spring), 2016, 24(5), 1027-1034.
[http://dx.doi.org/10.1002/oby.21434] [PMID: 27040154]
[127]
Forsberg, E.A.; Botusan, I.R.; Wang, J.; Peters, V.; Ansurudeen, I.; Brismar, K.; Catrina, S.B. Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1. J. Endocrinol., 2015, 225(3), 159-167.
[http://dx.doi.org/10.1530/JOE-14-0571] [PMID: 25869614]
[128]
Regazzoni, L.; de Courten, B.; Garzon, D.; Altomare, A.; Marinello, C.; Jakubova, M.; Vallova, S.; Krumpolec, P.; Carini, M.; Ukropec, J.; Ukropcova, B.; Aldini, G. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect. Sci. Rep., 2016, 6, 27224.
[http://dx.doi.org/10.1038/srep27224] [PMID: 27265207]
[129]
Baye, E.; Ukropec, J.; de Courten, M.P.J.; Mousa, A.; Kurdiova, T.; Johnson, J.; Wilson, K.; Plebanski, M.; Aldini, G.; Ukropcova, B.; de Courten, B. Carnosine supplementation improves serum resistin concentrations in overweight or obese otherwise healthy adults: a pilot randomized trial. Nutrients, 2018, 10(9) E1258
[http://dx.doi.org/10.3390/nu10091258] [PMID: 30205427]
[130]
Baye, E.; Ukropec, J.; de Courten, M.P.J.; Kurdiova, T.; Krumpolec, P.; Fernández-Real, J.M.; Aldini, G.; Ukropcova, B.; de Courten, B. Carnosine supplementation reduces plasma soluble transferrin receptor in healthy overweight or obese individuals: a pilot randomised trial. Amino Acids, 2018, 51(1), 73-81.
[http://dx.doi.org/10.1007/s00726-018-2623-6] [PMID: 30136029]
[131]
Baye, E.; Ukropec, J.; de Courten, M.P.; Vallova, S.; Krumpolec, P.; Kurdiova, T.; Aldini, G.; Ukropcova, B.; de Courten, B. Effect of carnosine supplementation on the plasma lipidome in overweight and obese adults: a pilot randomised controlled trial. Sci. Rep., 2017, 7(1), 17458.
[http://dx.doi.org/10.1038/s41598-017-17577-7] [PMID: 29234057]
[132]
Anderson, E.J.; Vistoli, G.; Katunga, L.A.; Funai, K.; Regazzoni, L.; Monroe, T.B.; Gilardoni, E.; Cannizzaro, L.; Colzani, M.; De Maddis, D.; Rossoni, G.; Canevotti, R.; Gagliardi, S.; Carini, M.; Aldini, G. A carnosine analog mitigates metabolic disorders of obesity by reducing carbonyl stress. J. Clin. Invest., 2018, 128(12), 5280-5293.
[http://dx.doi.org/10.1172/JCI94307] [PMID: 30226473]
[133]
Baye, E.; Menon, K.; de Courten, M.P.; Earnest, A.; Cameron, J.; de Courten, B. Does supplementation with carnosine improve cardiometabolic health and cognitive function in patients with pre-diabetes and type 2 diabetes? study protocol for a randomised, double-blind, placebo-controlled trial. BMJ Open, 2017, 7(9) e017691
[http://dx.doi.org/10.1136/bmjopen-2017-017691] [PMID: 28864708]
[134]
Elbarbary, N.S.; Ismail, E.A.R.; El-Naggar, A.R.; Hamouda, M.H.; El-Hamamsy, M. The effect of 12 weeks carnosine supplementation on renal functional integrity and oxidative stress in pediatric patients with diabetic nephropathy: a randomized placebo-controlled trial. Pediatr. Diabetes, 2018, 19(3), 470-477.
[http://dx.doi.org/10.1111/pedi.12564] [PMID: 28744992]

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