Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Research Article

Lactose and Casein Cause Changes on Biomarkers of Oxidative Damage and Dysbiosis in an Experimental Model of Multiple Sclerosis

Author(s): Begoña M. Escribano*, Ana Muñoz-Jurado*, Evelio Luque, Cristina Conde*, Montse Feijóo, Manuel LaTorre, Manuel E. Valdelvira, Paula Buendía, Ana I. Giraldo, Javier Caballero-Villarraso, Abel Santamaría, Eduardo Agüera and Isaac Túnez*

Volume 21, Issue 8, 2022

Published on: 11 January, 2022

Page: [680 - 692] Pages: 13

DOI: 10.2174/1871527320666211207101113

Price: $65

conference banner
Abstract

Background and Objectives: Experimental Autoimmune Encephalomyelitis (EAE) in rats closely reproduces Multiple Sclerosis (MS), a disease characterized by neuroinflammation and oxidative stress that also appears to extend to other organs and their compartments. The origin of MS is a matter for discussion, but it would seem that altering certain bacterial populations present in the gut may lead to a proinflammatory condition due to the bacterial Lipopolysaccharides (LPS) in the so-called brain-gut axis. The casein and lactose in milk confer anti-inflammatory properties and immunomodulatory effects. The objectives of this study were to evaluate the effects of administration of casein and lactose on the oxidative damage and the clinical status caused by EAE and to verify whether both casein and lactose had any effect on the LPS and its transport protein -LBP-.

Methods: Twenty male Dark Agouti rats were divided into control rats (control), EAE rats, and EAE rats, to which casein and lactose, EAE+casein, and EAE+lactose, respectively, were administered. Fifty-one days after casein and lactose administration, the rats were sacrificed, and different organs were studied (brain, spinal cord, blood, heart, liver, kidney, small, and large intestine). In the latter, products derived from oxidative stress were studied (lipid peroxides and carbonylated proteins) as well as the glutathione redox system, various inflammation factors (total nitrite, Nuclear Factor-kappa B p65, the Rat Tumour Necrosis Factor-α), and the LPS and LBP values.

Results and Conclusion: Casein and lactose administration improved the clinical aspect of the disease at the same time as reducing inflammation and oxidative stress, exerting its action on the glutathione redox system, or increasing GPx levels.

Keywords: Bacterial lipopolysaccharide, casein, experimental autoimmune encephalomyelitis, glutathione redox system, lactose, multiple sclerosis.

Graphical Abstract
[1]
Chatterton DE, Nguyen DN, Bering SB, Sangild PT. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns. Int J Biochem Cell Biol 2013; 45(8): 1730-47.
[http://dx.doi.org/10.1016/j.biocel.2013.04.028] [PMID: 23660296]
[2]
Kanwar JR, Kanwar RK, Sun X, et al. Molecular and biotechnological advances in milk proteins in relation to human health. Curr Protein Pept Sci 2009; 10(4): 308-38.
[http://dx.doi.org/10.2174/138920309788922234] [PMID: 19689355]
[3]
Otaegui D, Mostafavi S, Bernard CCA, et al. Increased transcriptional activity of milk-related genes following the active phase of experimental autoimmune encephalomyelitis and multiple sclerosis. J Immunol 2007; 179(6): 4074-82.
[http://dx.doi.org/10.4049/jimmunol.179.6.4074] [PMID: 17785846]
[4]
Monnai M, Otani H. Effect of bovine β-caseinoglycopeptide on secretion of interleukin-1 family cytokines by P3888D1 cells, a line derived from mouse monocyte/macrophage. Milchwissenschaft 1997; 52: 192-6.
[5]
Otani H, Watanabe T, Tashiro Y. Effects of bovine beta-casein (1-28) and its chemically synthesized partial fragments on proliferative responses and immunoglobulin production in mouse spleen cell cultures. Biosci Biotechnol Biochem 2001; 65(11): 2489-95.
[http://dx.doi.org/10.1271/bbb.65.2489] [PMID: 11791723]
[6]
Daddaoua A, Puerta V, Zarzuelo A, Suárez MD, Sánchez de Medina F, Martínez-Augustin O. Bovine glycomacropeptide is anti-inflammatory in rats with hapten-induced colitis. J Nutr 2005; 135(5): 1164-70.
[http://dx.doi.org/10.1093/jn/135.5.1164] [PMID: 15867298]
[7]
Li EW, Mine Y. Immunoenhancing effects of bovine glycomacropeptide and its derivatives on the proliferative response and phagocytic activities of human macrophagelike cells, U937. J Agric Food Chem 2004; 52(9): 2704-8.
[http://dx.doi.org/10.1021/jf0355102] [PMID: 15113179]
[8]
Winer S, Astsaturov I, Cheung RK, et al. T cells of multiple sclerosis patients target a common environmental peptide that causes encephalitis in mice. J Immunol 2001; 166(7): 4751-6.
[http://dx.doi.org/10.4049/jimmunol.166.7.4751] [PMID: 11254737]
[9]
Sotgiu S, Arru G, Fois ML, et al. Immunomodulation of fucosyl-lactose and lacto-N-fucopentaose on mononuclear cells from multiple sclerosis and healthy subjects. Int J Biomed Sci 2006; 2(2): 114-20.
[PMID: 23674973]
[10]
Toscano M, De Grandi R, Grossi E, Drago L. Role of the human breast milk-associated microbiota on the newborns’ immune system: A mini review. Front Microbiol 2017; 8: 2100.
[http://dx.doi.org/10.3389/fmicb.2017.02100] [PMID: 29118752]
[11]
Constantinescu CS, Farooqi N, O’Brien K, Gran B. Experimental Autoimmune Encephalomyelitis (EAE) as a model for Multiple Sclerosis (MS). Br J Pharmacol 2011; 164(4): 1079-106.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01302.x] [PMID: 21371012]
[12]
Medina-Fernández FJ, Luque E, Aguilar-Luque M, et al. Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in experimental autoimmune encephalomyelitis. Life Sci 2017; 169: 20-6.
[http://dx.doi.org/10.1016/j.lfs.2016.11.011] [PMID: 27876534]
[13]
Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Ann Neurol 2000; 47(6): 707-17.
[http://dx.doi.org/10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q] [PMID: 10852536]
[14]
Ochoa-Repáraz J, Mielcarz DW, Begum-Haque S, Kasper LH. Gut, bugs, and brain: role of commensal bacteria in the control of central nervous system disease. Ann Neurol 2011; 69(2): 240-7.
[http://dx.doi.org/10.1002/ana.22344] [PMID: 21387369]
[15]
Wekerle H, Berer K, Krishnamoorthy G. Remote control-triggering of brain autoimmune disease in the gut. Curr Opin Immunol 2013; 25(6): 683-9.
[http://dx.doi.org/10.1016/j.coi.2013.09.009] [PMID: 24161654]
[16]
Escribano BM, Medina-Fernández FJ, Aguilar-Luque M, et al. Lipopolysaccharide binding protein and oxidative stress in a multiple sclerosis model. Neurotherapeutics 2017; 14(1): 199-211.
[http://dx.doi.org/10.1007/s13311-016-0480-0] [PMID: 27718209]
[17]
Stosic-Grujicic S, Ramic Z, Bumbasirevic V, Harhaji L, Mostarica-Stojkovic M. Induction of experimental autoimmune encephalomyelitis in Dark Agouti rats without adjuvant. Clin Exp Immunol 2004; 136(1): 49-55.
[http://dx.doi.org/10.1111/j.1365-2249.2004.02418.x] [PMID: 15030513]
[18]
Halperin R, Shinnar N, Kronfeld-Schor N, Hadas E. Effect of intrauterine injection of casein on fetal survival in rat: A new pharmacological approach for contraception. Contraception 2006; 73(6): 641-4.
[http://dx.doi.org/10.1016/j.contraception.2005.11.002] [PMID: 16730499]
[19]
Leichter J, Goda T, Bhandari SD, Bustamante S, Koldovský O. Relation between dietary-induced increase of intestinal lactase activity and lactose digestion and absorption in adult rats. Am J Physiol 1984; 247(6 Pt 1): G729-35.
[PMID: 6439052]
[20]
Pérez-Nievas BG, García-Bueno B, Madrigal JL, Leza JC. Chronic immobilisation stress ameliorates clinical score and neuroinflammation in a MOG-induced EAE in Dark Agouti rats: mechanisms implicated. J Neuroinflammation 2010; 7: 60.
[http://dx.doi.org/10.1186/1742-2094-7-60] [PMID: 20929574]
[21]
Flohé L, Günzler WA. Assays of glutathione peroxidase. Methods Enzymol 1984; 105: 114-21.
[http://dx.doi.org/10.1016/S0076-6879(84)05015-1] [PMID: 6727659]
[22]
Levine RL, Garland D, Oliver CN, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990; 186: 464-78.
[http://dx.doi.org/10.1016/0076-6879(90)86141-H] [PMID: 1978225]
[23]
Ricart-Jané D, Llobera M, López-Tejero MD. Anticoagulants and other preanalytical factors interfere in plasma nitrate/nitrite quantification by the Griess method. Nitric Oxide 2002; 6(2): 178-85.
[http://dx.doi.org/10.1006/niox.2001.0392] [PMID: 11890742]
[24]
Escribano BM, Luque E, Aguilar-Luque M, et al. Dose-dependent S-allyl cysteine ameliorates multiple sclerosis disease-related pathology by reducing oxidative stress and biomarkers of dysbiosis in experimental autoimmune encephalomyelitis. Eur J Pharmacol 2017; 815: 266-73.
[http://dx.doi.org/10.1016/j.ejphar.2017.09.025] [PMID: 28939293]
[25]
Conde C, Escribano BM, Luque E, et al. The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat. Nutr Neurosci 2020; 23(1): 37-48.
[http://dx.doi.org/10.1080/1028415X.2018.1469281] [PMID: 29730972]
[26]
Ravelli KG, Santos GD, Dos Santos NB, et al. Nox2-dependent Neuroinflammation in An EAE Model of Multiple Sclerosis. Transl Neurosci 2019; 10: 1-9.
[http://dx.doi.org/10.1515/tnsci-2019-0001] [PMID: 30984416]
[27]
Conde C, Escribano BM, Luque E, et al. Extra-virgin olive oil modifies the changes induced in non-nervous organs and tissues by experimental autoimmune encephalomyelitis models. Nutrients 2019; 11(10): E2448.
[http://dx.doi.org/10.3390/nu11102448] [PMID: 31615022]
[28]
Greco A, Minghetti L, Sette G, Fieschi C, Levi G. Cerebrospinal fluid isoprostane shows oxidative stress in patients with multiple sclerosis. Neurology 1999; 53(8): 1876-9.
[http://dx.doi.org/10.1212/WNL.53.8.1876] [PMID: 10563647]
[29]
Ferretti G, Bacchetti T, Principi F, et al. Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: A relationship with paraoxonase activity. Mult Scler 2005; 11(6): 677-82.
[http://dx.doi.org/10.1191/1352458505ms1240oa] [PMID: 16320727]
[30]
van de Heijning BJM, Kegler D, Schipper L, Voogd E, Oosting A, van der Beek EM. Acute and chronic effects of dietary lactose in adult rats are not explained by residual intestinal lactase activity. Nutrients 2015; 7(7): 5542-55.
[http://dx.doi.org/10.3390/nu7075237] [PMID: 26184291]
[31]
Pastuszka R, Barłowska J, Litwińczuk Z. Allergenicity of milk of different animal species in relation to human milk. Postepy Hig Med Dosw 2016; 70(0): 1451-9.
[http://dx.doi.org/10.5604/17322693.1227842] [PMID: 28100852]
[32]
Oak SJ, Jha R. The effects of probiotics in lactose intolerance: A systematic review. Crit Rev Food Sci Nutr 2019; 59(11): 1675-83.
[http://dx.doi.org/10.1080/10408398.2018.1425977] [PMID: 29425071]
[33]
Gruzelle V, Juchet A, Martin-Blondel A, Michelet M, Chabbert-Broue A, Didier A. Benefits of baked milk oral immunotherapy in French children with cow’s milk allergy. Pediatr Allergy Immunol 2020; 31(4): 364-70.
[http://dx.doi.org/10.1111/pai.13216] [PMID: 31943363]
[34]
Campbell AK, Waud JP, Matthews SB. The molecular basis of lactose intolerance. Sci Prog 2009; 92(Pt 3-4): 241-87.
[http://dx.doi.org/10.3184/003685009X12547510332240] [PMID: 19960866]
[35]
Szilagyi A, Xue X. Geographic associations between lactase phenotype, multiple sclerosis, and inflammatory bowel diseases; Does obesity trump geography? Med Hypotheses 2016; 96: 68-72.
[http://dx.doi.org/10.1016/j.mehy.2016.10.001] [PMID: 27959280]
[36]
Ibrahim HM, Mohammed-Geba K, Tawfic AA, El-Magd MA. Camel milk exosomes modulate cyclophosphamide-induced oxidative stress and immuno-toxicity in rats. Food Funct 2019; 10(11): 7523-32.
[http://dx.doi.org/10.1039/C9FO01914F] [PMID: 31674611]
[37]
Khan IT, Nadeem M, Imran M, Ullah R, Ajmal M, Jaspal MH. Antioxidant properties of Milk and dairy products: A comprehensive review of the current knowledge. Lipids Health Dis 2019; 18(1): 41.
[http://dx.doi.org/10.1186/s12944-019-0969-8] [PMID: 30717735]
[38]
Carthy TLM, Kerry JP, Kerry JF, Lynch PB, Buckley DJX. Evaluation of the antioxidant potential of natural food/plant extracts as compared with synthetic antioxidants and vitamin E in raw and cooked pork patties. Meat Sci 2015; 1: 45-52.
[39]
Chen J, Lindmark-Mansson H, Akesson B. Optimisation of a coupled enzymatic assay of glutathione peroxidase activity in bovine milk and whey. Int Dairy J 2000; 347-51.
[http://dx.doi.org/10.1016/S0958-6946(00)00057-1]
[40]
Seoane RG, Garcia-Recio V, Garrosa M, et al. Human health effects of lactose consumption as food and drug ingredient. Curr Pharm Des 2020; 26(16): 1778-89.
[http://dx.doi.org/10.2174/1381612826666200212114843] [PMID: 32048961]
[41]
Lee A, Pontin MCF, Kosmerl E, Jimenez-Flores R, Moretti DB, Ziouzenkova O. Assessment of adipogenic, antioxidant, and anti-inflammatory properties of whole and whey bovine colostrum. J Dairy Sci 2019; 102(10): 8614-21.
[http://dx.doi.org/10.3168/jds.2019-16509] [PMID: 31351710]
[42]
Pan LL, Deng YY, Wang R, et al. Lactose induces phenotypic and functional changes of neutrophils and macrophages to alleviate acute pancreatitis in mice. Front Immunol 2018; 9: 751.
[http://dx.doi.org/10.3389/fimmu.2018.00751] [PMID: 29719535]
[43]
Ochoa-Repáraz J, Mielcarz DW, Ditrio LE, et al. Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol 2009; 183(10): 6041-50.
[http://dx.doi.org/10.4049/jimmunol.0900747] [PMID: 19841183]
[44]
Berer K, Mues M, Koutrolos M, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature 2011; 479(7374): 538-41.
[http://dx.doi.org/10.1038/nature10554] [PMID: 22031325]
[45]
Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2011; 108(Suppl. 1): 4615-22.
[http://dx.doi.org/10.1073/pnas.1000082107] [PMID: 20660719]
[46]
Buscarinu MC, Romano S, Mechelli R, et al. Intestinal permeability in relapsing-remitting multiple sclerosis. Neurotherapeutics 2018; 15(1): 68-74.
[http://dx.doi.org/10.1007/s13311-017-0582-3] [PMID: 29119385]
[47]
Mielcarz DW, Kasper LH. The gut microbiome in multiple sclerosis. Curr Treat Options Neurol 2015; 17(4): 344.
[http://dx.doi.org/10.1007/s11940-015-0344-7] [PMID: 25843302]
[48]
Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 2016; 7: 12015.
[http://dx.doi.org/10.1038/ncomms12015] [PMID: 27352007]
[49]
Chen J, Chia N, Kalari KR, et al. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Sci Rep 2016; 6: 28484.
[http://dx.doi.org/10.1038/srep28484] [PMID: 27346372]
[50]
Buscarinu MC, Cerasoli B, Annibali V, et al. Altered intestinal permeability in patients with relapsing-remitting multiple sclerosis: A pilot study. Mult Scler 2017; 23(3): 442-6.
[http://dx.doi.org/10.1177/1352458516652498] [PMID: 27270497]
[51]
Caballero-Villarraso J, Galván A, Escribano BM, Túnez I. Interrelationships among gut microbiota and host: Paradigms, role in neurodegenerative diseases and future prospects. CNS Neurol Disord Drug Targets 2017; 16(8): 945-64.
[PMID: 28714393]
[52]
Guarner F. Hygiene, microbial diversity and immune regulation. Curr Opin Gastroenterol 2007; 23(6): 667-72.
[http://dx.doi.org/10.1097/MOG.0b013e3282eeb43b] [PMID: 17906445]
[53]
Veldhoen M, Hirota K, Westendorf AM, et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 2008; 453(7191): 106-9.
[http://dx.doi.org/10.1038/nature06881] [PMID: 18362914]
[54]
Cani PD, Delzenne NM. The role of the gut microbiota in energy metabolism and metabolic disease. Curr Pharm Des 2009; 15(13): 1546-58.
[http://dx.doi.org/10.2174/138161209788168164] [PMID: 19442172]
[55]
Masarwi M, Solnik HI, Phillip M, et al. Food restriction followed by refeeding with a casein- or whey-based diet differentially affects the gut microbiota of pre-pubertal male rats. J Nutr Biochem 2018; 51: 27-39.
[http://dx.doi.org/10.1016/j.jnutbio.2017.08.014] [PMID: 29091812]
[56]
Yuan Q, Zhan B, Chang R, Du M, Mao X. Antidiabetic effect of casein glycomacropeptide hydrolysates on high-fat diet and STZ-induced diabetic mice via regulating insulin signaling in skeletal muscle and modulating gut microbiota. Nutrients 2020; 12(1): E220.
[http://dx.doi.org/10.3390/nu12010220] [PMID: 31952248]
[57]
Hu X, Zhong Y, Lambers TT, Jiang W. Anti-inflammatory activity of extensively hydrolyzed casein is mediated by granzyme B. Inflamm Res 2019; 68(8): 715-22.
[http://dx.doi.org/10.1007/s00011-019-01254-8] [PMID: 31168680]
[58]
Palmeira P, Carneiro-Sampaio M. Immunology of breast milk. Rev Assoc Med Bras 2016; 62(6): 584-93.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy