INCREMENTO DE LA EXPRESIÓN DE TLR4 Y EFECTO ANTIOXIDANTE DEL ÁCIDO ACETILSALICÍLICO EN CONEJOS CON DIETA ALTA EN GRASAS

Autores/as

  • Ana Elenka Ortíz-Reyes Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México. Tlalnepantla, Estado de México, México
  • C. Marissa Calderón-Torres Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México. Tlalnepantla, Estado de México, México

DOI:

https://doi.org/10.29105/respyn16.2-1

Resumen

Introducción: La obesidad y el desarrollo de enfermedades hepáticas que se caracterizan por el aumento y acumulación de lípidos en tejidos y sangre, inflamación y estrés oxidante, son actualmente una epidemia mundial, y en la población mexicana es cada vez mayor el número de jóvenes afectados. Este aumento ha conducido a la investigación médica hacia la detección temprana del síndrome metabólico, que se emplea como indicador de síntomas que pueden ser de riesgo para la salud y conducir a enfermedades hepáticas. Objetivo: Los objetivos del presente trabajo fueron: evaluar en un modelo de dislipidemia en conejos jóvenes alimentados con una dieta alta en grasa (ácido palmítico al 20%), la producción de especies reactivas del oxígeno y cambios en la expresión de genes TLR4, COX2y de IL-1β como marcadores de inflamación y de estrés oxidante, así como evaluar el efecto del ácido acetilsalicílico en la producción de radicales libres y en la expresión de estos genes. Resultados: En los conejos alimentados con exceso de grasa aumentaron los niveles de triglicéridos (p<0.05), la expresión de TLR4 y las especies reactivas del oxígeno, aunque éstas últimas no de forma significativa. La administración de ácido acetilsalicílico en dosis antiinflamatorias disminuyó la producción de especies reactivas del oxígeno y la expresión de TLR4. Discusión: La ingesta elevada de grasa en conejos jóvenes por un período corto de tiempo conduce a la dislipidemia y a la sobreexpresión de TLR4, gen clave de la respuesta inflamatoria y vinculada al aumento de las especies reactivas del oxígeno. Los resultados indican que el ácido acetilsalicílico tiene efecto antioxidante.

ABSTRACT

Introduction: The obesity and liver diseases progression are characterized by the increase and accumulation of lipids in tissues and blood, inflammation and oxidative stress. These diseases are now a worldwide epidemic, and the number of young people affected is increasing in the Mexican population. This increase has led to medical research towards the early detection of the metabolic syndrome, which is used as an indicator of symptoms that may be at risk for health and lead to liver disease. Objective: The objectives of the present study were to evaluate in a model of dyslipidemia in young rabbits fed three months with a diet high in fat (20% palmitic acid), the production of reactive oxygen species and changes in TLR4, COX2 and IL-1β gene expression, as markers of inflammation and oxidative stress; also to evaluate the effect of acetylsalicylic acid on the production of free radicals and on the expression of these genes. Results: In rabbits fed with excess of fat, significantly increased the levels of triglycerides (p<0.05), TLR4 expression, and reactive oxygen species, although in the latter, not significantly. The administration of acetylsalicylic acid in anti-inflammatory doses decreased the production of reactive oxygen species and the expression of TLR4. Discussion: The high fat intake in young rabbits lead to dyslipidemia and overexpression of TLR4, a key gene in the inflammatory response and linked to the increase of reactive oxygen species. The results indicate that acetylsalicylic acid has an antioxidant effect

Palabras Clave:Obesidad, dislipidemia, inflamación, estrés oxidante, hígado graso no alcohólico (HGNA),

Obesity, dyslipidemia, inflammation, oxidative stress, non-alcoholic fatty liver (HGNA)

Descargas

Los datos de descargas todavía no están disponibles.

Métricas

Cargando métricas ...

Citas

Akarasereenont P, Bakhle YS, Thiemermann C y Vane JR. (1995). Cytokine-mediated induction of cyclo-oxygenase-2 by activation of tyrosine kinase in bovine endothelial cells stimulated by bacterial lipopolysaccharide. British Journal of Pharmacology; 115: 401-408. DOI: https://doi.org/10.1111/j.1476-5381.1995.tb16347.x

Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman J, Donato KA, Fruchart J, James W, Loria CM, Smith SC Jr. (2009). Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120: 1640–1645. DOI: https://doi.org/10.1161/CIRCULATIONAHA.109.192644

Ayyadevara S, Bharill P, Dandapat A, Hu C, Khaidakov M, Mitra S, Shmooklwe Reis RJ y Mehta JL. (2013). Aspirin Inhibits Oxidant Stress, Reduces Age-Associated Functional Declines, and Extends Lifespan of Caenorhabditis elegans. Antioxidants & Redox Signaling; 18 (5):481-490. DOI: https://doi.org/10.1089/ars.2011.4151

Battaglia V, Salvi M y Toninello A. (2005). Oxidative stress is responsible for mitochondrial permeability transition induction by salicylate in liver mitochondria. Journal of Biological Chemistry; 280(40): 33864-33872. DOI: https://doi.org/10.1074/jbc.M502391200

Calderón M, Peña A y Thomé PE. (2006). DhARO4, an amino acid biosynthetic gene, is stimulated by high salinity in Debaryomyces hansenii. Yeast; (23):725–734. DOI: https://doi.org/10.1002/yea.1384

Cardoso AR, Kakimoto PA y Kowaltowski AJ. (2013). Diet-Sensitive Sources of Reactive Oxygen Species in Liver Mitochondria: Role of Very Long Chain Acyl-CoA Deshydrogenases. PLOS ONE; 8 (10): e77088. DOI: https://doi.org/10.1371/journal.pone.0077088

Clària J, Lee MH y Serhan CN. (1996). Aspirin-Triggered Lipoxins (15-epi-LX) Are Generated by the Human Lung Adenocarcinoma Cell Line (A549)- Neutrophil Interactions and Are Potent Inhibitors of Cell Proliferation. Molecular Medicine; 2(5):583-596. DOI: https://doi.org/10.1007/BF03401642

Cyrus T, Sung S, Zhao L, Funk CD, Tang S y Praticò D. (2002). Effect of Low-Dose Aspirin on Vascular Inflammation, Plaque Stability, and Atherogenesis in Low Density Lipoprotein Receptor-Deficient Mice. Circulation; 106:1282-1287. DOI: https://doi.org/10.1161/01.CIR.0000027816.54430.96

Chen S, Lin G, Lei L, You X, Wu C, Xu W, Huang M, Luo L, Wang Z, Li Y, Zhao X, y Yan F. (2013). Hyperlipidemia Modifies Innate Immune Responses to Lipopolysaccharide via the TLR-NF-κB Signaling Pathway. Inflammation; 36(4): 968-976. DOI: https://doi.org/10.1007/s10753-013-9628-9

Fang D, Yang S, Quan W, Jia H, Quan Z y Qu Z. (2014). Atorvastatin suppresses Toll-like receptor 4 expression y NF-kB activation in rabbit atherosclerotic plaques. European Review for Medical and Pharmacological Sciences; (18): 242-246.

Fields M, Lewis CG y Bureau I. (2001). Aspirin Reduces Blood Cholesterol in Copper-Deficient Rats: A Potential Antioxidant Agent? Metabolism; 50(5): 558-561. DOI: https://doi.org/10.1053/meta.2001.22513

Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, y Shimomura I. (2004). Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest; 114(12):1752-1761. DOI: https://doi.org/10.1172/JCI21625

Gou J y Friedman SL. (2010). Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis. Fibrogenesis & Tissue Repair; (3):21. DOI: https://doi.org/10.1186/1755-1536-3-21

Hempel SL, Buettner GR, O´Malley YQ, Wessels DA, y Flaherty DM. (1999). DihydrofluoresceinDiacetate is superior for detecting intracellular oxidants: Comparision with 2’7’ Dichlorodihydrofluorescein diacetate, 5 (and 6)-Carboxy-2’7’ Dichlorodihydrofluorescein diacetate and Dihydrorhodamine 123. Free Radical Biology & Medicine; 27(1-2): 146–159. DOI: https://doi.org/10.1016/S0891-5849(99)00061-1

Hsieh PS, Jin JS, Chiang CF, Chan PC, Chen CH y Shih KC. (2009). COX-2-mediated Inflammation in Fat Is Crucial for Obesity-linked Insulin Resistance and Fatty Liver. Obesity; (17): 1150–1157. DOI: https://doi.org/10.1038/oby.2008.674

Integrated DNA Technologies. (2017). www.idtdna.com/pages. Obtenido de https://www.idtdna.com/calc/analyzer

Kibbe, W. (2007). OligoCalc: an online oligonucleotide properties calculator. Obtenido de http://biotools.nubic.northwestern.edu/OligoCalc.html DOI: https://doi.org/10.1093/nar/gkm234

Kourtis N y Tavernarakis N. (2011). Cellular stress response pathways and ageing: intricate molecular relationships. EMBO Journal; (30): 2520–2531. DOI: https://doi.org/10.1038/emboj.2011.162

Lee JY, Ye J, Gao Z, Youn H, Lee WH, Zhao L, Sizemore N y Hwang DH. (2003). Reciprocal Modulation of Toll-like Receptor-4 Signaling Pathways Involving MyD88 and Phosphatidylinositol 3-Kinase/AKT by Saturated and Polyunsaturated Fatty Acids. The Journal of Biological Chemistry; 278 (39): 37041–37051. DOI: https://doi.org/10.1074/jbc.M305213200

Liu J, Zhuang ZJ, Bian D, Ma XJ, Xun YH, Yang WJ, Lou Y, Liu YL, Jia L, Wang Y, Zhu M, Ye DW, Zhou G, Lou GQ y Shi JP. (2014). Toll-like receptor-4 signalling in the progression of non-alcoholic fatty liver disease induced by high-fat and high-fructose diet in mice. Clinical and Experimental Pharmacology and Physiology; (41):482-488. DOI: https://doi.org/10.1111/1440-1681.12241

Mahmood KA, Ahmed JH y Jawad AM. (2009). Non-stereroidal anti-inflammatory drugs (NSAIDS), free radicals and reactive oxygen species (ROS): A review of literature. The Medical Journal of Basrah University; 27(1):46-53. DOI: https://doi.org/10.33762/mjbu.2009.49041

Manček-Keber M, Frank-Bertoncelj M, Hafner-Bratkovič I, Smole A, Zorko M, Pirher N, Hayer S, Kralj-Iglič V, Rozman B, Ilc N, Horvat S y Jerala R. (2015). Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles. Science Signaling; 8(381): 1-12. DOI: https://doi.org/10.1126/scisignal.2005860

McRae MP. (2008). Vitamin C supplementation lowers serum low-density lipoprotein cholesterol and triglycerides: a meta-analysis of 13 randomized controlled. Journal of Chiropractic Medicine; (7); 48–58. DOI: https://doi.org/10.1016/j.jcme.2008.01.002

Milagro FI, Javier Campión J, y Martínez JA. (2006). Weight Gain Induced by High-Fat Feeding

Involves Increased Liver Oxidative Stress. Obesity; 14(7): 1118-1123.

Oliveira CP, da Costa Gayotto LC, Tatai C, Della Bina BI, Janiszewski M, Lima ES, Abdalla DS, Lopasso FP, Laurindo FR y Laudanna AA. (2002). Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease, in rats fed with a choline-deficient diet. J Cell Mol Med; 6 (3): 399-406. DOI: https://doi.org/10.1111/j.1582-4934.2002.tb00518.x

Pagadala M, Zein CO y McCullough AJ. (2009). Predictors of Steatohepatitis and Advanced Fibrosis in Non-Alcoholic Fatty Liver Disease. Clin Liver Dis; (13): 591–606. DOI: https://doi.org/10.1016/j.cld.2009.07.011

Paul-Clark MJ, Van Cao T, Moradi-Bidhendi N, Cooper D y Gilory DW. (2004). 15-epi-lipoxin A4-mediated Induction of Nitric Oxide Explains How Aspirin Inhibits Acute Inflammation. J Expe Med; 200(1):69-78. DOI: https://doi.org/10.1084/jem.20040566

Petrosillo G, Portincasa P, Grattagliano I, Casanova G, Matera M, Ruggiero FM, Ferri y Paradies G. (2007). Mitochondrial dysfunction in rat with nonalcoholic fatty liver Involvemet of complex I, reactive oxygen species and cardiolipin. Biochimica et Biophysica Acta; (1726):1260-1267. DOI: https://doi.org/10.1016/j.bbabio.2007.07.011

Podhaisky HP, Abate A, Polte T, Oberle OS y Schröder H. (1997). Aspirin protects endothelial cells from oxidative stress - possible synergism with vitamin E. FEBS Letters; (417): 349-351. DOI: https://doi.org/10.1016/S0014-5793(97)01307-0

Ricciotti E y FitzGerald GA. (2011). Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol; 31(5): 986-1000. DOI: https://doi.org/10.1161/ATVBAHA.110.207449

Schmitt ME, Brown TA y Trumpower BL (1990) A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae. Nucleic Acids Res; (18):3091-3092. DOI: https://doi.org/10.1093/nar/18.10.3091

Song J, Ke SF, Zhou CC, Zhang SL, Guan YF, Xu TY, Sheng CQ, Wang P y Miao CY. (2013). Nicotinamide Phosphoribosyltransferase Is Required for the Calorie Restriction–Mediated Improvements in Oxidative Stress, Mitochondrial Biogenesis, and Metabolic Adaptation. J Gerontol A Biol Sci Med Sci; 69(1):44–57. DOI: https://doi.org/10.1093/gerona/glt122

Stojsavljević S, Gomerčić Palčić M, Virović Jukić L, Smirčić Duvnjak L y Duvnjak M. (2014). Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World Journal of Gastroenterology; 20(28):18070-18091. DOI: https://doi.org/10.3748/wjg.v20.i48.18070

Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuari S, Kotani H, Yamaoka S, Miyake K, Aoe S, Kamei Y y Ogawa Y. (2007). Role of the Toll-like Receptor 4/NF-kappaB Pathway in Saturad Fatty Acid-Induced Inflammatory Changes in the Interaction Between Adipocytes and Macrophages. Arterioscler Thromb Vasc Biol. 27(1):84-91. DOI: 10.1161/01 DOI: https://doi.org/10.1161/01.ATV.0000251608.09329.9a

Tilg H. (2010). The Role of Cytokines in Non-Alcoholic Fatty Liver Disease. Digestive Diseases; 28(1): 179-185. DOI: https://doi.org/10.1159/000282083

Untergasser A, C. K.-S. (2012). Primer3-new capabilities and interfaeces. Obtenido de bioinfo.ut.ee: http://bioinfo.ut.ee/primer3-0.4.0/

Yu J, Ip E, De la Peña A, Hou JY, Sesha J, Pera N, Hall P, Kirsh R, Leclerq I y Farrell C. (2006). COX-2 Induction in Mice With Experimental Nutritional Steotohepatitis: Role as Pro-inflammatory Mediator. Hepatology; 43(4): 286-386. DOI: https://doi.org/10.1002/hep.21108

Descargas

Publicado

2017-07-10

Cómo citar

Ortíz-Reyes, A. E., & Calderón-Torres, C. M. (2017). INCREMENTO DE LA EXPRESIÓN DE TLR4 Y EFECTO ANTIOXIDANTE DEL ÁCIDO ACETILSALICÍLICO EN CONEJOS CON DIETA ALTA EN GRASAS. RESPYN Revista Salud Pública Y Nutrición, 16(2), 1–10. https://doi.org/10.29105/respyn16.2-1

Número

Sección

Artículo Original