Palabras clave
desnutrición
material particulado
macrófagos alveolares
vasculatura
metabolismo oxidativo
citoquinas
Cómo citar
Resumen
Introducción: La desnutrición y la contaminación del aire causan graves problemas de salud pública a nivel mundial, y los niños son una de las subpoblaciones más vulnerables. Sin embargo, los mecanismos que vinculan estos dos estresores no han sido aún dilucidados. Investigamos el efecto de la exposición a cenizas residuales del petróleo (ROFA) en la respuesta inmune pulmonar y en la vasculatura, en un modelo de desnutrición crónica (DC). Métodos: Durante 4 semanas, ratas macho destetadas fueron alimentadas con una dieta restringida al 20 % (DC) o ad libitum (control-C). DC y C se instilaron intranasalmente con (1 mg/kg de peso corporal ) ROFA. 24 h después de la exposición. Se evaluaron en cultivo de macrófagos alveolares (MA): viabilidad celular, actividad fagocítica, respuesta oxidativa y citoquinas proinflamatorias. En la aorta torácica, se evaluaron CYP1A1, eNOS, TGFβ1, canal de calcio tipo L e IL-6, IL-10 y parámetros contráctiles. Resultados: La respuesta de MA-DC a ROFA mostró cambios en el metabolismo oxidativo y la producción de citoquinas que afectan sustancialmente la respuesta inmune. La exposición a ROFA aumentó los niveles de CYP1A1 y TGF-β1 y disminuyó los niveles de eNOS y de canales de calcio en la vasculatura. La capacidad contráctil y la relajación disminuyeron en ratas DC. Conclusión: En general, los animales DC no lograron estimular la respuesta inflamatoria y desintoxicante a ROFA. Asimismo, provocó un aumento en la resistencia vascular y una disminución en la distensibilidad de la aorta, lo que podría, consecuentemente, provocar episodios agudos de insuficiencia cardiovascular en escenarios de contaminación ambiental.
Citas
Swinburn BA, Kraak VI, Allender S, Atkins VJ, Baker PI, Bogard JR et al. The Global Syndemic of Obesity, Undernutrition, and Climate Change: The Lancet Commission report. Lancet. 2019;393(10173):791-846.
https://doi.org/10.1016/S0140-6736(18)32822-8
Organización Mundial de la Salud. Malnutrición. [Internet]. OMS. 2021 Jun 9. [Consultado 10 Abril 2022]. Disponible en: https://www.who.int/news-room/fact-sheets/detail/malnutrition
Ministerio de Salud y Desarrollo Social de la Nación. 2° Encuesta Nacional de Nutrición y Salud (ENNYS 2). Resumen ejecutivo 2019. [Internet]. Argentina: Ministerio de Salud y Desarrollo Social de la Nación. Septiembre 2019. [Consultado 10 Abril 2022]. Disponible en: https://bancos.salud.gob.ar/sites/default/files/2020-01/encuesta-nac-nutricion-salud_resumen-ejecutivo.pdf
Ministerio de Salud de la Nación. Encuesta Nacional de Nutrición y Salud (ENNyS). [Internet]. Argentina: Ministerio de Salud y Desarrollo Social de la Nación. 2007. [Consultado 10 Abril 2022]. Disponible en: https://bancos.salud.gob.ar/recurso/encuesta-nacional-de-nutricion-y-saluddocumento-de-resultados-2007
Friedman SM, Rodríguez PN, Olivera MI, Bozzini C, Norese F, Gamba CA et al. Enanismo por desnutricion: cronodinamia de los procesos metabólicos en ratas. Medicina (B Aires). 1998;58(3):282-6.
Lifshitz F, Pintos PM, Lezón CE, Macri EV, Friedman SM, Boyer PM. Dyslipidemia is not associated with cardiovascular disease risk in an animal model of mild chronic suboptimal nutrition. Nutr Res. 2012;32(1):52-8.
https://doi.org/10.1016/j.nutres.2011.11.002
Sahebjami H. Nutrition and lung structure and function. Exp Lung Res. 1993;19(2):105-24.
https://doi.org/10.3109/01902149309031714
8. Arbex MA, Santos Ude P, Martins LC, Saldiva PH, Pereira LA, Braga AL. Air pollution and the respiratory system. J Bras Pneumol. 2012;38(5):643-55.
https://doi.org/10.1590/S1806-37132012000500015
World Health Organization. Regional Office for Europe. Air quality guidelines: global update 2005: particulate matter, ozone, nitrogen dioxide and sulfur dioxide. [Internet]. Copenhagen: World Health Organization. Regional Office for Europe; 2006 [Consultado 10 Abril 2022]. Disponible en: https://apps.who.int/iris/handle/10665/107823
Martin S, Dawidowski L, Mandalunis P, Cereceda-Balic F, Tasat DR. Characterization and biological effect of Buenos Aires urban air particles on mice lungs. Environ Res. 2007;105(3):340-9.
https://doi.org/10.1016/j.envres.2007.04.009
Loomis D, Grosse Y, Lauby-Secretan B, El Ghissassi F, Bouvard V, Benbrahim- Tallaa L et al. International Agency for Research on Cancer Monograph Working Group IARC. The carcinogenicity of outdoor air pollution. Lancet Oncol. 2013;14(13):1262-3.
https://doi.org/10.1016/S1470-2045(13)70487-X
González-Flecha B. Oxidant mechanisms in response to ambient air particles. Mol Aspects Med. 2004;25(1-2):169-82.
https://doi.org/10.1016/j.mam.2004.02.017
Hiraiwa K, van Eeden SF. Contribution of lung macrophages to the inflammatory responses induced by exposure to air pollutants. Mediators Inflamm. 2013;2013:619523.
https://doi.org/10.1155/2013/619523
Zhang H, Liu H, Davies KJ, Sioutas C, Finch CE, Morgan TE et al. Nrf2- regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments. Free Radic Biol Med. 2012;52(9):2038-46. Erratum in: Free Radic Biol Med. 2014;77:388.
https://doi.org/10.1016/j.freeradbiomed.2012.02.042
Churg A, Xie C, Wang X, Vincent R, Wang RD. Air pollution particles activate NF-kappaB on contact with airway epithelial cell surfaces. Toxicol Appl Pharmacol. 2005;208(1):37-45.
https://doi.org/10.1016/j.taap.2005.01.013
Pope CA 3rd, Bhatnagar A, McCracken JP, Abplanalp W, Conklin DJ, O'Toole T. Exposure to Fine Particulate Air Pollution Is Associated With Endothelial Injury and Systemic Inflammation. Circ Res. 2016;119(11):1204-1214.
https://doi.org/10.1161/CIRCRESAHA.116.309279
Brook RD, Urch B, Dvonch JT, Bard RL, Speck M, Keeler G et al. Insights into the mechanisms and mediators of the effects of air pollution exposure on blood pressure and vascular function in healthy humans. Hypertension. 2009;54(3):659-67.
https://doi.org/10.1161/HYPERTENSIONAHA.109.130237
Lenters V, Uiterwaal CS, Beelen R, Bots ML, Fischer P, Brunekreef B et al. Long-term exposure to air pollution and vascular damage in young adults. Epidemiology. 2010;21(4):512-20.
https://doi.org/10.1097/EDE.0b013e3181dec3a7
Salvi SS, Kumar A, Puri H, Bishnoi S, Asaf BB, Ghorpade D et al. Association between air pollution, body mass index, respiratory symptoms, and asthma among adolescent school children living in Delhi, India. Lung India. 2021;38(5):408-415.
https://doi.org/10.4103/lungindia.lungindia_955_20
Organización Mundial de la Salud. Contaminación atmosférica y salud infantil: prescribir aire limpio. Resumen. [Internet]. 2018. Disponible en: https://apps.who.int/iris/handle/10665/275548.
Kurtz ML, Astort F, Lezon C, Ferraro SA, Maglione GA, Orona NS et al. Oxidative stress response to air particle pollution in a rat nutritional growth retardation model. J Toxicol Environ Health A. 2018;81(20):1028-1040.
https://doi.org/10.1080/15287394.2018.1519747
Orona NS, Ferraro SA, Astort F, Morales C, Brites F, Boero L et al. Acute exposure to Buenos Aires air particles (UAP-BA) induces local and systemic inflammatory response in middle-aged mice: A time course study. Environ Pollut. 2016;208(Pt A):261-270.
https://doi.org/10.1016/j.envpol.2015.07.020
Marchini T, Magnani ND, Paz ML, Vanasco V, Tasat D, González Maglio DH et al. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash. Toxicol Appl Pharmacol. 2014;274(2):274-82.
https://doi.org/10.1016/j.taap.2013.11.013
Delfosse VC, Tasat DR, Gioffré AK. In vivo short-term exposure to residual oil fly ash impairs pulmonary innate immune response against environmental mycobacterium infection. Environ Toxicol. 2015;30(5):589-96.
https://doi.org/10.1002/tox.21936
Ghio AJ, Silbajoris R, Carson JL, Samet JM. Biologic effects of oil fly ash. Environ Health Perspect. 2002;110(Suppl 1):89-94.
https://doi.org/10.1289/ehp.02110s1189
Ferraro SA, Yakisich JS, Gallo FT, Tasat DR. Simvastatin pretreatment prevents ambient particle-induced lung injury in mice. Inhal Toxicol. 2011;23(14):889-96.
https://doi.org/10.3109/08958378.2011.623195
Leong BK, Coombs JK, Sabaitis CP, Rop DA, Aaron CS. Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats. J Appl Toxicol. 1998;18(2):149-60.
https://doi.org/10.1002/(SICI)1099-1263(199803/04)18:2<149::AID-JAT490>3.0.CO;2-L
28. Southam DS, Dolovich M, O'Byrne PM, Inman MD. Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia. Am J Physiol Lung Cell Mol Physiol. 2002;282(4):L833-9.
https://doi.org/10.1152/ajplung.00173.2001
Magnani ND, Marchini T, Vanasco V, Tasat DR, Alvarez S, Evelson P. Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to residual oil fly ashes. Toxicol Appl Pharmacol. 2013;270(1):31-8.
https://doi.org/10.1016/j.taap.2013.04.002
Tasat DR, de Rey BM. Cytotoxic effect of uranium dioxide on rat alveolar macrophages. Environ Res. 1987;44(1):71-81.
https://doi.org/10.1016/S0013-9351(87)80087-7
McCloy RA, Rogers S, Caldon CE, Lorca T, Castro A, Burgess A. Partial inhibition of Cdk1 in G 2 phase overrides the SAC and decouples mitotic events. Cell Cycle. 2014;13(9):1400-12.
https://doi.org/10.4161/cc.28401
Tasat DR, Lezón CE, Astort F, Pintos PM, Macri EV, Friedman SM et al.mRNA of cytokines in bone marrow and bone biomarkers in response to propranolol in a nutritional growth retardation model. Pharmacol Rep. 2014;66(5):867-73.
https://doi.org/10.1016/j.pharep.2014.05.005
Oberdörster G, Maynard A, Donaldson K, Castranova V, Fitzpatrick J, Ausman K, et al. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol. 2005;2:8.
https://doi.org/10.1186/1743-8977-2-8
Byrne AJ, Mathie SA, Gregory LG, Lloyd CM. Pulmonary macrophages: key players in the innate defence of the airways. Thorax. 2015;70(12):1189-96.
https://doi.org/10.1136/thoraxjnl-2015-207020
Aguayo VM, Menon P. Stop stunting: improving child feeding, women's nutrition and household sanitation in South Asia. Matern Child Nutr. 2016;12 (Suppl 1):3-11.
https://doi.org/10.1111/mcn.12283
Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008;359(1):61-73.
https://doi.org/10.1056/NEJMra0708473
Bharatraj DK, Yathapu SR. Nutrition-pollution interaction: An emerging research area. Indian J Med Res. 2018;148(6):697-704.
https://doi.org/10.4103/ijmr.IJMR_1733_18
Miller CN, Rayalam S. The role of micronutrients in the response to ambient air pollutants: Potential mechanisms and suggestions for research design. J Toxicol Environ Health B Crit Rev. 2017;20(1):38-53.
https://doi.org/10.1080/10937404.2016.1261746
Kordas K, Lönnerdal B, Stoltzfus RJ. Interactions between nutrition and environmental exposures: effects on health outcomes in women and children. J Nutr. 2007;137(12):2794-7.
https://doi.org/10.1093/jn/137.12.2794
Petriello MC, Newsome BJ, Dziubla TD, Hilt JZ, Bhattacharyya D, Hennig B. Modulation of persistent organic pollutant toxicity through nutritional intervention: emerging opportunities in biomedicine and environmental remediation. Sci Total Environ. 2014;491-492:11-6.
https://doi.org/10.1016/j.scitotenv.2014.01.109
Hennig B, Ettinger AS, Jandacek RJ, Koo S, McClain C, Seifried H et al. Using nutrition for intervention and prevention against environmental chemical toxicity and associated diseases. Environ Health Perspect. 2007;115(4):493-5.
https://doi.org/10.1289/ehp.9549
Tao F, Gonzalez-Flecha B, Kobzik L. Reactive oxygen species in pulmonary inflammation by ambient particulates. Free Radic Biol Med. 2003;35(4):327-40.
https://doi.org/10.1016/S0891-5849(03)00280-6
Knaapen AM, Borm PJ, Albrecht C, Schins RP. Inhaled particles and lung cancer. Part A: Mechanisms. Int J Cancer. 2004;109(6):799-809.
https://doi.org/10.1002/ijc.11708
Guan L, Rui W, Bai R, Zhang W, Zhang F, Ding W. Effects of Size-Fractionated Particulate Matter on Cellular Oxidant Radical Generation in Human Bronchial Epithelial BEAS-2B Cells. Int J Environ Res Public Health. 2016;13(5):483.
https://doi.org/10.3390/ijerph13050483
Rui Chen, Hong Yin, Ivan S. Cole, Shirley Shen, Xingfan Zhou, Yuqian Wang et al. Exposure, assessment and health hazards of particulate matter in metal additive manufacturing: A review. Chemosphere. 2020. Volume 259.
https://doi.org/10.1016/j.chemosphere.2020.127452
Ferraro S, Orona N, Villalón L, Saldiva PH, Tasat DR, Berra A. Air particulate matter exacerbates lung response on Sjögren's Syndrome animals. Exp Toxicol Pathol. 2015;67(2):125-31.
https://doi.org/10.1016/j.etp.2014.10.007
Tebay LE, Robertson H, Durant ST, Vitale SR, Penning TM, Dinkova- Kostova AT. Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease. Free Radic. Biol. Med. 2015;88(Pt B):108-146.
https://doi.org/10.1016/j.freeradbiomed.2015.06.021
Vasconcelos AR, Dos Santos NB, Scavone C, Munhoz CD. Nrf2/ARE Pathway Modulation by Dietary Energy Regulation in Neurological Disorders. Front Pharmacol. 2019;10:33.
https://doi.org/10.3389/fphar.2019.00033
Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Lunts A et al. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Health A. 2002;65(20):1531-43.
https://doi.org/10.1080/00984100290071658
Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M et al. Expert Panel on Population and Prevention Science of the American Heart Association. Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation. 2004;109(21):2655-71.
https://doi.org/10.1161/01.CIR.0000128587.30041.C8
Brook RD. Cardiovascular effects of air pollution. Clin Sci (Lond). 2008;115(6):175-87.
https://doi.org/10.1042/CS20070444
Nemmar A, Vanbilloen H, Hoylaerts MF, Hoet PH, Verbruggen A, Nemery B. Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. Am J Respir Crit Care Med. 2001;164(9):1665-8.
https://doi.org/10.1164/ajrccm.164.9.2101036
Lee JH, Suh OK, Lee MG. Pharmacokinetic changes in drugs during protein-calorie malnutrition: correlation between drug metabolism and hepatic microsomal cytochrome P450 isozymes. Arch Pharm Res. 2004;27(7):693-712.
https://doi.org/10.1007/BF02980136
Orona N, Astort F, Maglione GA, Ferraro SA, Martin M, Morales C et al. Hazardous effects of urban air particulate matter acute exposure on lung and extrapulmonary organs in mice. Ecotoxicol. Environ. Saf. 2020;190:110120.
https://doi.org/10.1016/j.ecoenv.2019.110120
Hu H, Wu J, Li Q, Asweto C, Feng L, Yang X et al. Fine particulate matter induces vascular endothelial activation via IL-6 dependent JAK1/STAT3 signaling pathway. Toxicol Res (Camb). 2016;5(3):946-953.
https://doi.org/10.1039/C5TX00351B
Perrella MA, Jain MK, Lee ME. Role of TGF-beta in vascular development and vascular reactivity. Miner Electrolyte Metab. 1998;24(2-3):136- 43.
https://doi.org/10.1159/000057361
Park JH, Kim M, Yim B, Park CY. Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes. Sci Rep. 2021;11(1):8183.
https://doi.org/10.1038/s41598-021-87791-x
Kopf PG, Scott JA, Agbor LN, Boberg JR, Elased KM, Huwe JK et al. Cytochrome P4501A1 is required for vascular dysfunction and hypertension induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci. 2010;117(2):537-46.
https://doi.org/10.1093/toxsci/kfq218
Zhang J, Chen R, Zhang G, Wang Y, Peng J, Hu R, et al. PM2.5 increases mouse blood pressure by activating toll-like receptor 3. Ecotoxicol Environ Saf. 2022;234:113368.