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تاثیر تمرین هوازی بر مقدار ادم پنجه و سطوح IL-6 ، TNF-α و CC16 سرم موشهای نر تحت مواجهه با آرسنیک | ||
مطالعات کاربردی تندرستی در فیزیولوژی ورزش | ||
دوره 9، شماره 1، فروردین 1401، صفحه 136-150 اصل مقاله (1.38 M) | ||
نوع مقاله: مقاله پژوهشی Released under (CC BY-NC 4.0) license I Open Access I | ||
شناسه دیجیتال (DOI): 10.22049/jahssp.2022.27769.1460 | ||
نویسندگان | ||
امیر داداش زاده؛ رقیه پوزش جدیدی* | ||
گروه فیزیولوژی ورزشی، دانشکده علوم انسانی، دانشگاه آزاد اسلامی واحد تبریز، تبریز، ایران. | ||
چکیده | ||
هدف: قرار گرفتن در معرض آرسنیک از طریق آب آشامیدنی یک مشکل بهداشت عمومی گسترده است که با افزایش خطر پیامدهای متعددی از جمله التهاب همراه است. هدف از این تحقیق، تعیین تاثیر تمرین هوازی بر مقدار ادم پنجه و سطوح IL-6 ، TNF-α و CC16 سرم موشهای نر تحت مواجهه با آرسنیک بود. روش شناسی: در این مطالعه تجربی، تعداد 32 سر موش صحرائی نر به چهار گروه شامل کنترل، آرسنیک، تمرین، و آرسنیک+تمرین تقسیم شدند. آرسنیک به مدت 8 هفته روزانه از طریق آب آشامیدنی با دوز پنج میلیگرم بر هر کیلوگرم وزن بدن به صورت گاواژ خورانده شد. تمرین به مدت هشت هفته با تکرار پنج روز در هفته، با سرعت 10 تا 25 متر در دقیقه، شیب 5 درصد و روزانه به مدت 30-10 دقیقه بر روی تردمیل ویژة جوندگان آزمایشگاهی انجام شد. از روشهای الایزا و حجم سنج پلتیسمومتر به ترتیب برای اندازه گیری سطوح IL-6 ، TNF-α و CC16 سرم و مقدار ادم پنجه پای موش استفاده شد. دادهها با روش تحلیل واریانس یک راهه و آزمون تعقیبی توکی در سطح معنیداری 05/0>p تحلیل شدند. یافتهها: مواجهه با آرسنیک، سبب افزایش سطوح IL-6 ، TNF-α و کاهش CC16 سرم موشهای نر شد (001/0=p برای هر سه متغیر)، اما بر ادم پنجه پای موش تاثیر معنیداری نداشت (8/0=p). مداخله تمرین در مقایسه با گروه کنترل، آرسنیک و آرسنیک+تمرین، افزایش سطوح IL-6 (به ترتیب 001/0=p، 02/0=p، 001/0=p)، TNF-α (به ترتیب 001/0=p، 02/0=p، 03/0=p) و کاهش CC16 سرمی (به ترتیب 03/0=p، 001/0=p، 008/0=p) ناشی از آرسنیک را افزایش داد. با اینحال، تمرین بر ادم پنجه پای موش تاثیر معنیداری نداشت (8/0=p). نتیجهگیری: در حالی که مواجهه با آرسنیک میتواند به افزایش سطوح IL-6، TNF-α و کاهش CC16 سرمی موشها منجر شود، به نظر می رسد که تمرین هوازی این پاسخهای التهابی را برعکس میکند. با این حال، به دلیل برخی محدودیتها و کمبود تحقیقات انسانی، به بررسیهای بیشتر نیاز است. | ||
کلیدواژهها | ||
آرسنیک؛ التهاب؛ ادم؛ CC16؛ تمرین هوازی | ||
مراجع | ||
1. Sanchez TR, Perzanowski M, Graziano JH. Inorganic arsenic and respiratory health, from early life exposure to sex-specific effects: A systematic review. Environmental research. 2016;147:537-55.
2. WHO. Ten Chemicals of Major Public Health Concern. WHO; 2016.
3. WHO. Exposure to cadmium: a major public health concern. World Health Organization (WHO). 2010.
4. Kazemifar AM, Mojdehipanah H, Arami M, Khamesi S. Chronic Arsenic Toxicity from Drinking Well Water in a Rural Area. Iranian Journal of Toxicology. 2017;11(6):33-6. [In Persian]
5. Mosaferi M, Taghipour H, Hassani A, Borghei M, Kamali Z, Ghadirzadeh A. Study of arsenic presence in drinking water sources: a case study. Iranian Journal of Health and Environment. 2008;1(1):19-28. [In Persian]
6. Sun X, He Y, Guo Y, Li S, Zhao H, Wang Y, et al. Arsenic affects inflammatory cytokine expression in Gallus gallus brain tissues. BMC veterinary research. 2017;13(1):1-10.
7. Cheng Y-Y, Chang Y-T, Cheng H-L, Shen K-H, Sung J-M, Guo H-R. Associations between arsenic in drinking water and occurrence of end-stage renal disease with modifications by comorbidities: a nationwide population-based study in Taiwan. Science of The Total Environment. 2018;626:581-91.
8. Pichler G, Grau-Perez M, Tellez-Plaza M, Umans J, Best L, Cole S, et al. Association of arsenic exposure with cardiac geometry and left ventricular function in young adults: evidence from the Strong Heart Family Study. Circulation: Cardiovascular Imaging. 2019;12(5):e009018.
9. Singh MK, Yadav SS, Yadav RS, Chauhan A, Katiyar D, Khattri S. Protective effect of Emblica-officinalis in arsenic induced biochemical alteration and inflammation in mice. Springerplus. 2015;4(1):1-8.
10. Islam LN, Nurun Nabi A, Rahman MM, Zahid MSH. Association of respiratory complications and elevated serum immunoglobulins with drinking water arsenic toxicity in human. Journal of Environmental Science and Health, Part A. 2007;42(12):1807-14.
11. Liu Y, Liang Y, Zheng B, Chu L, Ma D, Wang H, et al. Protective Effects of crocetin on arsenic trioxide-induced hepatic injury: Involvement of suppression in oxidative stress and inflammation through activation of Nrf2 signaling pathway in rats. Drug design, development and therapy. 2020;14:1921.
12. Calatayud M, Gimeno-Alcañiz J, Vélez D, Devesa V. Trivalent arsenic species induce changes in expression and levels of proinflammatory cytokines in intestinal epithelial cells. Toxicology letters. 2014;224(1):40-6.
13. Xu Y, Zhao Y, Xu W, Luo F, Wang B, Li Y, et al. Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells. Toxicology and applied pharmacology. 2013;272(2):542-50.
14. Duan X, Xu G, Li J, Yan N, Li X, Liu X, et al. Arsenic Induces Continuous Inflammation and Regulates Th1/Th2/Th17/Treg Balance in Liver and Kidney In Vivo. Mediators of Inflammation. 2022;2022.
15. Yan N, Xu G, Zhang C, Liu X, Li X, Sun L, et al. Chronic arsenic exposure induces the time-dependent modulation of inflammation and immunosuppression in spleen. Cell & Bioscience. 2020;10(1):1-10.
16. Yu N-H, Pei H, Huang Y-P, Li Y-F. (-)-Epigallocatechin-3-Gallate inhibits arsenic-induced inflammation and apoptosis through suppression of oxidative stress in mice. Cellular Physiology and Biochemistry. 2017;41(5):1788-800.
17. Ramsey KA, Foong RE, Sly PD, Larcombe AN, Zosky GR. Early life arsenic exposure and acute and long-term responses to influenza A infection in mice. Environmental Health Perspectives. 2013;121(10):1187-93.
18. Hunt KM, Srivastava RK, Elmets CA, Athar M. The mechanistic basis of arsenicosis: pathogenesis of skin cancer. Cancer letters. 2014;354(2):211-9.
19. Chirasuthat P, Chirasuthat S, Suchonwanit P. Acute Inflammatory Edema: A Case Report with Histopathological and Immunohistochemical Findings. Journal of Inflammation Research. 2021;14:4877.
20. Zhang P. On arsenic trioxide in the clinical treatment of acute promyelocytic leukemia. Leukemia research reports. 2017;7:29-32.
21. Ahmed S, Akhtar E, Roy A, von Ehrenstein OS, Vahter M, Wagatsuma Y, et al. Arsenic exposure alters lung function and airway inflammation in children: a cohort study in rural Bangladesh. Environment international. 2017;101:108-16.
22. Lakind J, Holgate S, Ownby DR, Mansur A, Helms P, Pyatt D, et al. A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects. Biomarkers. 2007;12(5):445-67.
23. Broeckaert F, Clippe A, Knoops B, Hermans C, Bernard A. Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Annals of the New York Academy of Sciences. 2000;923(1):68-77.
24. Hu T, Sun F, Yu X, Li Q, Zhao L, Hao W, et al. CC16-TNF-α negative feedback loop formed between Clara cells and normal airway epithelial cells protects against diesel exhaust particles exposure-induced inflammation. Aging (Albany NY). 2021;13(15):19442.
25. Kropski JA, Fremont RD, Calfee CS, Ware LB. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest. 2009;135(6):1440-7.
26. Parvez F, Chen Y, Brandt-Rauf PW, Bernard A, Dumont X, Slavkovich V, et al. Nonmalignant respiratory effects of chronic arsenic exposure from drinking water among never-smokers in Bangladesh. Environmental health perspectives. 2008;116(2):190-5.
27. Vieira RdP, Toledo AC, Silva LB, Almeida FM, Damaceno-Rodrigues NR, Caldini EG, et al. Anti-inflammatory effects of aerobic exercise in mice exposed to air pollution. Med Sci Sports Exerc. 2012;44(7):1227-34.
28. Kokkinos P, Myers J. Exercise and physical activity: clinical outcomes and applications. Circulation. 2010;122(16):1637-48.
29. Dimauro I, Paronetto MP, Caporossi D. Exercise, redox homeostasis and the epigenetic landscape. Redox biology. 2020;35:101477.
30. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nature reviews immunology. 2011;11(9):607-15.
31. Allen J, Sun Y, Woods JA. Exercise and the regulation of inflammatory responses. Progress in molecular biology and translational science. 2015;135:337-54.
32. Gianesini S, Tessari M, Bacciglieri P, Malagoni AM, Menegatti E, Occhionorelli S, et al. A specifically designed aquatic exercise protocol to reduce chronic lower limb edema. Phlebology. 2017;32(9):594-600.
33. Menegatti E, Pagani A, Avruscio G, Mucignat M, Gianesini S. The effects of thermal water physical exercise in patients with lower limb chronic venous insufficiency monitored by bioimpedance analysis. Diagnostics. 2020;10(11):889.
34. Farzan SF, Eunus HM, Haque SE, Sarwar G, Hasan AR, Wu F, et al. Arsenic exposure from drinking water and endothelial dysfunction in Bangladeshi adolescents. Environmental Research. 2022:112697.
35. Lee M-Y, Jung B-I, Chung S-M, Bae O-N, Lee J-Y, Park J-D, et al. Arsenic-induced dysfunction in relaxation of blood vessels. Environmental health perspectives. 2003;111(4):513-7.
36. Cai Z, Zhang Y, Zhang Y, Miao X, Li S, Yang H, et al. Use of a mouse model and human umbilical vein endothelial cells to investigate the effect of arsenic exposure on vascular endothelial function and the associated role of calpains. Environmental health perspectives. 2019;127(7):077003.
37. Karczewski J, Śledzińska E, Baturo A, Jończyk I, Maleszko A, Samborski P, et al. Obesity and inflammation. European cytokine network. 2018;29(3):83-94.
38. Grandl G, Wolfrum C, editors. Hemostasis, endothelial stress, inflammation, and the metabolic syndrome. Seminars in immunopathology; 2018: Springer.
39. Wang X, Guo Z, Ding Z, Mehta JL. Inflammation, autophagy, and apoptosis after myocardial infarction. Journal of the American Heart Association. 2018;7(9):e008024.
40. Donges C, Duffield R, Drinkwater E. Effect of Resistance or aerobic exercise training on interleukin-6, C-reactive protein, and body. Med Sci Sports Exerc. 2010;42(2):304-13.
41. Nikniaz L, Ghojazadeh M, Nateghian H, Nikniaz Z, Farhangi MA, Pourmanaf H. The interaction effect of aerobic exercise and vitamin D supplementation on inflammatory factors, anti-inflammatory proteins, and lung function in male smokers: a randomized controlled trial. BMC Sports Science, Medicine and Rehabilitation. 2021;13(1):1-8.
42. Badkoubeh-Hezaveh M, Abedi B, Rahmati-Ahmadabad S. The Effect of Regular Aerobic Exercise Training and Pumpkin Seed Extract on the Heart and Aorta Apoptosis Biomarkers in Arsenic-Intoxicated Rats. Gene, Cell and Tissue. 2021;8(2).
43. Shejawal N, Menon S, Shailajan S. A simple, sensitive and accurate method for rat paw volume measurement and its expediency in preclinical animal studies. Human & experimental toxicology. 2014;33(2):123-9.
44. Escudero-Lourdes C. Toxicity mechanisms of arsenic that are shared with neurodegenerative diseases and cognitive impairment: Role of oxidative stress and inflammatory responses. Neurotoxicology. 2016;53:223-35.
45. Valavanidis A, Vlachogianni T, Fiotakis K. Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles. International journal of environmental research and public health. 2009;6(2):445-62.
46. Wu J, Liu J, Waalkes MP, Cheng M-L, Li L, Li C-X, et al. High dietary fat exacerbates arsenic-induced liver fibrosis in mice. Experimental biology and medicine. 2008;233(3):377-84.
47. Yang C, Wu J, Zhang R, Zhang P, Eckard J, Yusuf R, et al. Caffeic acid phenethyl ester (CAPE) prevents transformation of human cells by arsenite (As) and suppresses growth of As-transformed cells. Toxicology. 2005;213(1-2):81-96.
48. Duan X, Gao S, Li J, Wu L, Zhang Y, Li W, et al. Acute arsenic exposure induces inflammatory responses and CD4+ T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2. Molecular immunology. 2017;81:160-72.
49. Zeng Q, Luo P, Gu J, Liang B, Liu Q, Zhang A. PKC θ-mediated Ca2+/NF-AT signalling pathway may be involved in T-cell immunosuppression in coal-burning arsenic-poisoned population. Environmental toxicology and pharmacology. 2017;55:44-50.
50. Zhao H, Wang Y, Shao Y, Liu J, Wang S, Xing M. Oxidative stress-induced skeletal muscle injury involves in NF-κB/p53-activated immunosuppression and apoptosis response in copper (II) or/and arsenite-exposed chicken. Chemosphere. 2018;210:76-84.
51. Xiaoxu D, Gao S, Li J, Wu L, Zhang Y, Li W. Acute arsenic exposure induces inflammatory responses and CD4+ Tcell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2/Nrf2. Molecular Immunology. 2017;81:160-72.
52. Wu M-M, Chiou H-Y, Ho I-C, Chen C-J, Lee T-C. Gene expression of inflammatory molecules in circulating lymphocytes from arsenic-exposed human subjects. Environmental health perspectives. 2003;111(11):1429-38.
53. Liu J, Liu Y, Goyer RA, Achanzar W, Waalkes MP. Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oral or injected inorganic arsenicals. Toxicological Sciences. 2000;55(2):460-7.
54. Singh N, Kumar D, Lal K, Raisuddin S, Sahu AP. Adverse health effects due to arsenic exposure: modification by dietary supplementation of jaggery in mice. Toxicology and applied pharmacology. 2010;242(3):247-55.
55. Zoccali C, Mallamaci F, Tripepi G. Adipose tissue as a source of inflammatory cytokines in health and disease: focus on end-stage renal disease. Kidney International. 2003;63:S65-S8.
56. Choong TS, Chuah T, Robiah Y, Koay FG, Azni I. Arsenic toxicity, health hazards and removal techniques from water: an overview. Desalination. 2007;217(1-3):139-66.
57. Fallahzadeh RA, Almodaresi SA, Dashti MM, Fattahi A, Sadeghnia M, Eslami H, et al. Zoning of nitrite and nitrate concentration in groundwater using Geografic information system (GIS), case study: drinking water wells in Yazd City. Journal of Geoscience and Environment Protection. 2016;4(3):91-6.
58. Córdova C, Lopes-e-Silva Jr F, Pires AS, Souza VC, Brito CJ, Moraes CF, et al. Long-term resistance training is associated with reduced circulating levels of IL-6, IFN-gamma and TNF-alpha in elderly women. Neuroimmunomodulation. 2011;18(3):165-70.
59. Steensberg A, Fischer CP, Keller C, Møller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. American Journal of Physiology-Endocrinology And Metabolism. 2003;285(2):E433-E7.
60. Fiers W. Tumor necrosis factor characterization at the molecular, cellular and in vivo level. FEBS letters. 1991;285(2):199-212.
61. Matthys P, Mitera T, Heremans H, Van Damme J, Billiau A. Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice. Infection and Immunity. 1995;63(4):1158-64.
62. Mizuhara H, O'Neill E, Seki N, Ogawa T, Kusunoki C, Otsuka K, et al. T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. The Journal of experimental medicine. 1994;179(5):1529-37.
63. Rezaee S, Kahrizi S, Nabavi SM, Hedayati M. VEGF and TNF-α Responses to Acute and Chronic Aerobic Exercise in the Patients with Multiple Sclerosis. Asian J Sports Med. 2020;11:98312. [In Persian]
64. Sloan RP, Shapiro PA, DeMeersman RE, McKinley PS, Tracey KJ, Slavov I, et al. Aerobic exercise attenuates inducible TNF production in humans. Journal of applied physiology. 2007;103(3):1007-11.
65. Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. The Journal of clinical investigation. 2007;117(2):289-96.
66. Tracey KJ. The inflammatory reflex. Nature. 2002;420(6917):853-9.
67. Almuntashiri S, Han Y, Zhu Y, Dutta S, Niazi S, Wang X, et al. CC16 Regulates Inflammation, ROS Generation and Apoptosis in Bronchial Epithelial Cells during Klebsiella pneumoniae Infection. International journal of molecular sciences. 2021;22(21):11459.
68. Halatek T, Sinczuk-Walczak H, Janasik B, Trzcinka-Ochocka M, Winnicka R, Wasowicz W. Health effects and arsenic species in urine of copper smelter workers. Journal of Environmental Science and Health, Part A. 2014;49(7):787-97.
69. Beamer PI, Klimecki WT, Loh M, Van Horne YO, Sugeng AJ, Lothrop N, et al. Association of children’s urinary CC16 levels with arsenic concentrations in multiple environmental media. International journal of environmental research and public health. 2016;13(5):521.
70. Ma Y-N, Wang J, Lee YL, Ren W-H, Lv X-F, He Q-C, et al., editors. Association of urine CC16 and lung function and asthma in Chinese children. Allergy & Asthma Proceedings; 2015.
71. Tufvesson E, Svensson H, Ankerst J, Bjermer L. Increase of club cell (Clara) protein (CC16) in plasma and urine after exercise challenge in asthmatics and healthy controls, and correlations to exhaled breath temperature and exhaled nitric oxide. Respiratory medicine. 2013;107(11):1675-81.
72. Bernard A, Lauwerys R. Low-molecular-weight proteins as markers of organ toxicity with special reference to Clara cell protein. Toxicology letters. 1995;77(1-3):145-51.
73. Johnston CJ, Mango GW, Finkelstein JN, Stripp BR. Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice. American journal of respiratory cell and molecular biology. 1997;17(2):147-55.
74. Moazami M, Abbasian S, AttarzadeHosseini R, Fathi M. The effect of aerobic training on Clara Cell protein 16 (CC16) and cortisol in addicts. Razi Jou of Med Sci. 2015;1(22):132-40. [In Persian]
75. Crosby LM, Waters CM. Epithelial repair mechanisms in the lung. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2010;298(6):L715-L31.
76. Milne S, Li X, Cordero AIH, Yang CX, Cho MH, Beaty TH, et al. Protective effect of club cell secretory protein (CC-16) on COPD risk and progression: a Mendelian randomisation study. Thorax. 2020;75(11):934-43.
77. Alam M, Allinson G, Stagnitti F, Tanaka A, Westbrooke M. Arsenic contamination in Bangladesh groundwater: a major environmental and social disaster. International journal of environmental health research. 2002;12(3):235-53.
78. Arai A, Kitano A, Kurosu T, Yamamoto K, Miki T, Murakami N, et al. Fluid retention during arsenic trioxide treatment in acute promyelocytic leukemia. American journal of hematology. 2005;79(3):247-8.
79. Chen C-M, Chung M-N, Chiu C-Y, Liu S-H, Lan K-C. Inorganic Arsenic Exposure Decreases Muscle Mass and Enhances Denervation-Induced Muscle Atrophy in Mice. Molecules. 2020;25(13):3057.
80. Kim KH, Im H-W, Karmacharya MB, Kim S, Min B-H, Park SR, et al. Low-intensity ultrasound attenuates paw edema formation and decreases vascular permeability induced by carrageenan injection in rats. Journal of Inflammation. 2020;17(1):1-8.
81. Esmaili A, Kamyab M, Fatemikia H, Ahmadzadeh H, Movahed A, Kim E, et al. Experimental Evaluation of Mouse Hind Paw Edema Induced by Iranian Naja oxiana Venom. Archives of Razi Institute. 2021;76(1):139. [In Persian]
82. Vouri SM, Morris EJ, Jiang X, Hofer A-K, Schmidt S, Pepine C, et al. Evaluation of a Beta-blocker–Edema–Loop Diuretic Prescribing Cascade: A Prescription Sequence Symmetry Analysis. American Journal of Hypertension. 2022.
83. Dolan MG, Thornton RM, Fish DR, Mendel FC. Effects of cold water immersion on edema formation after blunt injury to the hind limbs of rats. Journal of Athletic Training. 1997;32(3):233.
84. Jasso-Pineda Y, Díaz-Barriga F, Calderón J, Yáñez L, Carrizales L, Pérez-Maldonado IN. DNA damage and decreased DNA repair in peripheral blood mononuclear cells in individuals exposed to arsenic and lead in a mining site. Biological trace element research. 2012;146(2):141-9.
85. Gamiño-Gutiérrez SP, González-Pérez CI, Gonsebatt ME, Monroy-Fernández MG. Arsenic and lead contamination in urban soils of Villa de la Paz (Mexico) affected by historical mine wastes and its effect on children’s health studied by micronucleated exfoliated cells assay. Environmental Geochemistry and Health. 2013;35(1):37-51.
86. McDermott S, Bao W, Tong X, Cai B, Lawson A, Aelion CM. Are different soil metals near the homes of pregnant women associated with mild and severe intellectual disability in children? Developmental Medicine & Child Neurology. 2014;56(9):888-97.
87. Heck JE, Park AS, Qiu J, Cockburn M, Ritz B. Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood. International journal of hygiene and environmental health. 2014;217(6):662-8.
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