Analysis Of The Physical Activity Effects And Measurement Of Pro-inflammatory Cytokines In Irradiated Lungs In Rats [análise Dos Efeitos Da Atividade Física E Mensuração De Citocinas Pró-inflamatórias Em Pulmões Irradiados Em Ratos]

PURPOSE: To study if the pre-radiotherapy physical activity has radio-protective elements, by measuring the radio-induced activation of pro-inflammatory cytokines as interleukin-6 (il-6), transforming growth factor -β (tgf -β), tumor necrosis factor -α (tnf-α) and protein beta kinase β (ikkβ), through western blotting analysis. METHODS: A randomized study with 28 Wistar hannover rats, males, with a mean age of 90 days and weighing about 200 grams. The animals were divided into three groups: (GI, GII and GIII). GIII group were submitted to swimming for eight weeks (zero load, three times a week, about 30 minutes). Then, the groups (except the control group) were submitted to irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All animals were sacrificed by overdose of pentobarbital, according to the time for analysis of cytokines, and then a fragment of the lower lobe of the right lung went to western blotting analysis. RESULTS: The cytokines IKK β, TNF-α and IL-6 induced by radiation in the lung were lower in the exercised animals. However, exercise did not alter the radiation-induced increase in tgf-β. CONCLUSION: The results show a lower response in relation to inflammatory cytokines in the group that practiced the exercise pre-radiotherapy, showing that exercise can protect tissues from tissue damage due to irradiation.273223230Liao, Z., Cox, J.D., Komaki, R., Radiochemotherapy of esofaphageal cancer (2007) J Thorac Oncol, 2 (6), pp. 553-568D'amico, T.A., Outcomes after surgery for esophageal cancer (2007) Gastrointest Cancer Res, 1 (5), pp. 188-196Tercioti Jr., V., Lopes, L.R., Coelho, N.J.D., Carvalheira, J.B., Andreollo, N.A., Local effectiveness and complications of neoadjuvant therapy in esophageal squamous cell carcinoma: Radiotherapy versus chemoradiotherapy (2011) Rev Col Bras Cir, 38 (4), pp. 227-234Miyata, H., Yamasaki, M., Takiguchi, S., Nakajima, K., Fujiwara, Y., Nishida, T., Mori, M., Doki, Y., Salvage esophagectomy after definitive chemoradiotherapy for thoracic esophageal cancer (2009) J Surg Oncol, 100, pp. 442-446Asakura, H., Hashimoto, T., Zenda, S., Harada, H., Hirakawa, K., Mizumoto, M., Furutani, K., Nishimura, T., Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer (2010) Radiother Oncol, 95, pp. 240-244Yu, H.M., Liu, Y.F., Cheng, Y.F., Hu, L.K., Hou, M., Effects of rhubarb extract on radiation induced lung toxicity via decreasing transforming growth factor-beta-1 and interleukin-6 in lung cancer patients treated with radiotherapy (2008) Lung Cancer, 59, pp. 219-226Sakai, M., Iwakawa, M., Iwakura, Y., Ohta, T., Tsujii, H., Imai, T., CD44 and bak expression in IL-6 or TNF-alpha gene knockout mice after whole lung irradiation (2008) J Radiat Res, 49, pp. 409-416Novakova-Jiresova, A., Luijk, P.V., Goor, H.V., Kampinga, H.H., Coppes, R.P., Pulmonary radiation injury: Identification of risk factors associated with regional hypersensitivity (2005) Cancer Res, 65, pp. 3568-3576Bao, P., Gao, W., Li, S., Zhang, L., Qu, S., Wu, C., Qi, H., Effect of pretreatment with high-dose ulinastatin in preventing radiation-induced pulmonary injury in rats (2009) Eur J Pharmacol, 603, pp. 114-119Schmid, J.A., Birbach, A., IkB kinase β (Ikkβ/Ikk2/IkBkB)- a key molecule in signaling to the transcription factor NF-kB (2008) Cytokine Growth Factor Rev, 19, pp. 157-165Mussi, R.K., Camargo, E.A., Ferreira, T., de Moraes, C., Delbin, M.A., Toro, I.F., Brancher, S., Antunes, E., Exercise training reduces pulmonary ischaemia-reperfusion-induced inflammatory responses (2008) Eur Respir J, 31 (3), pp. 645-649Gannon, G.A., Rhind, S.G., Suzui, M., Shek, P.N., Shephard, R.J., Circulating levels of peripheral blood leucocytes and cytokines following competitive cycling (1997) Can J Appl Physiol, 22, pp. 133-147Nieman, D.C., Special feature for the Olympics: Exercise effects on systemic immunity (2000) Immunol Cell Biol, 78, pp. 496-501Triboulet, J.P., Mariette, C., Esophageal squamous cell carcinoma stage III: State of surgery after radiochemotherapy (2006) Cancer Radiother, 10, pp. 456-461Hermann, R.M., Horstmann, O., Haller, F., Perske, C., Christiansen, H., Hille, A., Schimidberger, H., Füzesi, L., Histomorphological tumor regression grading esophageal carcinoma after neoadjuvante radiochemotherapy: With score to use? (2006) Dis Esophagus, 5, pp. 329-334Cagol, M., Ruol, A., Sileni, V.C., de Salvo, G.L., Corti, L., Alfieri, R., Innocente, R., Ancona, E., Multinodal treatment in locally advanced esophageal cancer: A multicenter phase II study with neoadjuvant oxaliplatin, 5-fluorouracil, leucovorin and neoadjuvante radiotherapy: Prelimirary results (2006) Chir Ital, 4, pp. 433-439Rübe, C.E., Wilfert, F., Uthe, D., Schmid, K.W., Knoop, R., Willich, N., Schuck, A., Rübe, C., Modulation of radiation-induced tumor necrosis factor α (TNF-α) expression in the lung tissue by pentoxifyline (2002) Radiother Oncol, 64, pp. 177-187Arnold, R., Humbert, B., Werchau, H., Gallati, H., Königg, W., Interleukin-8, interleukin-6, and soluble tumor necrosis factor receptor type I release from a human pulmonary epithelial cell line (A549) exposed to respiratory syncytial virus (1994) Immunology, 82, pp. 126-133Chen, Y., Rubin, P., Williams, J., Hernady, E., Smudzin, T., Okunieff, P., (2001) Int J Radiat Oncol Biol Phys, 49 (3), pp. 641-648Sriwijitkamol, A., Coletta, D.K., Wajcberg, E., Balbontin, G.B., Reyna, S.M., Barrientes, J., Eagan, P.A., Musi, N., Effect of acute exercise on AMPK signiling in skeletal muscle of subjects with type 2 diabetes: A time-course and dose-response study (2007) Diabetes, 56 (3), pp. 836-848Anscher, M.S., Peters, W.P., Reisenbichler, H., Petros, W.P., Jirtle, R.L., Transforming growth factor beta as predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer (1993) N Engl J Med, 328, pp. 1592-1598Fu, X.L., Huang, H., Bentel, G., Clough, R., Jirtle, R.L., Kong, F.M., Marks, L.B., Anscher, M.S., Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V30 and transforming growth factor β (2001) Int J Radiat Oncol Biol Phys, 50 (4), pp. 899-908Mattos, M.D., Kimura, E.T., Silva, M.R.R., Egami, M.I., Segreto, R.A., Segreto, H.R.C., Ativação da proteína TGFβ1 latente em pulmão irradiado in vivo (2002) Rev Assoc Med Bras, 48 (4), pp. 329-334Lixuan, Z., Jingcheng, D., Wenqin, Y., Jianhua, H., Baojun, L., Xiaotao, F., Baicalin attenuates inflammation by inhibiting NF-kappaβ activation in cigarette smoke induced inflammatory models (2010) Pulm Pharmacol Ther, 23 (5), pp. 411-419Colbert, L.H., Davis, J.M., Essig, D.A., Ghaffar, A., Mayer, E.P., Tissue expression and plasma concentrations of TNF-α, IL-1β, and IL-6 following treadmill exercise in mice (2001) Int J Sports Med, 22, pp. 261-267Ostrowski, K., Rohde, T., Zacho, M., Asp, S., Pedersen, B.K., Evidence that interleukin-6 is produced in human skeletal muscle during prolonged running (1998) J Physiol, 508, pp. 949-953Ullum, H., Haahr, P.M., Diamant, M., Palmo, J., Halkjaer-Kristensen, J., Pedersen, B.K., Bicycle exercise enhances plasma IL-6 but does not change IL-1α, IL-1β, IL-6 or TNFα pre-mRNA in BMNC (1994) J Appl Physiol, 77, pp. 93-97Oliveira, A.G., Carvalho, B.M., Tobar, N., Ropelle, E.R., Pauli, J.R., Bagarolli, R.A., Guadagnini, D., Saad, M.J., Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats (2011) Diabetes, 60, pp. 784-796Lira, F.S., Rosa, J.C., Pimentel, G.D., Tarini, V.A.F., Arida, R.M., Faloppa, F., Alves, E.S., Santos, R.V., Inflammation and adipose tissue: Effects of progressive load training in rats (2010) Lipids Health Dis, 9, p. 109Ropelle, E.R., Flores, M.B., Cintra, D.E., Rocha, G.Z., Pauli, J.R., Morari, J., de Souza, C.T., Carvalheira, J.B., IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition (2010) PLoS Biol, 8 (8), pp. e1000465Chen, L., Wang, T., Wang, X., Sun, B.B., Li, J.Q., Liu, D.S., Zhang, S.F., Wen, F.Q., Blockade of advanced glycation end product formation attenuates bleomycin-induced pulmonary fibrosis in rats (2009) Respir Res, 10, p. 55Kim, J.Y., Kim, Y.S., Kim, Y.K., Park, H.J., Kim, S.J., Kang, J.H., Wang, Y.P., Yoon, S.C., TGF-β1 dynamics during radiation therapy and its correlation to symptomatic radiation pneumonitis in lung cancer patients (2009) Radiat Oncol, 4, p. 59Moon, C., Lee, Y.J., Park, H.J., Chong, Y.H., Kang, J.L., N-acetylcysteine inhibits RhoA and promotes apoptotic cell clearance during intense lung inflammation (2010) Am J Respir Crit Care Med, 181, pp. 374-387Morita, M., Yoshida, R., Ikeda, K., Egashira, A., Oki, E., Sadanaga, N., Kakeji, Y., Maehara, Y., Acute lung injury following an esophagectomy for esophageal cancer, with special reference to the clinical factors and cytokine levels of peripheral blood and pleural drainage fluid (2008) Dis Esophagus, 21 (1), pp. 30-36Sakamoto, K., Arakawa, H., Mita, S., Ishiko, T., Ikei, S., Egami, H., Hisano, S., Ogawa, M., Elevation of circulating interleukin-6 after surgery: Factors influencing serum level (1994) Cytokine, 6, pp. 181-186Adams, E.J., Warrington, A.P., A comparison between cobalt and linear accelerator-based treatment plans for conformal and intensity-modulated radiotherapy (2008) Br J Radiol, 81, pp. 304-310Jin, H., Tucker, S.L., Liu, H.H., Wei, X., Yom, S.S., Wang, S., Komaki, R., Liao, Z., Dose-volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy (2009) Radiother Oncol, 91, pp. 427-432Werner-Wasik, M., Yorke, E., Deasy, J., Nam, J., Marks, L.B., Radiation dose-volume effects in the esophagus (2010) Int J Radiat Oncol Biol Phys, 76 (3), pp. S86-S93Kocak, Z., Borst, G.R., Zeng, J., Zhou, S., Hollis, R., Zhang, J., Evans, E.S., Marks, L.B., Prospective assessment of dosimetric/physiologic-based models for predicting radiation pneumonitis (2007) Int J Radiat Oncol Biol Phys, 67 (1), pp. 178-186Yorke, E.D., Jackson, A., Rosenzweig, K.E., Braban, L., Leibel, S.A., Ling, C.C., Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study (2005) Int J Radiat Oncol Biol Phys, 63 (3), pp. 672-682Hope, A.J., Lindsay, P.E., El-Naga, I., Alaly, J.R., Vicic, M., Bradley, J.D., Deasy, G.O., Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial parameters (2006) Int J Radiat Oncol Biol Phys, 65 (1), pp. 112-124Tsujino, K., Hirota, S., Endo, M., Obayashi, K., Kotani, Y., Satouchi, M., Kado, T., Takada, Y., Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer (2003) Int J Radiat Oncol Biol Phys, 55 (1), pp. 110-115Fay, M., Tan, A., Fisher, R., Mac, M.M., Wirth, A., Ball, D., Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy (2005) Int J Radiat Oncol Biol Phys, 61 (5), pp. 1355-1363Szabo, S., Ghosh, S.N., Fish, B.L., Bodiga, S., Tomic, R., Kumar, G., Morrow, N.V., Medhora, M., Cellular inflammatory infiltrate in pneumonitis induced by a single moderate dose of thoracic versus radiation in rats (2010) Radiat Res, 173 (4), pp. 545-556Dähn, D., Martell, J., Vorwerk, H., Hess, C.F., Becker, H., Jung, K., Hilgers, R., Christiansen, H., Influence of irradiated lung volumes on perioperative morbidity and mortality in patients after neoadjuvante radiochemotherapy for esophageal cancer (2010) Int J Radiat Oncol Biol Phys, 77 (1), pp. 44-52Ysayama, L., Lopes, L.R., Silva, A.M.O., Andreollo, N.A., The influence of the respiratory muscular training in the recovery of esophagectomies (2008) ABCD Arq Bras Cir Dig, 21 (2), pp. 61-64Nakamura, M., Iwahashi, M., Nakamori, M., Ishida, K., Naka, T., Iida, T., Katsuda, M., Yamaue, H., An analysis of the factors contributing to a reduction in the incidence of pulmonary complications following an esophagectomy for esophageal cancer (2008) Langenbecks Arch Surg, 393, pp. 127-13