Document Type : Original Article

Authors

1 PhD Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

2 Full Professor, Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.

Abstract

Background and Aim: Exercise is a strong physiological stimulus that can affect the lung apoptosis by in fluencing a number of extracellular and intracellular signaling pathways, directly or indirectly. This study was designed to determine the effects of aerobic exercise training alongside vitamin D supplementation on the expression of apoptosis genes BCL2, BAX, Caspase3 and BCL2/BAX ratio on lung cell apoptosis in male rats exposed to hydrogen peroxide (H2O2). Materials and Methods: Fourty eight male rats were randomly assigned into 6 groups (n=8) including control, hydrogen peroxide (2H), hydrogen peroxide + vitamin D(2HD), hydrogen peroxide + aerobic exercise (2HE), hydrogen peroxide + vitamin D + aerobic exercise (2HDE), and dimethyl sulfoxide (DMSO) groups. For the purpose of inducing apoptosis, 2 mmol/kg of H2O2 was injected three times per week one hour prior to the exercise session. The rats were slaughtered 24 hours following the termination of the exercise sessions and the lung tissue was exposed and stored at -75°C. Then, the RT-PCR method was employed to examine the gene expressions of BAX, BCL2, Caspase3 and BCL2/BAX ratios. It is applied one and two- way analysis of variance and Thuky tests for analysis of data at the significant level of p < 0.05. Results: BCL2 expression in the 2HE group (p=0.004) and 2HD (p=0.006) increased significantly compared to the control group. While the expression of BAX, BCL2/BAX ratio, Caspase3 in the 2HE and 2HD significantly (p < 0.05) was lower than the control group. On the other hand, 2HDE had a decline effect on BAX gene expression (p=0.03) and BCL2/BAX ratio (p=0.04), but did not show significant effect on expression of BCL2 and Caspase3 gene ( p>0.05). Conclusion: It seems that that one course of regular aerobic exercise in addition to consuming vitamin D might is likely to cause significant alteration on the expression of genes involved in apoptosis caused by H2O2 presence can be used as a complementary therapy along with other treatments for apoptosis in lung tissue.

Keywords

Alessio, H. M., & Goldfarb, A. H. (1988). Lipid peroxidation and scavenger enzymes during exercise: adaptive response to training. Journal Applied Physiology, 64(4),1333-1336.
Allon, N., Amir, A., Manisterski, E., Rabinovitz, I., Dachir, S., & Kadar, T. (2009). Inhalation exposure to sulfur mustard in the guinea pig model.clinical, biochemical and histopathological characterization of respiratory injuries. Toxicology and Applied Pharmacology, 241(2), 154-62.
Ames, B. N., & Shigenaga, M. K. (1992). Oxidants are a major contributor to aging. Annals of the New York Academy of Sciences, 663, 85–96.
Barker, T., Martins, T. B., Hill, H. R., Kjeldsberg, C. R., Dixon, B. M., Schneider, E. D., ... & Weaver, L. K. (2013). Circulating pro-inflammatory cytokines are elevated and peak power output correlates with 25-hydroxyvitamin D in vitamin D insufficient adults. European Journal of Applied Physiology, 113(6), 1523-1534.
Calverley, P. M., Anderson, J. A., Celli, B., Ferguson, G. T., Jenkins, C., Jones, P. W., ... & Vestbo, J. (2007). Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. New England Journal of Medicine, 356(8), 775-789.
Cohen, G. M. (1997). Caspases: the executioners of apoptosis. Bio‌chemistry Journal, 326(1), 1-16.
Dawson-Hughes, B., Harris, S. S., Krall, E. A., & Dallal, G. E. (1997). Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. The New England Journal of Medicine, 337(10), 670-6.
Fernandes, T., Magalhães, F. D. C., Carmo, E. C. D., & Oliveira, E. M. D. (2012). Aerobic exercise training inhibits skeletal muscular apoptotic signaling mediated by VEGF-VEGR2 in spontaneously hypertesive rats. Revista Brasileira de Medicina do Esporte, 18(6), 412-418.
Fisher-Wellman, K., & Bloomer, R. J. (2009). Acute exercise and oxidative stress: a 30 year history. Dynamic Medicine, 8(1), 1-25.
Fuchs-Tarlovsky, V. (2012). Role of antioxidants in cancer therapy. Nutrition, 29(1), 15–21.
Ginde, A. A., Mansbach, J. M., & Camargo, C. A. (2009). Vitamin D respiratory infection and asthma. Current Allergy and Asthma Reports, 9(1), 81-87.
Green, D. R., & Reed, J. C. (1998). Mitochondria and Apoptosis. Science, 281, 1309 –1312.
Halder, S. K., Sharan, C., & Al-Hendy, A. (2012). 1, 25-dihydroxyvitamin D3 treatment shrinks uterine leiomyoma tumors in the Eker rat model. Biology of Reproduction, 86(4), 1-10.
Halliwell, B., & Gutteridge, J. M. C. (1999). Free radicals in biology and medicine, 3th Edition. Oxford University Press, Oxford, 1–35.
Hatao, H., Oh-ishi, S., Itoh, M., Leeuwenburgh, C., Ohno, H., Ookawara, T., ... & Matsuoka, T. (2006). Effects of acute exercise on lung antioxidant enzymes in young and old rats. Mechanisms of Ageing and Development, 127(4), 384-390.
Hazel, M., & Clarkson, M. A. (2000). Musculoskeletal assessment: joint range of motion and manual muscle strength. 2th Edition. Lippincott: Williams & Wilkins. 76.
Henson, P. M., & Tuder, R. M. (2008). Apoptosis in the lung: induction, clearance and detection. American Journal of Physiology-Lung Cellular and Molecular Physiology, 294(4), 601–611.
Holick, M. F. (2011). Vitamin D: a d-lightful solution for health. Journal of Investigative Medicine, 59(6), 872–880.
Husain, K., & Hazelrigg, S. R. (2002). Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1587(1), 75-82.
Kalyani, R. R., Corriere, M., & Ferrucci, L. (2014). Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. The Lancet Diabetes & Endocrinology, 2(10), 819-829.
Keren, G., & Epstein, Y. (1980). The effect of high dosage vitamin C intake on aerobic and anaerobic capacity. Journal of Sports Medicine and Physical Fitness, 20(2),145–148.
Koçtürk, S., Kayatekin, B. M., Resmi, H., Açıkgöz, O., Kaynak, C., & Özer, E. (2008). The apoptotic response to strenuous exercise of the gastrocnemius and solues muscle fibers in rats. European Journal of Applied Physiology, 102(5), 515-524.
Li, S. F., Liu, H. X., Zhang, Y. B., Yan, Y. C., & Li ,Y. P. (2010). The protective effects of alpha-ketoacids against oxidative stress on rat spermatozoa in vitro. Asian Journal of Andrology, 12(2), 247-256.
Lohar, D. P., Haridas, S., Gantt, J. S., & VandenBosch, K. A. (2007). A transient decrease in reactive oxygen species in roots leads to root hair deformation in the legume-rhizobia symbiosis. New Phytologist, 173(1), 39-49.
Looker, A. C. (2007). Do body fat and exercise modulate vitamin D status?. Nutrition Reviews, 65(8), 124-6.
Ma, Y., Trump, D. L., & Johnson, C. S. (2010). Vitamin D in combination cancer treatment. Journal Cancer, 1, 101–107.
Magi, B., Bargagli, E., Bini, L., & Rottoli, P. (2006). Proteome analysis of bronchoalveolar lavage in lung diseases. Proteomics and System Biology, 6(23), 6354-69.
McMillan, E. M., Graham, D. A., Rush, J. W., & Quadrilatero, J. (2012). Decreased DNA fragmentation and apoptotic signaling in soleus muscle of hypertensive rats following 6 weeks of treadmill training. Journal of Applied Physiology, 113(7), 1048-1057.
Mignotte, B., & Vayssiere, J. L. (1998). Mitochondria and apoptosis. European Journal of Biochemistry, 252(1), 1-15.
Modir, M., Daryanoosh, F., Firouzmand, H., Jaffari, H., & Khanzade, M. (2014). Effect of short and medium periods of high intensities aerobic training on serum level of superoxide dismutase and Catalase enzymes in rats. Journal of Gorgan University of Medical Sciences, 16(3), 24-30. [Persian]
Nanda, A. K., Andrio, E., Marin, D., Pauly, N., & Dunand, C. (2010). Reactive oxygen species during plant-microorganism early interactions. Journal of Integrative Plant Biology, 52(2), 195-204.
Phaneuf, S., & Leewenburgh, C. (2001). Apoptosis and exercise. Medicine & Science in Sports & Exercice, 33(3), 393-6.
Pike, J. W., Zella, L. A., Meyer, M. B., Fretz, J. A., & Kim, S. (2007). Molecular actions of 1, 25-dihydroxyvitamin D3 on genes involved in calcium homeostasis. Journal of Bone and Mineral Research, 22(2), 16–19.
Plant, D. R., Gregorevic, P., Warmington, S. A., Williams, D. A., & Lynch, G. S. (2003). Endurance training adaptations modulate the redox–force relationship of rat isolated slow‐twitch skeletal muscles. Clinical and Experimental Pharmacology and Physiology, 30(1‐2), 77-81.
Podhorska-Okolow, M., Dziegiel, P., Gomulkiewicz, A., Kisiela, D., Dolinska-Krajewska, B., Jethon, Z., … & Zabel, M. (2006). Exercise-induced apoptosis in rat kidney is mediated by both angiotensin II AT1 and AT2 receptors. Journal of Histology & Histopathology: Cellular and Molecular Biology, 21(5), 459-66.
Polidoro, L., Properzi, G., Marampon, F., Gravina, G. L., Festuccia, C., Di Cesare, E., ... & Ferri, C. L. A. U. D. I. O. (2013). Vitamin D protects human endothelial cells from H 2 O 2 oxidant injury through the Mek/Erk-Sirt1 axis activation. Journal of Cardiovascular Translational Research, 6(2), 221-231.
Quadrilatero, J., Alway, S. E., & Dupont-Versteegden, E. E. (2011). Skeletal muscle apoptotic response to physical activity: potential mechanisms for protection. Applied Physiology, Nutrition, and Metabolism, 36(5), 608-617.
Quadrilatero, J., Always, S. E., & Dupont-Versteegden, E. E. (2011). Skeletal muscle apoptotic response to physical activity: potential mechanisms for protection. Applied Physiology, Nutrition and Metabolism, 36(5), 608-17.
Sakurai, R., Shin, E., Fonseca, S., Sakurai, T., Litonjua, A. A., Weiss, S. T., ... & Rehan, V. K. (2009). 1α, 25 (OH) 2D3 and its 3-epimer promote rat lung alveolar epithelial-mesenchymal interactions and inhibit lipofibroblast apoptosis. American Journal of Physiology-Lung Cellular and Molecular Physiology, 297(3), L496-L505.
Sergeev, I. N. (2014). Vitamin D-mediated apoptosis in cancer and obesity. Hormone Molecular Biology and Clinical Investigation, 20(2), 43–49.
Sies, H., & Sies, H. (1985). Oxidative stress: introductory remarks Oxidative Stress. New York Academic Journal, 5, 1–7.
Simon-Schnass, I., & Pabst, H. (1988). Influence of vitamin E on physical performance. International Journal for Vitamin and Nutrition Research, 58(1), 49–54.
Slominski, A. T., Brożyna, A. A., Zmijewski, M. A., Jóźwicki, W., Jetten, A. M., Mason, R. S., ... & Elmets, C. A. (2017). Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management. Laboratory Investigation, 97(6), 706-724.
Sun, Y., Cui, D., Zhang, Z., Zhang, T., Shi, J., Jin, H., ... & Ding, S. (2016). Attenuated oxidative stress following acute exhaustive swimming exercise was accompanied with modified gene expression profiles of apoptosis in the skeletal muscle of mice. Oxidative Medicine and Cellular Longevity, 2016, 1-8.
Weiner, P., Berar-Yanay, N., Davidovich, A., Magadle, R., & Weiner, M. (2000). Specific inspiratory muscle training in patients with mild asthma with high consumption of inhaled β2-Agonists agonists. Chest, 117(3), 722-727.
Wong, M. L., & Medrana, J. F. (2005). Real-time PCR for mRNA quantitation. Bio Techniques, 39(1), 75-85.
Zhang, L., Lin, J., Guo, J., Sun W., & Pan, L. (2013). Effects of 1, 25-(OH)2D3 on airway remodeling and airway epithelial cell apoptosis in a murine model of asthma, Zhonghua Yi Xue Za Zhi, 95(48), 3945-9.