Moderate-intensity Exercise Alleviates Rat’s Systemic Inflammation Induced by Repeated Exposure to Lipopolysaccharide
-
HamidReza Rezaei Moghaddam
,
Toktam Sahranavard
,
Ramin Rezaee
,
Mohammad Hossein Boskabady
,
Zahra Gholamnezhad
Abstract
The protective impacts of physical activity against inflammatory and oxidative stress conditions have been demonstrated. In this study, the impacts of moderate-intensity exercise on oxidative stress-associated factors and proinflammatory cytokines levels as well as the count of white blood cells (WBC) were assessed in a lipopolysaccharide (LPS)-triggered model of inflammation.
Wistar rats were randomized into these groups (8 rats in each): (1) control; (2) LPS; (3) moderate exercise (EX); and (4) moderate exercise + LPS (EX+LPS). Exercise groups were trained for 8 weeks (30 min, 6 days/week) at 15 m/min speed. During the final week of the experiment, 1 mg/kg/day of intraperitoneal LPS was administered for 5 days. On day 56, from the rats’ hearts, peripheral blood was taken for biochemical evaluation.
LPS enhanced serum levels of C-reactive protein (CRP), interleukin (IL)- 1β, tumor necrosis factor-α (TNF-α), metabolites of nitric oxide, and malondialdehyde (MDA), as well as the counts of total WBC, monocytes, neutrophils, and eosinophils, but decreased serum levels of thiol as well as superoxide dismutase (SOD) and catalase (CAT) activity versus the control rats. Moderate exercise reduced the levels of thiol, CAT, and SOD, but increased TNF-α level, and total WBC, neutrophils, eosinophils, and monocytes counts versus the control group. In the EX+LPS group, moderate exercise decreased cell counts and diminished MDA, TNF-α, IL-1β, and CRP levels, while increasing thiol level, CAT, and SOD versus the LPS group.
In our study, exercise preconditioning reduced inflammation induced by LPS by ameliorating inflammatory cytokine levels, WBC counts, and oxidative damage, while improving antioxidant defenses.
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2. Li W, Wu X, Yu J, Ma C, Zhuang P, Zeng J, et al. Magnesium sulfate attenuates lipopolysaccharides-induced acute lung injury in mice. Chin J Physiol. 2019;62(5):203-9.
3. Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736-88.
4. Chatterjee S. Chapter Two - Oxidative Stress, Inflammation, and Disease. In: Dziubla T, Butterfield DA, editors. Oxidative Stress and Biomaterials: Academic Press; 2016. p. 35-58.5.
5. Zhang Y, Fang F, Tang J, Jia L, Feng Y, Xu P, et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. Bmj. 2019;366.
6. Stewart I, Schluter PJ, Shaw GR. Cyanobacterial lipopolysaccharides and human health - a review. Environ Health. 2006;5:7.
7. Cardoso GH, Petry DM, Probst JJ, de Souza LF, Ganguilhet G, Bobinski F, et al. High-intensity exercise prevents disturbances in lung inflammatory cytokines and antioxidant defenses induced by lipopolysaccharide. Inflammation. 2018;41(6):2060-7.
8. Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J. pathol., Clin. res. 2004;202(2):145-56.
9. Wu XX, Huang XL, Chen RR, Li T, Ye HJ, Xie W, et al. Paeoniflorin Prevents Intestinal Barrier Disruption and Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in Caco-2 Cell Monolayers. Inflammation. 2019;42(6):2215-25.
10. Mendez ME, Sebastian A, Murugesh DK, Hum NR, McCool JL, Hsia AW, et al. LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice. J Bone Miner Res. 2020;35(11):2229-41.
11. Yu R, Li Q, Feng Z, Cai L, Xu Q. m6A reader YTHDF2 regulates LPS-induced inflammatory response. Int J Mol Sci. 2019;20(6):1323.
12. Suzuki K, Hayashida H. Effect of exercise intensity on cell-mediated immunity. Sports. 2021;9(1):8.
13. Collao N, Rada I, Francaux M, Deldicque L, Zbinden-Foncea H. Anti-Inflammatory Effect of Exercise Mediated by Toll-Like Receptor Regulation in Innate Immune Cells - A Review. Int Rev Immunol. 2020;39(2):39-52.
14. Nobari H, Cholewa JM, Pérez-Gómez J, Castillo-Rodríguez A. Effects of 14-weeks betaine supplementation on pro-inflammatory cytokines and hematology status in professional youth soccer players during a competition season: a double blind, randomized, placebo-controlled trial. J Int Soc Sports Nutr. 2021;18(1):42.
15. Gholamnezhad Z, Boskabady MH, Hosseini M, Sankian M, Khajavi Rad A. Evaluation of immune response after moderate and overtraining exercise in wistar rat. Iran J Basic Med Sci. 2014;17(1):1-8.
16. Nunes PRP, Martins FM, Souza AP, Carneiro MAS, Orsatti CL, Michelin MA, et al. Effect of high-intensity interval training on body composition and inflammatory markers in obese postmenopausal women: a randomized controlled trial. Menopause. 2019;26(3):256-64.
17. Baygutalp F, Buzdağlı Y, Ozan M, Koz M, Kılıç Baygutalp N, Atasever G. Impacts of different intensities of exercise on inflammation and hypoxia markers in low altitude. BMC Sports Sci Med Rehabil. 2021;13(1):145.
18. Giraldo E, Garcia JJ, Hinchado MD, Ortega E. Exercise intensity-dependent changes in the inflammatory response in sedentary women: role of neuroendocrine parameters in the neutrophil phagocytic process and the pro-/anti-inflammatory cytokine balance. Neuroimmunomodulation. 2009;16(4):237-44.
19. Khoshkhouy F, Farshbaf A, Mahmoudabady M, Gholamnezhad Z. Effects of moderate exercise on lipopolysaccharide-induced inflammatory responses in rat's cardiac tissue. Cytokine. 2021;138:155409.
20. Hou S, Ding H, Lv Q, Yin X, Song J, Landén NX, et al. Therapeutic effect of intravenous infusion of perfluorocarbon emulsion on LPS-induced acute lung injury in rats. PloS one. 2014;9(1):e87826.
21. Saadat S, Beheshti F, Askari VR, Hosseini M, Roshan NM, Boskabady MH. Aminoguanidine affects systemic and lung inflammation induced by lipopolysaccharide in rats. Respir. Res. 2019;20(1):1-13.
22. Amin F, Roohbakhsh A, Memarzia A, Kazerani HR, Boskabady MH. Immediate and late systemic and lung effects of inhaled paraquat in rats. J. Hazard. Mater. 2021;415:125633.
23. Jahangiri Z, Gholamnezhad Z, Hosseini M, Beheshti F, Kasraie N. The effects of moderate exercise and overtraining on learning and memory, hippocampal inflammatory cytokine levels, and brain oxidative stress markers in rats. J Physiol Sci. 2019;69(6):993-1004.
24. Joshi L, Ponnana M, Sivangala R, Chelluri LK, Nallari P, Penmetsa S, et al. Evaluation of TNF-α, IL-10 and IL-6 cytokine production and their correlation with genotype variants amongst tuberculosis patients and their household contacts. PloS one. 2015;10(9):e0137727.
25. Belotto MF, Magdalon J, Rodrigues HG, Vinolo MA, Curi R, Pithon-Curi TC, et al. Moderate exercise improves leucocyte function and decreases inflammation in diabetes. Clin. Exp. Immunol. 2010;162(2):237-43.
26. Alizaei Yousefabadi H, Niyazi A, Alaee S, Fathi M, Mohammad Rahimi GR. Anti-inflammatory effects of exercise on metabolic syndrome patients: a systematic review and meta-analysis. Biol Res Nurs. 2021;23(2):280-92.
27. Gleeson M, McFarlin B, Flynn M. Exercise and Toll-like receptors. Exerc Immunol Rev. 2006;12(1):34-53.
28. Timmerman KL, Flynn MG, Coen PM, Markofski MM, Pence BD. Exercise training‐induced lowering of inflammatory (CD14+ CD16+) monocytes: a role in the anti‐inflammatory influence of exercise? J Leukoc Biol. 2008;84(5):1271-8.
29. Starkie RL, Rolland J, Angus DJ, Anderson MJ, Febbraio MA. Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-alpha levels after prolonged running. Am J Physiol Cell Physiol. 2001;280(4):C769-74.
30. Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol. 1999;515 ( Pt 1)(Pt 1):287-91.
31. Docherty S, Harley R, McAuley JJ, Crowe LAN, Pedret C, Kirwan PD, et al. The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review. BMC Sports Sci Med Rehabil. 2022;14(1):5.
32. Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. Faseb j. 2003;17(8):884-6.
33. Moghaddasi M, Javanmard SH, Reisi P, Tajadini M, Taati M. The effect of regular exercise on antioxidant enzyme activities and lipid peroxidation levels in both hippocampi after occluding one carotid in rat. J Physiol Sci. 2014;64(5):325-32.
34. Naderi R, Mohaddes G, Mohammadi M, Ghaznavi R, Ghyasi R, Vatankhah AM. Voluntary exercise protects heart from oxidative stress in diabetic rats. Adv Pharm Bull. 2015;5(2):231.
35. Li K, Zhu X, Wang Y, Zheng S, Dong G. Effect of aerobic exercise intervention on DDT degradation and oxidative stress in rats. Saudi J Biol Sci. 2017;24(3):664-71.
36. Gholamnezhad Z, Mégarbane B, Rezaee R. Molecular Mechanisms Mediating Adaptation to Exercise. Adv Clin Exp Med. 2020;1228:45-61.
37. Kiyici F, Kishali NF. Acute effect of intense exercises on serum superoxide dismutase, catalase and malondialdehyde levels in soccer players. J Sports Med Phys Fitness. 2012;52(1):107-11.
38. Bloomer R, Davis PG, Consitt L, Wideman L. Plasma protein carbonyl response to increasing exercise duration in aerobically trained men and women. Int J Sports Med. 2007;28(01):21-5.
39. Boskabady M, Khazdair MR, Bargi R, Saadat S, Memarzia A, Mohammadian Roshan N, et al. Thymoquinone Ameliorates Lung Inflammation and Pathological Changes Observed in Lipopolysaccharide-Induced Lung Injury. Evid Based Complement Alternat Med. 2021;2021:6681729.
40. Fodor RS, Georgescu AM, Cioc AD, Grigorescu BL, Cotoi OS, Fodor P, et al. Time- and dose-dependent severity of lung injury in a rat model of sepsis. Rom J Morphol Embryol. 2015;56(4):1329-37.
41. Gholamnezhad Z, Boskabady MH, Hosseini M, Aghaei A, editors. Effect of different loads of exercise and Nigella sativa L. seed extract on serologic and hematologic parameters in rat. Indian J Exp Biol. 2019; 57:21-29.
42. Gleeson M. Immune function in sport and exercise. J Appl Physiol. 2007;103(2):693-9.
43. Neves PRDS, Tenório TRDS, Lins TA, Muniz MTC, Pithon-Curi TC, Botero JP, et al. Acute effects of high-and low-intensity exercise bouts on leukocyte counts. J Exerc Sci Fit 2015;13(1):24-8.
44. Johannsen NM, Swift DL, Johnson WD, Dixit VD, Earnest CP, Blair SN, et al. Effect of different doses of aerobic exercise on total white blood cell (WBC) and WBC subfraction number in postmenopausal women: results from DREW. PLoS One. 2012;7(2):e31319.
45. Michishita R, Shono N, Inoue T, Tsuruta T, Node K. Effect of exercise therapy on monocyte and neutrophil counts in overweight women. Am J Med Sci. 2010;339(2):152-6.
46. Chen J, Zhou R, Feng Y, Cheng L. Molecular mechanisms of exercise contributing to tissue regeneration. Signal Transduct. Target. 2022;7(1):1-24.
2. Li W, Wu X, Yu J, Ma C, Zhuang P, Zeng J, et al. Magnesium sulfate attenuates lipopolysaccharides-induced acute lung injury in mice. Chin J Physiol. 2019;62(5):203-9.
3. Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736-88.
4. Chatterjee S. Chapter Two - Oxidative Stress, Inflammation, and Disease. In: Dziubla T, Butterfield DA, editors. Oxidative Stress and Biomaterials: Academic Press; 2016. p. 35-58.5.
5. Zhang Y, Fang F, Tang J, Jia L, Feng Y, Xu P, et al. Association between vitamin D supplementation and mortality: systematic review and meta-analysis. Bmj. 2019;366.
6. Stewart I, Schluter PJ, Shaw GR. Cyanobacterial lipopolysaccharides and human health - a review. Environ Health. 2006;5:7.
7. Cardoso GH, Petry DM, Probst JJ, de Souza LF, Ganguilhet G, Bobinski F, et al. High-intensity exercise prevents disturbances in lung inflammatory cytokines and antioxidant defenses induced by lipopolysaccharide. Inflammation. 2018;41(6):2060-7.
8. Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J. pathol., Clin. res. 2004;202(2):145-56.
9. Wu XX, Huang XL, Chen RR, Li T, Ye HJ, Xie W, et al. Paeoniflorin Prevents Intestinal Barrier Disruption and Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in Caco-2 Cell Monolayers. Inflammation. 2019;42(6):2215-25.
10. Mendez ME, Sebastian A, Murugesh DK, Hum NR, McCool JL, Hsia AW, et al. LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice. J Bone Miner Res. 2020;35(11):2229-41.
11. Yu R, Li Q, Feng Z, Cai L, Xu Q. m6A reader YTHDF2 regulates LPS-induced inflammatory response. Int J Mol Sci. 2019;20(6):1323.
12. Suzuki K, Hayashida H. Effect of exercise intensity on cell-mediated immunity. Sports. 2021;9(1):8.
13. Collao N, Rada I, Francaux M, Deldicque L, Zbinden-Foncea H. Anti-Inflammatory Effect of Exercise Mediated by Toll-Like Receptor Regulation in Innate Immune Cells - A Review. Int Rev Immunol. 2020;39(2):39-52.
14. Nobari H, Cholewa JM, Pérez-Gómez J, Castillo-Rodríguez A. Effects of 14-weeks betaine supplementation on pro-inflammatory cytokines and hematology status in professional youth soccer players during a competition season: a double blind, randomized, placebo-controlled trial. J Int Soc Sports Nutr. 2021;18(1):42.
15. Gholamnezhad Z, Boskabady MH, Hosseini M, Sankian M, Khajavi Rad A. Evaluation of immune response after moderate and overtraining exercise in wistar rat. Iran J Basic Med Sci. 2014;17(1):1-8.
16. Nunes PRP, Martins FM, Souza AP, Carneiro MAS, Orsatti CL, Michelin MA, et al. Effect of high-intensity interval training on body composition and inflammatory markers in obese postmenopausal women: a randomized controlled trial. Menopause. 2019;26(3):256-64.
17. Baygutalp F, Buzdağlı Y, Ozan M, Koz M, Kılıç Baygutalp N, Atasever G. Impacts of different intensities of exercise on inflammation and hypoxia markers in low altitude. BMC Sports Sci Med Rehabil. 2021;13(1):145.
18. Giraldo E, Garcia JJ, Hinchado MD, Ortega E. Exercise intensity-dependent changes in the inflammatory response in sedentary women: role of neuroendocrine parameters in the neutrophil phagocytic process and the pro-/anti-inflammatory cytokine balance. Neuroimmunomodulation. 2009;16(4):237-44.
19. Khoshkhouy F, Farshbaf A, Mahmoudabady M, Gholamnezhad Z. Effects of moderate exercise on lipopolysaccharide-induced inflammatory responses in rat's cardiac tissue. Cytokine. 2021;138:155409.
20. Hou S, Ding H, Lv Q, Yin X, Song J, Landén NX, et al. Therapeutic effect of intravenous infusion of perfluorocarbon emulsion on LPS-induced acute lung injury in rats. PloS one. 2014;9(1):e87826.
21. Saadat S, Beheshti F, Askari VR, Hosseini M, Roshan NM, Boskabady MH. Aminoguanidine affects systemic and lung inflammation induced by lipopolysaccharide in rats. Respir. Res. 2019;20(1):1-13.
22. Amin F, Roohbakhsh A, Memarzia A, Kazerani HR, Boskabady MH. Immediate and late systemic and lung effects of inhaled paraquat in rats. J. Hazard. Mater. 2021;415:125633.
23. Jahangiri Z, Gholamnezhad Z, Hosseini M, Beheshti F, Kasraie N. The effects of moderate exercise and overtraining on learning and memory, hippocampal inflammatory cytokine levels, and brain oxidative stress markers in rats. J Physiol Sci. 2019;69(6):993-1004.
24. Joshi L, Ponnana M, Sivangala R, Chelluri LK, Nallari P, Penmetsa S, et al. Evaluation of TNF-α, IL-10 and IL-6 cytokine production and their correlation with genotype variants amongst tuberculosis patients and their household contacts. PloS one. 2015;10(9):e0137727.
25. Belotto MF, Magdalon J, Rodrigues HG, Vinolo MA, Curi R, Pithon-Curi TC, et al. Moderate exercise improves leucocyte function and decreases inflammation in diabetes. Clin. Exp. Immunol. 2010;162(2):237-43.
26. Alizaei Yousefabadi H, Niyazi A, Alaee S, Fathi M, Mohammad Rahimi GR. Anti-inflammatory effects of exercise on metabolic syndrome patients: a systematic review and meta-analysis. Biol Res Nurs. 2021;23(2):280-92.
27. Gleeson M, McFarlin B, Flynn M. Exercise and Toll-like receptors. Exerc Immunol Rev. 2006;12(1):34-53.
28. Timmerman KL, Flynn MG, Coen PM, Markofski MM, Pence BD. Exercise training‐induced lowering of inflammatory (CD14+ CD16+) monocytes: a role in the anti‐inflammatory influence of exercise? J Leukoc Biol. 2008;84(5):1271-8.
29. Starkie RL, Rolland J, Angus DJ, Anderson MJ, Febbraio MA. Circulating monocytes are not the source of elevations in plasma IL-6 and TNF-alpha levels after prolonged running. Am J Physiol Cell Physiol. 2001;280(4):C769-74.
30. Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol. 1999;515 ( Pt 1)(Pt 1):287-91.
31. Docherty S, Harley R, McAuley JJ, Crowe LAN, Pedret C, Kirwan PD, et al. The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review. BMC Sports Sci Med Rehabil. 2022;14(1):5.
32. Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. Faseb j. 2003;17(8):884-6.
33. Moghaddasi M, Javanmard SH, Reisi P, Tajadini M, Taati M. The effect of regular exercise on antioxidant enzyme activities and lipid peroxidation levels in both hippocampi after occluding one carotid in rat. J Physiol Sci. 2014;64(5):325-32.
34. Naderi R, Mohaddes G, Mohammadi M, Ghaznavi R, Ghyasi R, Vatankhah AM. Voluntary exercise protects heart from oxidative stress in diabetic rats. Adv Pharm Bull. 2015;5(2):231.
35. Li K, Zhu X, Wang Y, Zheng S, Dong G. Effect of aerobic exercise intervention on DDT degradation and oxidative stress in rats. Saudi J Biol Sci. 2017;24(3):664-71.
36. Gholamnezhad Z, Mégarbane B, Rezaee R. Molecular Mechanisms Mediating Adaptation to Exercise. Adv Clin Exp Med. 2020;1228:45-61.
37. Kiyici F, Kishali NF. Acute effect of intense exercises on serum superoxide dismutase, catalase and malondialdehyde levels in soccer players. J Sports Med Phys Fitness. 2012;52(1):107-11.
38. Bloomer R, Davis PG, Consitt L, Wideman L. Plasma protein carbonyl response to increasing exercise duration in aerobically trained men and women. Int J Sports Med. 2007;28(01):21-5.
39. Boskabady M, Khazdair MR, Bargi R, Saadat S, Memarzia A, Mohammadian Roshan N, et al. Thymoquinone Ameliorates Lung Inflammation and Pathological Changes Observed in Lipopolysaccharide-Induced Lung Injury. Evid Based Complement Alternat Med. 2021;2021:6681729.
40. Fodor RS, Georgescu AM, Cioc AD, Grigorescu BL, Cotoi OS, Fodor P, et al. Time- and dose-dependent severity of lung injury in a rat model of sepsis. Rom J Morphol Embryol. 2015;56(4):1329-37.
41. Gholamnezhad Z, Boskabady MH, Hosseini M, Aghaei A, editors. Effect of different loads of exercise and Nigella sativa L. seed extract on serologic and hematologic parameters in rat. Indian J Exp Biol. 2019; 57:21-29.
42. Gleeson M. Immune function in sport and exercise. J Appl Physiol. 2007;103(2):693-9.
43. Neves PRDS, Tenório TRDS, Lins TA, Muniz MTC, Pithon-Curi TC, Botero JP, et al. Acute effects of high-and low-intensity exercise bouts on leukocyte counts. J Exerc Sci Fit 2015;13(1):24-8.
44. Johannsen NM, Swift DL, Johnson WD, Dixit VD, Earnest CP, Blair SN, et al. Effect of different doses of aerobic exercise on total white blood cell (WBC) and WBC subfraction number in postmenopausal women: results from DREW. PLoS One. 2012;7(2):e31319.
45. Michishita R, Shono N, Inoue T, Tsuruta T, Node K. Effect of exercise therapy on monocyte and neutrophil counts in overweight women. Am J Med Sci. 2010;339(2):152-6.
46. Chen J, Zhou R, Feng Y, Cheng L. Molecular mechanisms of exercise contributing to tissue regeneration. Signal Transduct. Target. 2022;7(1):1-24.
| Files | ||
| Issue | Vol 23 No 3 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i3.15640 | |
| Keywords | ||
| Exercise Inflammation Lipopolysaccharide Oxidative stress White blood cells | ||
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How to Cite
1.
Rezaei Moghaddam H, Sahranavard T, Rezaee R, Boskabady MH, Gholamnezhad Z. Moderate-intensity Exercise Alleviates Rat’s Systemic Inflammation Induced by Repeated Exposure to Lipopolysaccharide. Iran J Allergy Asthma Immunol. 2024;23(3):311-320.
