Skip to main content
SpringerLink
Log in

Experimental lung injury promotes alterations in energy metabolism and respiratory mechanics in the lungs of rats: prevention by exercise

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

In the present study we investigated the effects of lung injury on energy metabolism (succinate dehydrogenase, complex II, cytochrome c oxidase, and ATP levels), respiratory mechanics (dynamic and static compliance, elastance and respiratory system resistance) in the lungs of rats, as well as on phospholipids in bronchoalveolar lavage fluid. The protective effect of physical exercise on the alterations caused by lung injury, including lung edema was also evaluated. Wistar rats were submitted to 2 months of physical exercise. After this period the lung injury was induced by intratracheal instillation of lipopolysaccharide. Adult Wistar rats were submitted to 2 months of physical exercise and after this period the lung injury was induced by intratracheal instillation of lipopolysaccharide in dose 100 μg/100 g body weight. The sham group received isotonic saline instillation. Twelve hours after the injury was performed the respiratory mechanical and after the rats were decapitated and samples were collected. The rats subjected to lung injury presented a decrease in activities of the enzymes of the electron transport chain and ATP levels in lung, as well as the formation of pulmonary edema. A decreased lung dynamic and static compliance, as well as an increase in respiratory system resistance, and a decrease in phospholipids content were observed. Physical exercise was able to totally prevent the decrease in succinate dehydrogenase and complex II activities and the formation of pulmonary edema. It also partially prevented the increase in respiratory system resistance, but did not prevent the decrease in dynamic and static compliance, as well as in phospholipids content. These findings suggest that the mitochondrial dysfunction may be one of the important contributors to lung damage and that physical exercise may be beneficial in this pathology, although it did not prevent all changes present in lung injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R (1994) The American–European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149(1):818–824

    Article  CAS  PubMed  Google Scholar 

  2. Hagiwara S, Iwasaka H, Togo K, Noguchi T (2008) A neutrophil elastase inhibitor, sivelestat, reduces lung injury following endotoxin-induced shock in rats by inhibiting HMGB1. Inflammation 31(4):227–234

    Article  CAS  PubMed  Google Scholar 

  3. da Cunha AA, Nunes FB, Lunardelli A, Pauli V, Amaral RH, de Oliveira LM, Saciura VC, da Silva GL, Pires MG, Donadio MV, Melo DA, Dal-Pizzol F, Moreira JC, Behr GA, Reichel CL, Rosa JL, de Oliveira JR (2011) Treatment with N-methyl-d-aspartate receptor antagonist (MK-801) protects against oxidative stress in lipopolysaccharide-induced acute lung injury in the rat. Int Immunopharmacol 11:706–711

    Article  PubMed  Google Scholar 

  4. Windsor AC, Mullen PG, Fowler AA (1993) Acute lung injury: what have we learned from animal models? Am J Med Sci 306(2):111–116

    Article  CAS  PubMed  Google Scholar 

  5. Sutcliffe AJ (1994) The future of ARDS. Injury 25(9):587–593

    Article  CAS  PubMed  Google Scholar 

  6. Ware LB, Matthay MA (2000) The acute respiratory distress syndrome. N Engl J Med 342(18):1334–1349

    Article  CAS  PubMed  Google Scholar 

  7. Saikumar P, Dong Z, Weinberg JM, Venkatachalam MA (1998) Mechanisms of cell death in hypoxia/reoxygenation injury. Oncogene 17(25):3341–3349

    Article  PubMed  Google Scholar 

  8. Schild L, Reinheckel T, Wiswedel I, Augustin W (1997) Short-term impairment of energy production in isolated rat liver mitochondria by hypoxia/reoxygenation: involvement of oxidative protein modification. Biochem J 328(Pt 1):205–210

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Brooks KJ, Hargreaves IP, Bates TE (2008) Protection of respiratory chain enzymes from ischaemic damage in adult rat brain slices. Neurochem Res 33(9):1711–1716

    Article  CAS  PubMed  Google Scholar 

  10. Sommer SP, Sommer S, Sinha B, Wiedemann J, Otto C, Aleksic I, Schimmer C, Leyh RG (2011) Ischemia–reperfusion injury-induced pulmonary mitochondrial damage. J Heart Lung Transplant 30(7):811–818

    Article  PubMed  Google Scholar 

  11. Mabalirajan U, Dinda AK, Kumar S, Roshan R, Gupta P, Sharma SK, Ghosh B (2008) Mitochondrial structural changes and dysfunction are associated with experimental allergic asthma. J Immunol 181(5):3540–3548

    CAS  PubMed  Google Scholar 

  12. Reddy PH (2008) Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular Med 10(4):291–315

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Beal MF (2005) Mitochondria take center stage in aging and neurodegeneration. Ann Neurol 58(4):495–505

    Article  CAS  PubMed  Google Scholar 

  14. Maurer I, Zierz S, Moller HJ (2000) A selective defect of cytochrome c oxidase is present in brain of Alzheimer’s disease patients. Neurobiol Aging 21(3):455–462

    Article  CAS  PubMed  Google Scholar 

  15. Trigulova VS (1978) Cytochrome oxidase activity in diabetes mellitus. Probl Endokrinol (Mosk) 24(1):14–16

    CAS  Google Scholar 

  16. Raby BA, Klanderman B, Murphy A, Mazza S, Camargo CA Jr, Silverman EK, Weiss ST (2007) A common mitochondrial haplogroup is associated with elevated total serum IgE levels. J Allergy Clin Immunol 120(2):351–358

    Article  CAS  PubMed  Google Scholar 

  17. Pinho RA, Chiesa D, Mezzomo KM, Andrades ME, Bonatto F, Gelain D, Dal Pizzol F, Knorst MM, Moreira JC (2007) Oxidative stress in chronic obstructive pulmonary disease patients submitted to a rehabilitation program. Respir Med 101(8):1830–1835

    Article  CAS  PubMed  Google Scholar 

  18. Blair SN, Cheng Y, Holder JS (2001) Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc 33(6 Suppl):S379–S399 discussion S419–420

    Article  CAS  PubMed  Google Scholar 

  19. Lenz TL, Monaghan MS (2008) Lifestyle modifications for patients with hypertension. J Am Pharm Assoc (2003) 48(4):e92–e99 quiz e100–102

    Article  Google Scholar 

  20. Vieira RP, de Andrade VF, Duarte AC, Dos Santos AB, Mauad T, Martins MA, Dolhnikoff M, Carvalho CR (2008) Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling. Am J Physiol Lung Cell Mol Physiol 295(4):L670–L679

    Article  CAS  PubMed  Google Scholar 

  21. Gill JM, Cooper AR (2008) Physical activity and prevention of type 2 diabetes mellitus. Sports Med 38(10):807–824

    Article  PubMed  Google Scholar 

  22. Blaha MJ, Bansal S, Rouf R, Golden SH, Blumenthal RS, Defilippis AP (2008) A practical “ABCDE” approach to the metabolic syndrome. Mayo Clin Proc 83(8):932–941

    PubMed  Google Scholar 

  23. Servais S, Couturier K, Koubi H, Rouanet JL, Desplanches D, Sornay-Mayet MH, Sempore B, Lavoie JM, Favier R (2003) Effect of voluntary exercise on H2O2 release by subsarcolemmal and intermyofibrillar mitochondria. Free Radic Biol Med 35(1):24–32

    Article  CAS  PubMed  Google Scholar 

  24. Nakamoto H, Kaneko T, Tahara S, Hayashi E, Naito H, Radak Z, Goto S (2007) Regular exercise reduces 8-oxodG in the nuclear and mitochondrial DNA and modulates the DNA repair activity in the liver of old rats. Exp Gerontol 42(4):287–295

    Article  CAS  PubMed  Google Scholar 

  25. Pinho RA, Silveira PCL, Piazza M, Tuon T, Slva GA, Dal-Pizzol F, Moreira JCF (2006) Exercício físico regular diminui o estresse oxidativo pulmonar em ratos após exposição aguda ao carvão mineral. Rev Bras Med Esporte 2(2):81–84

    Google Scholar 

  26. da Cunha MJ, da Cunha AA, Ferreira AGK, Baladão ME, Savio LEB, Reichel CL, Kessler A, Netto CAWATS (2013) Effect of exercise on oxidative stress induced by experimental lung injury. Life Sci 92(3):218–227

    Article  CAS  PubMed  Google Scholar 

  27. Cechetti F, Rhod A, Simao F, Santin K, Salbego C, Netto CA, Siqueira IR (2007) Effect of treadmill exercise on cell damage in rat hippocampal slices submitted to oxygen and glucose deprivation. Brain Res 1157:121–125

    Article  CAS  PubMed  Google Scholar 

  28. Ben J, Soares FM, Cechetti F, Vuaden FC, Bonan CD, Netto CA, Wyse AT (2009) Exercise effects on activities of Na(+), K(+)-ATPase, acetylcholinesterase and adenine nucleotides hydrolysis in ovariectomized rats. Brain Res 1302:248–255

    Article  CAS  PubMed  Google Scholar 

  29. Brooks GA, White TP (1978) Determination of metabolic and heart rate responses of rats to treadmill exercise. J Appl Physiol 45(6):1009–1015

    CAS  PubMed  Google Scholar 

  30. Ritter C, da Cunha AA, Echer IC, Andrades M, Reinke A, Lucchiari N, Rocha J, Streck EL, Menna-Barreto S, Moreira JC, Dal-Pizzol F (2006) Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide-induced acute lung injury in the rat. Crit Care Med 34(2):471–477

    Article  CAS  PubMed  Google Scholar 

  31. Asti C, Ruggieri V, Porzio S, Chiusaroli R, Melillo G, Caselli GF (2000) Lipopolysaccharide-induced lung injury in mice. I. Concomitant evaluation of inflammatory cells and haemorrhagic lung damage. Pulm Pharmacol Ther 13(2):61–69

    Article  CAS  PubMed  Google Scholar 

  32. Fischer JC, Ruitenbeek W, Berden JA, Trijbels JM, Veerkamp JH, Stadhouders AM, Sengers RC, Janssen AJ (1985) Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clin Chim Acta 153(1):23–36

    Article  CAS  PubMed  Google Scholar 

  33. Rustin P, Chretien D, Bourgeron T, Gerard B, Rotig A, Saudubray JM, Munnich A (1994) Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 228(1):35–51

    Article  CAS  PubMed  Google Scholar 

  34. Witt KA, Mark KS, Hom S, Davis TP (2003) Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression. Am J Physiol Heart Circ Physiol 285(6):H2820–H2831

    CAS  PubMed  Google Scholar 

  35. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  36. Collins RA, Gualano RC, Zosky GR, Atkins CL, Turner DJ, Colasurdo GN, Sly PD (2005) Hyperresponsiveness to inhaled but not intravenous methacholine during acute respiratory syncytial virus infection in mice. Respir Res 6:142

    Article  PubMed Central  PubMed  Google Scholar 

  37. Gomes RF, Shen X, Ramchandani R, Tepper RS, Bates JH (2000) Comparative respiratory system mechanics in rodents. J Appl Physiol 89(3):908–916

    CAS  PubMed  Google Scholar 

  38. Hirai T, McKeown KA, Gomes RF, Bates JH (1999) Effects of lung volume on lung and chest wall mechanics in rats. J Appl Physiol 86(1):16–21

    CAS  PubMed  Google Scholar 

  39. Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ (1992) Input impedance and peripheral inhomogeneity of dog lungs. J Appl Physiol 72(1):168–178

    Article  CAS  PubMed  Google Scholar 

  40. Jaenisch RB, Hentschke VS, Quagliotto E, Cavinato PR, Schmeing LA, Xavier LL, Dal Lago P (2011) Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure. J Appl Physiol 111(6):1664–1670

    Article  PubMed  Google Scholar 

  41. Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226(1):497–509

    CAS  PubMed  Google Scholar 

  42. Dudkina NV, Sunderhaus S, Boekema EJ, Braun HP (2008) The higher level of organization of the oxidative phosphorylation system: mitochondrial supercomplexes. J Bioenerg Biomembr 40(5):419–424

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Aguilera-Aguirre L, Bacsi A, Saavedra-Molina A, Kurosky A, Sur S, Boldogh I (2009) Mitochondrial dysfunction increases allergic airway inflammation. J Immunol 183(8):5379–5387

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Reddy PH (2006) Mitochondrial oxidative damage in aging and Alzheimer’s disease: implications for mitochondrially targeted antioxidant therapeutics. J Biomed Biotechnol 2006(3):31372

    PubMed Central  PubMed  Google Scholar 

  45. Reddy PH (2011) Mitochondrial dysfunction and oxidative stress in asthma: implications for mitochondria-targeted antioxidant therapeutics. Pharmaceuticals (Basel) 4(3):429–456

    Article  CAS  Google Scholar 

  46. da Cunha AA, Pauli V, Saciura VC, Pires MG, Constantino LC, de Souza B, Petronilho F, Rodrigues de Oliveira J, Ritter C, Romao PR, Boeck CR, Roesler R, Quevedo J, Dal-Pizzol F (2010) N-methyl-d-aspartate glutamate receptor blockade attenuates lung injury associated with experimental sepsis. Chest 137(2):297–302

    Article  PubMed  Google Scholar 

  47. Crouser ED (2004) Mitochondrial dysfunction in septic shock and multiple organ dysfunction syndrome. Mitochondrion 4(5–6):729–741

    Article  CAS  PubMed  Google Scholar 

  48. Fink MP (2002) Cytopathic hypoxia. Is oxygen use impaired in sepsis as a result of an acquired intrinsic derangement in cellular respiration? Crit Care Clin 18(1):165–175

    Article  CAS  PubMed  Google Scholar 

  49. Singer M, Brealey D (1999) Mitochondrial dysfunction in sepsis. Biochem Soc Symp 66:149–166

    CAS  PubMed  Google Scholar 

  50. Capaldi RA (1990) Structure and function of cytochrome c oxidase. Annu Rev Biochem 59:569–596

    Article  CAS  PubMed  Google Scholar 

  51. Bose R, Schnell CL, Pinsky C, Zitko V (1992) Effects of excitotoxins on free radical indices in mouse brain. Toxicol Lett 60(2):211–219. doi:10.1016/0378-4274(92)90276-P

    Article  CAS  PubMed  Google Scholar 

  52. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  53. Gupta RC, Milatovic D, Dettbarn WD (2001) Depletion of energy metabolites following acetylcholinesterase inhibitor-induced status epilepticus: protection by antioxidants. Neurotoxicology 22(2):271–282

    Article  CAS  PubMed  Google Scholar 

  54. Milatovic D, Zivin M, Gupta RC, Dettbarn WD (2001) Alterations in cytochrome c oxidase activity and energy metabolites in response to kainic acid-induced status epilepticus. Brain Res 912(1):67–78

    Article  CAS  PubMed  Google Scholar 

  55. Porta F, Takala J, Weikert C, Bracht H, Kolarova A, Lauterburg BH, Borotto E, Jakob SM (2006) Effects of prolonged endotoxemia on liver, skeletal muscle and kidney mitochondrial function. Crit Care 10(4):R118

    Article  PubMed Central  PubMed  Google Scholar 

  56. Pinho MA, Soares FS, Rocha LGC, de Pinho CA, da Silva LA, da Silveira PCL (2009) Efeitos preventivos e terapêuticos do exercício físico sobre lesão pulmonar e estresse oxidativo induzidopor bleomicina. Rev Bras Cineantropom Desempenho Hum 11(4):415–421

    Google Scholar 

  57. Venditti P, Di Meo S (1997) Effect of training on antioxidant capacity, tissue damage, and endurance of adult male rats. Int J Sports Med 18(7):497–502

    Article  CAS  PubMed  Google Scholar 

  58. Shiva S, Crawford JH, Ramachandran A, Ceaser EK, Hillson T, Brookes PS, Patel RP, Darley-Usmar VM (2004) Mechanisms of the interaction of nitroxyl with mitochondria. Biochem J 379(Pt 2):359–366

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Sommer SP, Sommer S, Sinha B, Walter D, Aleksic I, Gohrbandt B, Otto C, Leyh RG (2012) Glutathione preconditioning ameliorates mitochondria dysfunction during warm pulmonary ischemia–reperfusion injury. Eur J Cardiothorac Surg 41(1):140–148 discussion 148

    PubMed Central  PubMed  Google Scholar 

  60. Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, Brochard L, Brower R, Esteban A, Gattinoni L, Rhodes A, Slutsky AS, Vincent JL, Rubenfeld GD, Thompson BT, Ranieri VM (2012) The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 38(10):1573–1582

    Article  PubMed  Google Scholar 

  61. Gattinoni L, Pelosi P, Pesenti A, Brazzi L, Vitale G, Moretto A, Crespi A, Tagliabue M (1991) CT scan in ARDS: clinical and physiopathological insights. Acta Anaesthesiol Scand Suppl 95:87–94 discussion 94–96

    Article  CAS  PubMed  Google Scholar 

  62. Gregory TJ, Longmore WJ, Moxley MA, Whitsett JA, Reed CR, Fowler AA 3rd, Hudson LD, Maunder RJ, Crim C, Hyers TM (1991) Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest 88(6):1976–1981

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Perez-Gil J, Keough KM (1998) Interfacial properties of surfactant proteins. Biochim Biophys Acta 1408(2–3):203–217

    Article  CAS  PubMed  Google Scholar 

  64. Goerke J (1998) Pulmonary surfactant: functions and molecular composition. Biochim Biophys Acta 1408(2–3):79–89

    Article  CAS  PubMed  Google Scholar 

  65. Taeusch HW, Bernardino de la Serna J, Perez-Gil J, Alonso C, Zasadzinski JA (2005) Inactivation of pulmonary surfactant due to serum-inhibited adsorption and reversal by hydrophilic polymers: experimental. Biophys J 89(3):1769–1779

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Veldhuizen R, Possmayer F (2004) Phospholipid metabolism in lung surfactant. Subcell Biochem 37:359–388

    Article  CAS  PubMed  Google Scholar 

  67. Baker CS, Evans TW, Randle BJ, Haslam PL (1999) Damage to surfactant-specific protein in acute respiratory distress syndrome. Lancet 353(9160):1232–1237

    Article  CAS  PubMed  Google Scholar 

  68. Greene KE, Wright JR, Steinberg KP, Ruzinski JT, Caldwell E, Wong WB, Hull W, Whitsett JA, Akino T, Kuroki Y, Nagae H, Hudson LD, Martin TR (1999) Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med 160(6):1843–1850

    Article  CAS  PubMed  Google Scholar 

  69. Rodriguez-Capote K, Manzanares D, Haines T, Possmayer F (2006) Reactive oxygen species inactivation of surfactant involves structural and functional alterations to surfactant proteins SP-B and SP-C. Biophys J 90(8):2808–2821

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Santos FB, Nagato LK, Boechem NM, Negri EM, Guimaraes A, Capelozzi VL, Faffe DS, Zin WA, Rocco PR (2006) Time course of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury. J Appl Physiol 100(1):98–106

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Grants from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq–Brazil).

Conflict of interests

The authors declare that they have no conflict of interests.

Author information

Authors and Affiliations

  1. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    Maira J. da Cunha, Aline A. da Cunha, Emilene B. S. Scherer, Fernanda Rossato Machado, Samanta O. Loureiro, Fátima Guma & Angela T. S. Wyse

  2. Departamento de Fisioterapia, Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre – UFCSPA, Porto Alegre, RS, Brazil

    Rodrigo B. Jaenisch & Pedro Dal Lago

Authors
  1. Maira J. da Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aline A. da Cunha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emilene B. S. Scherer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fernanda Rossato Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Samanta O. Loureiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rodrigo B. Jaenisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fátima Guma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pedro Dal Lago
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Angela T. S. Wyse
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Angela T. S. Wyse.

Rights and permissions

Reprints and permissions

About this article

Cite this article

da Cunha, M.J., da Cunha, A.A., Scherer, E.B.S. et al. Experimental lung injury promotes alterations in energy metabolism and respiratory mechanics in the lungs of rats: prevention by exercise. Mol Cell Biochem 389, 229–238 (2014). https://doi.org/10.1007/s11010-013-1944-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1944-8

Keywords

Search

Navigation