Skip to main content
SpringerLink
Log in

Inhibition of mitochondrial respiratory chain in the brain of rats after renal ischemia is prevented by N-acetylcysteine and deferoxamine

  • Original Paper
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

We evaluated the activities of mitochondrial respiratory chain complexes in the brain of rats after renal ischemia and the effect of administration of the antioxidants N-acetylcysteine (NAC) and deferoxamine (DFX). The rats were divided into the groups: sham (control) or renal ischemia treated with saline, NAC 20 mg/kg, DFX 20 mg/kg or both antioxidants. Complex I activity was inhibited in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 1 and 6 h after renal ischemia and that the treatment with a combination of NAC and DFX prevented such effect. Complex I activity was not altered in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 12 h after renal ischemia. Complexes II and III activities were not altered in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 1, 6 and 12 h after renal ischemia. Complex IV activity was inhibited in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 1 h after renal ischemia, but the treatment with the combination of NAC and DFX was able to prevent this inhibition. Complex IV activity was not altered in hippocampus, striatum, prefrontal cortex and cerebral cortex of rats 6 and 12 h after renal ischemia. These results suggest that the inhibition of mitochondrial respiratory chain after renal ischemia might play a role in the pathogenesis of uremic encephalopathy.

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

Similar content being viewed by others

References

  • Barja G, Herrero A (1998) Localization at complex I and mechanism of the higher free radical production of brain nonsynaptic mitochondria in the short-lived rat than in the longevous pigeon. J Bioenerg Biomembr 30:235–243

    Article  CAS  PubMed  Google Scholar 

  • Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Ver 78:547–581

    CAS  Google Scholar 

  • Blass JP (2001) Brain metabolism and brain disease: is metabolic deficiency the proximate cause of Alzheimer dementia? J Neurosci Res 66:851–856

    Article  CAS  PubMed  Google Scholar 

  • Boekema EJ, Braun HP (2006) Supramolecular structure of the mitochondrial oxidative phosphorylation system. J Chem Biol 282(1):1–4

    Article  Google Scholar 

  • Bouré T, Vanholder R (2004) Biochemical and clinical evidence for uremic toxicity. Artif Organs 28:248–253

    Article  PubMed  Google Scholar 

  • Brennan WA, Bird ED, Aprille JR (1985) Regional mitochondrial respiratory activity in Huntington´s disease brain. J Neurochem 44:1948–1950

    Article  CAS  PubMed  Google Scholar 

  • Brouns R, De Deyn PP (2004) Neurological complications in renal failure: a review. Clin Neurol Neurosurg 107(1):1–16

    Article  CAS  PubMed  Google Scholar 

  • Burn DJ, Bates D (1998) Neurology and the kidney. J Neurol Neurosurg Psychiatr 65:810–821

    Article  CAS  PubMed  Google Scholar 

  • Carbonell T, Rama R (2007) Oxidative stress and early neurological deterioration in ischemic stroke. Curr Med Chem 14:857–874

    Article  CAS  PubMed  Google Scholar 

  • Casademont J, Rodriguez-Santiago B, Miró O, Beato A, López S, Nunes V, Cardellach F (2005) Mitochondrial respiratory chain in brain homogenates: activities in different brain areas in patients with Alzheimer’s disease. Aging Clin Exp Res 1:1–7

    Google Scholar 

  • Cassina A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316

    Article  CAS  PubMed  Google Scholar 

  • Damiani CR, Benetton CA, Stoffel C, Bardini KC, Cardoso VH, Di Giunta G, Pinho RA, Dal-Pizzol F, Streck EL (2007) Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodium. J Gastroenterol Hepatol 22:1846–1851

    Article  CAS  PubMed  Google Scholar 

  • Di-Pietro PB, Dias ML, Scaini G, Burigo M, Constantino L, Machado RA, Dal-Pizzol F, Streck EL (2008) Inhibition of brain creatine kinase activity after renal ischemia is attenuated by N-acetylcysteine and deferoxamine administration. Neurosci Lett 434:139–143

    Article  CAS  PubMed  Google Scholar 

  • Ellis CE, Murphy EJ, Mitchell DC, Golovko MY, Scaglia F, Barceló-Coblijn GC, Nussbaum RL (2005) Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol 22:10190–10201

    Article  Google Scholar 

  • 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 153:23–36

    Article  CAS  PubMed  Google Scholar 

  • Gassner B, Wuthrich A, Scholtysik G, Solioz M (1997) The pyrethroids permethrin and cyhalothrin are potent inhibitors of the mitochondrial complex I. J Pharmacol Exp Ther 281:855–860

    CAS  PubMed  Google Scholar 

  • Gonzalez-Flecha B, Cutrin JC, Boveris A (1993) Time course and mechanism of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. J Clin Invest 91:456–464

    Article  CAS  PubMed  Google Scholar 

  • Heales SJ, Bolaños JP, Stewart VC, Brookes PS, Land JM, Clark JB (1999) Nitric oxide, mitochondria and neurological disease. Biochim Biophys Acta 1410:215–228

    Article  CAS  PubMed  Google Scholar 

  • Ikeda M, Prachasilchaim W, Burne-Taney MJ, Rabb H, Yokota-Ikeda N (2006) Ischemic acute tubular necrosis models and drug discovery: a focus on cellular inflammation. Drug Discov Today 11:364–370

    Article  CAS  PubMed  Google Scholar 

  • Keeney PM, Xie J, Capaldi RA, Bennett JP Jr (2006) Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci 19:5256–5264

    Article  Google Scholar 

  • Lowry OH, Rosebough NG, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Massicotte C, Knight K, Van der Schyf CJ, Jortner BS, Ehrich M (2005) Effects of organophosphorus compounds on ATP production, mitochondrial integrity in cultured cells. Neurotox Res 7(3):203–217

    Article  CAS  PubMed  Google Scholar 

  • Monsalve M, Borniquel S, Valle I, Lamas S (2007) Mitochondrial dysfunction in human pathologies. Fronti Biosci 12:1131–1153

    Article  CAS  Google Scholar 

  • Navarro A, Boveris A (2004) Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging. Am J Physiol Regul Integr Comp Physiol 287:R1244–R1249

    CAS  PubMed  Google Scholar 

  • Navarro A, Gomez C, Sanchez-Pino MJ, González H, Bández MJ, Boveris AD, Boveris A (2005) Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. Am J Physiol Regul Integr Comp Physiol 289:R1392–R1399

    CAS  PubMed  Google Scholar 

  • Ritter C, Andrades ME, Reinke A, Menna-Barreto S, Moreira JC, Dal-Pizzol F (2004a) Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Crit Care Med 32:342–349

    Article  CAS  PubMed  Google Scholar 

  • Ritter C, Reinke A, Andrades M, Martins MR, Rocha J, Menna-Barreto S, Quevedo J, Moreira JC, Dal-Pizzol F (2004b) Protective effect of N-acetylcysteine and deferoxamine on carbon tetrachloride-induced acute hepatic failure in rats. Crit Care Med 32:2079–2083

    Article  CAS  PubMed  Google Scholar 

  • Ritter C, 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 34:471–477

    Article  CAS  PubMed  Google Scholar 

  • Rizzardini M, Lupi M, Mangolini A, Babetto E, Ubezio P, Cantoni L (2006) Neurodegeneration induced by complex I inhibition in a cellular model of familial amyotrophic lateral sclerosis. Brain Res Bull 4:465–474

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Schurr A (2002) Energy metabolism, stress hormones and neural recovery from cerebral ischemia/hypoxia. Neurochem Int 41:1–8

    Article  CAS  PubMed  Google Scholar 

  • Sener G, Sakarcan A, Sehirli O, Ekşioğlu-Demiralp E, Sener E, Ercan F, Gedik N, Yeğen BC (2007) Chronic renal failure-induced multiple-organ injury in rats is alleviated by the selective CysLT1 receptor antagonist montelukast. Prostaglandins Other Lipid Mediat 83:257–267

    Article  CAS  PubMed  Google Scholar 

  • Shang T, Kotamraju S, Kalivendi SV, Hillard CJ, Kalyanaraman B (2004) 1-Methyl-4-phenylpyridinium-induced apoptosis in cerebellar granule neurons is mediated by transferrin receptor iron-dependent depletion of tetrahydrobiopterin and neuronal nitric-oxide synthase-derived superoxide. J Biol Chem 18:19099–19112

    Article  Google Scholar 

  • Sherer TB, Betarbet R, Kim JH, Greenamyre JT (2003) Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol 179:9–16

    Article  CAS  PubMed  Google Scholar 

  • Singri N, Ahya SN, Levin ML (2003) Acute renal failure. JAMA 289:747–751

    Article  PubMed  Google Scholar 

  • Streck EL, Feier G, Búrigo M, Franzon R, Dal-Pizzol F, Quevedo J, Wyse AT (2006) Effects of electroconvulsive seizures on Na+, K+-ATPase activity in the rat hippocampus. Neurosci Lett 404:254–257

    Article  CAS  PubMed  Google Scholar 

  • Streck EL, Amboni G, Scaini G, Di-Pietro PB, Rezin GT, Valvassori SS, Luz G, Kapczinski F, Quevedo J (2008) Brain creatine kinase activity in an animal model of mania. L Sci 82:424–429

    Article  CAS  Google Scholar 

  • Sullivan PG, Dragicevic NB, Deng JH, Bai Y, Dimayuga E, Ding Q, Chen Q, Bruce-Keller AJ, Keller JN (2004) Proteasome inhibition alters neural mitochondrial homeostasis and mitochondria turnover. J Biol Chem 20:20699–20707

    Article  Google Scholar 

  • Thadhani R, Pascual M, Bonventre JV (1996) Acute renal failure. N Engl J Med 334:1448–1460

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by grants from Programa de Pós-graduação em Ciências da Saúde – Universidade do Extremo Sul Catarinense (UNESC) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Author information

Authors and Affiliations

  1. Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000, Criciúma, SC, Brazil

    Paulo R. Barbosa, Mariane R. Cardoso, Juliana F. Daufenbach, Cinara L. Gonçalves, Roberta A. Machado, Clarissa A. Roza, Giselli Scaini, Gislaine T. Rezin, Patricia F. Schuck, Felipe Dal-Pizzol & Emilio L. Streck

Authors
  1. Paulo R. Barbosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mariane R. Cardoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juliana F. Daufenbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cinara L. Gonçalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberta A. Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Clarissa A. Roza
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giselli Scaini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gislaine T. Rezin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Patricia F. Schuck
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Felipe Dal-Pizzol
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Emilio L. Streck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emilio L. Streck.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barbosa, P.R., Cardoso, M.R., Daufenbach, J.F. et al. Inhibition of mitochondrial respiratory chain in the brain of rats after renal ischemia is prevented by N-acetylcysteine and deferoxamine. Metab Brain Dis 25, 219–225 (2010). https://doi.org/10.1007/s11011-010-9187-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-010-9187-9

Keywords

Search

Navigation