Molecular and Cellular Biochemistry

, Volume 350, Issue 1–2, pp 149–154 | Cite as

Inhibition of mitochondrial respiratory chain in the brain of rats after hepatic failure induced by acetaminophen

  • Jordana P. Panatto
  • Isabela C. Jeremias
  • Gabriela K. Ferreira
  • Ândrea C. Ramos
  • Natalia Rochi
  • Cinara L. Gonçalves
  • Juliana F. Daufenbach
  • Gabriela C. Jeremias
  • Milena Carvalho-Silva
  • Gislaine T. Rezin
  • Giselli Scaini
  • Emilio L. Streck
Article
First Online:
Received:
Accepted:

Abstract

Hepatic encephalopathy is an important cause of morbidity and mortality in patients with severe hepatic failure. This disease is clinically characterized by a large variety of symptoms including motor symptoms, cognitive deficits, as well as changes in the level of alertness up to hepatic coma. Acetaminophen is frequently used in animals to produce an experimental model to study the mechanisms involved in the progression of hepatic disease. The brain is highly dependent on ATP and most cell energy is obtained through oxidative phosphorylation, a process requiring the action of various respiratory enzyme complexes located in a special structure of the inner mitochondrial membrane. In this context, the authors evaluated the activities of mitochondrial respiratory chain complexes in the brain of rats submitted to acute administration of acetaminophen and treated with the combination of N-acetylcysteine (NAC) plus deferoxamine (DFX) or taurine. These results showed that acetaminophen administration inhibited the activities of complexes I and IV in cerebral cortex and that the treatment with NAC plus DFX or taurine was not able to reverse this inhibition. The authors did not observe any effect of acetaminophen administration on complexes II and III activities in any of the structures studied. The participation of oxidative stress has been postulated in the hepatic encephalopathy and it is well known that the electron transport chain itself is vulnerable to damage by reactive oxygen species. Since there was no effect of NAC + DFX, the effect of acetaminophen was likely to be due to something else than oxidative stress.

Keywords

Hepatic failure Mitochondria Respiratory chain N-Acetylcysteine Deferoxamine and taurine 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

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).

References

  1. 1.
    Diaz-Munoz M, Tapia R (1989) Functional changes of brain mitochondria during experimental hepatic encephalopathy. Biochem Pharmacol 38:3835–3841PubMedCrossRefGoogle Scholar
  2. 2.
    Gazzard BG, Price H, Dawson AM (1986) Detection of hepatic encephalopathy. Postgrad Med J 62:163–166PubMedCrossRefGoogle Scholar
  3. 3.
    Riordan SM, Williams R (1997) Treatment of hepatic encephalopathy. N Engl J Med 1:473–479CrossRefGoogle Scholar
  4. 4.
    Rama Rao KV, Jayakumar AR, Norenberg DM (2003) Ammonia neurotoxicity: role of the mitochondrial permeability transition. Metab Brain Dis 18:113–127PubMedCrossRefGoogle Scholar
  5. 5.
    Szymonik-Lesiuk S, Czechowska G, Stryjecka-Zimmer M, Słomka M, Madro A, Celiński K, Wielosz M (2003) Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. J Hepatobiliary Pancreat Surg 10:309–315PubMedCrossRefGoogle Scholar
  6. 6.
    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 34:471–477PubMedCrossRefGoogle Scholar
  7. 7.
    Pawa S, Ali S (2004) Liver necrosis and fulminant hepatic failure in rats: protection by oxyanionic form of tungsten. Biochim Biophys Acta 1688:210–222PubMedGoogle Scholar
  8. 8.
    Ganey PE, Luyendyk JP, Newport SW, Eagle TM, Maddox JF, Mackman N, Roth RA (2007) Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice. Hepatology 46:1177–1186PubMedCrossRefGoogle Scholar
  9. 9.
    Grypioti AD, Theocharis SE, Papadimas GK, Demopoulos CA, Papadopoulou-Daifoti Z, Basayiannis AC, Mykoniatis MG (2005) Platelet-activating factor (PAF) involvement in acetaminophen-induced liver toxicity and regeneration. Arch Toxicol 79:466–474PubMedCrossRefGoogle Scholar
  10. 10.
    Jamshidzadeh A, Baghban M, Azarpira N, Bardbori AM, Niknahad H (2008) Effects of tomato extract on oxidative stress induced toxicity in different organs of rats. Food Chem Toxicol 46:3612–3615PubMedCrossRefGoogle Scholar
  11. 11.
    Smith SW, Howland MA, Hoffman RS, Nelson LS (2008) Acetaminophen overdose with altered acetaminophen pharmacokinetics and hepatotoxicity associated with premature cessation of intravenous N-acetylcysteine therapy. Ann Pharmacother 42:1333–1339PubMedCrossRefGoogle Scholar
  12. 12.
    Cigremis Y, Turel H, Adiguzel K, Akgoz M, Kart A, Karaman M, Ozen H (2009) The effects of acute acetaminophen toxicity on hepatic mRNA expression of SOD, CAT, GSH-Px, and levels of peroxynitrite, nitric oxide, reduced glutathione, and malondialdehyde in rabbit. Mol Cell Biochem 323:31–38PubMedCrossRefGoogle Scholar
  13. 13.
    Ritter C, Reinke A, Andrades M, Martins MR, Rocha J, Menna-Barreto S, Quevedo J, Moreira JC, Dal-Pizzol F (2004) Protective effect of N-acetylcysteine and deferoxamine on carbon tetrachloride-induced acute hepatic failure in rats. Crit Care Med 32:2079–2083PubMedCrossRefGoogle Scholar
  14. 14.
    Ritter C, Andrades ME, Reinke A, Menna-Barreto S, Moreira JC, Dal-Pizzol F (2004) Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Crit Care Med 32:342–349PubMedCrossRefGoogle Scholar
  15. 15.
    Damiani CR, Benetton CA, Stoffel C, Bardini KC, Cardoso VH, Di Giunta G, Pinho RA, Dal-Pizool F, Streck EL (2007) Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodium. J Gastroenterol Hepatol 22:1846–1851PubMedCrossRefGoogle Scholar
  16. 16.
    Di-Pietro PB, Dias ML, Scaini G, Burigo M, Constantino L, Machado RA, Dal-Pizzol StreckEL (2008) Inhibition of brain creatine kinase activity after renal ischemia is attenuated by N-acetylcysteine and deferoxamine administration. Neurosci Lett 434:139–143PubMedCrossRefGoogle Scholar
  17. 17.
    Zapelini PH, Rezin GT, Cardoso MR, Ritter C, Klamt F, Moreira JC, Streck EL, Dal-Pizzol F (2008) Antioxidant treatment reverses mitochondrial dysfunction in a sepsis animal model. Mitochondrion 8:211–218PubMedCrossRefGoogle Scholar
  18. 18.
    Repine JE, Bast B, Lankhorst I (1997) Oxidative stress in chronic obstructive pulmonary disease. Am J Resp Crit Care Med 156:341–357PubMedGoogle Scholar
  19. 19.
    Halliwell B (1987) Oxidants and human disease: some new concepts. FASEB J 1:358–364PubMedGoogle Scholar
  20. 20.
    Halliwell B (1989) Protection against tissue damage in vivo by desferrioxamine: what is its mechanism of action? Free Radic Biol Med 7:645–651PubMedCrossRefGoogle Scholar
  21. 21.
    Wang GH, Jiang ZL, Fan XJ, Zhang L, Li X, Ke KF (2007) Neuroprotective effect of taurine against focal cerebral ischemia in rats possibly mediated by activation of both GABAA and glycine receptors. Neuropharmacology 52:1199–1209PubMedCrossRefGoogle Scholar
  22. 22.
    Richards DA, Lemos T, Whitton PS, Bowery NG (1995) Extracellular GABA in the ventrolateral thalamus of rats exhibiting spontaneous absence epilepsy: a microdialysis study. J Neurochem 65:1674–1680PubMedCrossRefGoogle Scholar
  23. 23.
    El Idrissi A, Trenkner E (1999) Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. J Neurosci 19:9459–9468PubMedGoogle Scholar
  24. 24.
    Kuiyama K (1980) Taurine as a neuromodulator. Fed Proc 39:2680–2684Google Scholar
  25. 25.
    Sturman JA (1993) Taurine in development. Physiol Rev 73:119–147PubMedGoogle Scholar
  26. 26.
    Tos-Luty S, Obuchowska-Przebi D, Latuszynska J, Tokarska-Rodak M, Haratym-Maj A (2003) Dermal and oral toxicity of malathion in rats. Ann Agric Environ Med 10:101–106PubMedGoogle Scholar
  27. 27.
    Carlson K, Ehrich M (1999) Organophosphorus compound induced modification of SH-SY5Y human neuroblastoma mitochondrial transmembrane potential. Toxicol Appl Pharmacol 160:33–42PubMedCrossRefGoogle Scholar
  28. 28.
    Beal MF (1998) Mitochondrial dysfunction in neurodegenerative diseases. Biochim Biophys Acta 1366:211–223PubMedCrossRefGoogle Scholar
  29. 29.
    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 30:235–243PubMedCrossRefGoogle Scholar
  30. 30.
    Lowry OH, Rosebough NG, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  31. 31.
    Cassina A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316PubMedCrossRefGoogle Scholar
  32. 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 153:23–26PubMedCrossRefGoogle Scholar
  33. 33.
    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 228:35–51PubMedCrossRefGoogle Scholar
  34. 34.
    Adam-Vizi V (2005) Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources. Antioxid Redox Signal 7:1140–1149PubMedCrossRefGoogle Scholar
  35. 35.
    Navarro A, Boveris A (2007) The mitochondrial energy transduction system and the aging process. Am. J Physiol Cell Physiol 292:670–686CrossRefGoogle Scholar
  36. 36.
    Sen T, Sen N, Jana S, Khan FH, Chatterjee U, Chakrabarti S (2007) Depolarization and cardiolipin depletion in aged rat brain mitochondria: relationship with oxidative stress and electron transport chain activity. Neurochem Int 50:719–725PubMedCrossRefGoogle Scholar
  37. 37.
    Gruno M, Peet N, Tein A, Salupere R, Sirotkina M, Valle J, Peetsalu A, Seppet EK (2008) Atrophic gastritis: deficient complex I of the respiratory chain in the mitochondria of corpus mucosal cells. J Gastroenterol 43:780–788PubMedCrossRefGoogle Scholar
  38. 38.
    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 281:855–860PubMedGoogle Scholar
  39. 39.
    Kelly JH, Koussayes T, Da-hertte HE, Chong MG, Shang TA, Wissenbrot HH, Sussman NC (1992) An improved model of acetaminophen-induced fulminant hepatic failure in dogs. Hepatol 15:329–335CrossRefGoogle Scholar
  40. 40.
    Francavilla A, Makowka L, Polimeno L, Barone M, Demetris J, Prelich J, Van Thiel DH, Starzl TE (1989) A dog model for acetaminophen-induced fulminant hepatic failure. Gastroenterology 96:470–478PubMedGoogle Scholar
  41. 41.
    Lauterburg BH (2000) Analgesics and glutathione. Am J Ther 9:225–233CrossRefGoogle Scholar
  42. 42.
    Felipo V, Butterworth RF (2002) Neurobiology of ammonia. Prog Neurobiol 67:259–279PubMedCrossRefGoogle Scholar
  43. 43.
    Rao KVR, Mawal YR, Qureshi IA (1997) Progressive decrease of cerebral cytochrome c oxidase activity in sparse-fur mice: role of acetyl-# -carnitine in restoring the ammonia-induced cerebral energy depletion. Neurosci Lett 224:83–86PubMedCrossRefGoogle Scholar
  44. 44.
    Qureshi K, Rao KV, Qureshi IA (1998) Differential inhibition by hyperammonemia of the electron transport chain enzymes in synaptosomes and nonsynaptic mitochondria in ornithine transcarbamylase-deficient spfmice: restoration by acetyl-l-carnitine. Neurochem Res 23:855–861PubMedCrossRefGoogle Scholar
  45. 45.
    Bai G, Murthy CRK, Norenberg MD (2000) Ammonia induces the mitochondrial permeability transition in cultured astrocytes. Soc Neurosci Abstr 26:1893Google Scholar
  46. 46.
    Brusilow SW, Traystman RJ (2000) Letter to editor. N Engl J Med 314:786Google Scholar
  47. 47.
    Takahashi H, Koehler RC, Brusilow SW, Traystman RJ (1991) Inhibition of brain glutamine accumulation prevents cerebral edema in hyperammonemic rats. Am J Physiol 261:H825–H829PubMedGoogle Scholar
  48. 48.
    Hawkins RA, Jessy J, Mans AM, De Joseph MR (1993) Effect of reducing brain glutamine synthesis on metabolic symptoms of hepatic encephalopathy. J Neurochem 60:1000–1006PubMedCrossRefGoogle Scholar
  49. 49.
    Zieminska E, Dolinska M, Lazarewicz JW, Albrecht J (2000) Induction of permeability transition and swelling of rat brain mitochondria by glutamine. Neurotoxicology 21:295–300PubMedGoogle Scholar
  50. 50.
    Mehrotra S, Kakkar P, Viswanathan PN (1991) Mitochondrial damage by active oxygen species in vitro. Free Rad Biol Med 10:277–286PubMedCrossRefGoogle Scholar
  51. 51.
    Konarski M, Stewart RE, McCarty R (1990) Predictability of chronic intermittent stress: effects on sympathetic-adrenal medullary responses of laboratory rats. Behav Neural Biol 53:231–243CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Jordana P. Panatto
    • 1
  • Isabela C. Jeremias
    • 1
  • Gabriela K. Ferreira
    • 1
  • Ândrea C. Ramos
    • 1
  • Natalia Rochi
    • 1
  • Cinara L. Gonçalves
    • 1
  • Juliana F. Daufenbach
    • 1
  • Gabriela C. Jeremias
    • 1
  • Milena Carvalho-Silva
    • 1
  • Gislaine T. Rezin
    • 1
  • Giselli Scaini
    • 1
  • Emilio L. Streck
    • 1
  1. 1.Laboratório de Fisiopatologia Experimental and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Programa de Pós-graduação em Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciúmaBrazil

Personalised recommendations