Skip to main content
SpringerLink
Log in

The effects of isoniazid on hippocampal NMDA receptors: Protective role of Erdosteine

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

Abstract

Isoniazid (INH) has neurotoxic effects such as seizure, poor concentration, subtle reduction in memory, anxiety, depression and psychosis. INH-induced toxic effects are thought to be through increased oxidative stress, and these effects have been shown to be prevented by antioxidant therapies in various organs. Increased oxidative stress may be playing a role in these neurotoxic effects. N-methyl D-aspartat receptors (NMDA) are a member of the ionotropic group of glutamate receptors. These receptors are involved in a wide variety of processes in the central nervous system including synaptogenesis, synaptic plasticity, memory and learning. Erdosteine is a potent antioxidant and mucolytic agent. We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH. In the present study, compared to control group, NMDAR2A (NR2A) receptors were significantly decreased and malondialdehyde (MDA), end product of lipid peroxidation, production was significantly increased in INH-treated group. On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production. In conclusion, decreasing NR2A receptors in hippocampus and increasing lipid peroxidation correlates with the degree of oxidative effects of INH and erdosteine protects above effect of INH on NR2A receptors and membrane damage due to lipid peroxidation by its antioxidant properties.

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

Similar content being viewed by others

References

  1. Sarich TC, Youssefi M, Zhou T, Adams SP, Wall RA: Wright JM: Role of hydrazine in the mechanism of isoniazid hepatotoxicity in rabbits. Arch Toxicol 70: 835–840, 1996

    Article  PubMed  Google Scholar 

  2. Attri S, Rana SV, Vaiphei K, Sodhi CP, Katyal R, Goel RC, Nain CK, Singh K: Isoniazid- and rifampicin-induced oxidative hepatic injury-protection by N-acetylcysteine. Hum Exp Toxicol 19: 517–522, 2000

    Article  PubMed  Google Scholar 

  3. Martinjak-Dvorsek I, Gorjup V, Horvat M, Noc M: Acute isoniazid neurotoxicity during preventive therapy. Crit Care Med 28: 567–568, 2000

    Article  PubMed  Google Scholar 

  4. Shah BR, Santucci K, Sinert R, Steiner P: Acute isoniazid neurotoxicity in an urban hospital. Pediatrics 95: 700–704, 1995

    PubMed  Google Scholar 

  5. Bal’tseva LB, Mel’nik GV, Man’ko VP: The elimination of chemotherapy side effects in pulmonary tuberculosis patients. Vrach Delo 4: 71–73, 1990

    PubMed  Google Scholar 

  6. Olson KR, Kearney TE, Dyer JE, Benowitz NL, Blanc PD: Seizures associated with poisoning and drug overdose. Am J Emerg Med 12: 392–395, 1994

    Article  PubMed  Google Scholar 

  7. Anderson D, Anderson V, Pentland L, Sawyer S, Starr M, Johnson PD: Attentional function in secondary school students receiving isoniazid prophylaxis for tuberculosis infection. Epidemiol Infect 124: 97–101, 2000

    Article  PubMed  Google Scholar 

  8. Ramos A, Portero JL, Murillas J, Losada I, Martin H: Isoniazid-induced toxic encephalopathy. Rev Neurol 26: 160, 1998

    PubMed  Google Scholar 

  9. Sievers ML, Herrier RN: Treatment of acute isoniazid toxicity. Am J Hosp Pharm 32: 202–206, 1975

    PubMed  Google Scholar 

  10. Wason S, Lacouture PG, Lovejoy FHJr: Single high-dose pyridoxine treatment for isoniazid overdose. JAMA 246: 1102–1104, 1981

    Article  PubMed  Google Scholar 

  11. Reilly RH, Killam KF, Jenney EH, Marshall WH, Tausig T, Apter NS, Pfeiffer CC: Convulsant effects of isoniazid. J Am Med Assoc 152: 1317–1321, 1953

    PubMed  Google Scholar 

  12. Fadillioglu E, Yilmaz HR, Erdogan H, Sogut S: The activities of tissue xanthine oxidase and adenosine deaminase and the levels of hydroxyproline and nitric oxide in rat hearts subjected to doxorubicin: Protective effect of erdosteine. Toxicology 191: 153–158, 2003

    Article  PubMed  Google Scholar 

  13. Yagmurca M, Fadillioglu E, Erdogan H, Ucar M, Sogut S, Irmak MK: Erdosteine prevents doxorubicin-induced cardiotoxicity in rats. Pharmacol Res 48: 377–382, 2003

    Article  PubMed  Google Scholar 

  14. Sogut S, Ozyurt H, Armutcu F, Kart L, Iraz M, Akyol O, Ozen S, Kaplan S, Temel I, Yildirim Z: Erdosteine prevents bleomycin-induced pulmonary fibrosis in rats. Eur J Pharmacol 494: 213–220, 2004

    Article  PubMed  Google Scholar 

  15. Andrzheiuk NI, Smirnova NA, Narovlianskaia SE, Novoselova VP, Kruglova EG: The pro-fibrotic and pro-oxidant action of isoniazid. Probl Tuberk 8: 7–11, 1990

    PubMed  Google Scholar 

  16. Amacher DE, Schomaker SJ: Ethylmorphine N-demethylase activity as a marker for cytochrome P450 CYP3A activity in rat hepatic microsomes. Toxicol Lett 94: 115–125, 1998

    Article  PubMed  Google Scholar 

  17. Thomas BH, Whitehouse LW, Zeitz W: Metabolism of [14C]acetyliso- niazid and [14C]acetylhydrazine by the rat and rabbit. Fundam Appl Toxicol 4: 646–653, 1984

    Article  PubMed  Google Scholar 

  18. Jones HB, Cavanagh JB: Comparison between the early changes in isoniazid intoxication and the chromatolytic response to nerve ligation in spinal ganglion cells of the rat. Neuropathol Appl Neurobiol 7: 489–501, 1981

    PubMed  Google Scholar 

  19. Draper HH, Hadley M: Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186: 421–431, 1990

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  21. Takagi N, Sasakawa K, Besshoh S, Miyake-Takagi K, Takeo S: Transient ischemia enhances tyrosine phosphorilation and binding of the NMDA receptor to the Src homology 2 domain of phosphatidylinositol 3-kinase in the rat hippocampus. J Neurochem 84: 67–76, 2003

    Article  PubMed  Google Scholar 

  22. Gurd JW, Bissoon N, Beesley PW, Nakazawi T, Yamamoto I, Vannucci SC: Differential effects of hypoxia-ischemia on subunit expression and tyrosine phosphorilation of the NMDAR in 7-and 21-day-old rats. J Neurochem 82: 848–856, 2002

    Article  PubMed  Google Scholar 

  23. Wittenberg GM, Tsien JZ: An emerging molecular and cellular framework for memory processing by the hippocampus. Trends neurosci 25: 501–505, 2002

    Article  PubMed  Google Scholar 

  24. Meador-Woodruff JH, Healy DJ: Glutamate receptor expression in schizophrenic brain. Brain Res Rev 31: 288–294, 1999

    Article  Google Scholar 

  25. Lipton SA, Rosenberg PA: Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330: 613–622, 1994

    PubMed  Google Scholar 

  26. Hosoe H, Kaise T, Ohmori K: Effects on the reactive oxygen species of erdosteine and its metabolite in vitro. Arzneimittelforschung 52: 435–440, 2002

    PubMed  Google Scholar 

  27. Hosoe H, Kaise T, Ohmori K: Erdosteine enhances mucociliary clearance in rats with and without airway inflammation. J Pharmacol Toxicol Methods 40: 165–171, 1998

    Article  PubMed  Google Scholar 

  28. Hayashi K, Hosoe H, Kaise T, Ohmori K: Protective effect of erdosteine against hypochlorous acid-induced acute lung injury and lipopolysaccharide-induced neutrophilic lung inflammation in mice. J Pharm Pharmacol 52: 1411–1416, 2000

    Article  PubMed  Google Scholar 

  29. Reiter RJ, Guerrero JM, Garcia JJ, Acuna-Castroviejo D: Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin. Ann NY Acad Sci 854: 410–424, 1998

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Suleyman Demirel University, Faculty of Medicine, Morfoloji Binasi, Cunur-Isparta, 32260, Turkey

    Ekrem Cicek, Osman Gokalp, M. Kaya Ozer & Efkan Uz

  2. Department of Biochemistry, Suleyman Demirel University, Faculty of Medicine, Isparta, Turkey

    Recep Sutcu & Namik Delibas

  3. Department of Medical Biology and Genetics, Suleyman Demirel University, Faculty of Medicine, Isparta, Turkey

    H. Ramazan Yilmaz & Nurten Ozcelik

Authors
  1. Ekrem Cicek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Recep Sutcu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Osman Gokalp
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Ramazan Yilmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Kaya Ozer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Efkan Uz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nurten Ozcelik
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Namik Delibas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Osman Gokalp.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cicek, E., Sutcu, R., Gokalp, O. et al. The effects of isoniazid on hippocampal NMDA receptors: Protective role of Erdosteine. Mol Cell Biochem 277, 131–135 (2005). https://doi.org/10.1007/s11010-005-5778-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-5778-x

Keywords

Search

Navigation