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Ketamine treatment protects against oxidative damage and the immunological response induced by electroconvulsive therapy

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Abstract

Background

Electroconvulsive therapy (ECT) is often recommended for major depressive disorder (MDD) for those who do not respond to the first and second antidepressant trials. A combination of two therapies could improve antidepressant efficacy. Thus, this study aimed to investigate the synergistic effects of ECT combined to antidepressants with a different mechanism of action.

Methods

Rats were treated once a day, for five days with ketamine (5 mg/kg), fluoxetine (1 mg/kg), and bupropion (4 mg/kg) alone or in combination with ECT (1 mA; 100 V). After, oxidative damage and antioxidant capacity were assessed in the prefrontal cortex (PFC) and hippocampus, and pro-inflammatory cytokines levels were evaluated in the serum.

Results

ECT alone increased lipid peroxidation in the PFC and hippocampus. In the PFC of rats treated with ECT in combination with fluoxetine and bupropion, and in the hippocampus of rats treated with ECT combined with ketamine and bupropion there was a reduction in the lipid peroxidation. The nitrite/nitrate was increased by ECT alone but reverted by combination with ketamine in the hippocampus. Superoxide dismutase (SOD) was increased by ECT and maintained by fluoxetine and bupropion in the PFC. ECT alone increased interleukin-1β (IL-1β) and the administration of ketamine was able to revert this increase showing a neuroprotective effect of this drug when in combination with ECT.

Conclusion

The treatment with ECT leads to an increase in oxidative damage and alters the immunological system. The combination with ketamine was able to protect against oxidative damage and the immunological response induced by ECT.

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Funding

The Translational Psychiatry Program (USA) is funded by the Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth). Translational Psychiatry Laboratory (Brazil) is one of the members of the Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC). Its research is supported by Grants from CNPq (JQ and GZR), FAPESC (JQ and GZR); Instituto Cérebro e Mente (JQ and GZR) and UNESC (JQ and GZR). JQ is a 1A CNPq Research Fellow.

Author information

Authors and Affiliations

  1. Experimental Neurology Laboratory, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil

    Cinara Ludvig Gonçalves

  2. Translational Psychiatry Laboratory, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, 88806-000, Brazil

    Helena Mendes Abelaira, Thayse Rosa, Airam Barbosa de Moura, Deise Cristina Veron, Laura Araújo Borba, Maria Eduarda Mendes Botelho, Zuleide Maria Ignácio, João Quevedo & Gislaine Zilli Réus

  3. Neurobiology of Metabolic and Inflammatory Processes Laboratory, Graduate Program in Health Sciences, University of South Santa Catarina, Tubarão, SC, Brazil

    Mariana Pereira Goldim, Leandro Garbossa, Maria Eduarda Fileti & Fabricia Petronilho

  4. Laboratory of Physiology, Pharmacology and Psychopathology, Campus Chapecó, Federal University of South Frontier (UFFS), Chapecó, Santa Catarina, Brazil

    Zuleide Maria Ignácio

  5. State Secretary for Justice and Citizenship of Santa Catarina, Chapecó, Brazil

    Zuleide Maria Ignácio

  6. Department of Psychiatry and Behavioral Sciences, Center of Excellence On Mood Disorders, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    João Quevedo

  7. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    João Quevedo

  8. Neuroscience Graduate Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center At Houston (UTHealth), Houston, TX, USA

    João Quevedo

Authors
  1. Cinara Ludvig Gonçalves
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  2. Helena Mendes Abelaira
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  3. Thayse Rosa
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  7. Maria Eduarda Mendes Botelho
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  12. Zuleide Maria Ignácio
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  14. Gislaine Zilli Réus
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Contributions

All authors participated in the design and interpretation of the studies, analyzed the data and review of the manuscript; HMA, TR, ABM, ZMI, and LAB applied the ECT protocol and drugs administration in the animals. MEMB and MPG conducted the oxidative stress analysis; LG, MEF, and FP carried the cytokines analyzes; CLG, DCV, JQ, and GZR wrote the manuscript.

Corresponding author

Correspondence to Gislaine Zilli Réus.

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Gonçalves, C.L., Abelaira, H.M., Rosa, T. et al. Ketamine treatment protects against oxidative damage and the immunological response induced by electroconvulsive therapy. Pharmacol. Rep 73, 525–535 (2021). https://doi.org/10.1007/s43440-020-00200-4

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