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Reversal of haloperidol-induced orofacial dyskinesia and neuroinflammation by isoflavones

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Abstract

Background

Schizophrenia is a mental illness and its pharmacological treatment consists in the administration of antipsychotics like haloperidol. However, haloperidol often causes extrapyramidal motor disorders such as tardive dyskinesia (TD). So far, there is no effective treatment against TD and alternatives for it have been sought. Isoflafones have been studied as neuroprotector and inhibitor of monoamine oxidase enzyme. Thus, the objective is to evaluate the possible protective effect of isoflavones against the induction of involuntary movements induced by haloperidol in an animal model.

Methods and results

Male Wistar rats were treated with haloperidol (1 mg/kg/day) and/or isoflavones (80 mg/kg) for 28 days. Rats were submitted to behavioral evaluation to quantify vacuous chewing movements (VCM) and locomotor activity. In addition, the levels of pro-inflammatory cytokines were measured in the striatum. Haloperidol treatment reduced the locomotor activity and increased the number of VCM in rats. Co-treatment with isoflavones was able to reverse hypolocomotion and reduce the number of VCM. Besides, haloperidol caused significant increase in the proinflammatory cytokines (interleukin-1β:IL-1β, tumor necrosis factor-α: TNF-α and IL-6 and the co-treatment with isoflavones was able to reduce the levels of IL-1β and TNF-α, but not IL-6.

Conclusions

It is believed that the beneficial effect found with this alternative treatment is related to its anti-inflammatory potential and to the action on estrogen receptors (based on scientific literature findings). Finally, further studies are needed to elucidate the mechanisms of isoflavones in reducing motor disorders induced by antipsychotics.

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Acknowledgements

We acknowledge Universidade Franciscana for Izaviany Schmitz da Silva’s scientific initiation grant (PIBIC-UFN). Gilson Pires Dorneles is supported by a postdoctoral fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PNPD/CAPES). Carina Rodrigues Boeck and Pedro Roosevelt Torres Romao are grateful to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for the productivity scholarship granted.

Funding

There was no funding for this study.

Author information

Authors and Affiliations

  1. Mestrado em Ciências da Saúde e da Vida, Universidade Franciscana (UFN), Santa Maria, RS, Brazil

    Natália Fernandes Mezzomo, Valtieri Bortoluzzi de Lima, Carina Rodrigues Boeck & Luis Ricardo Peroza

  2. Curso de Biomedicina, Universidade Franciscana (UFN), Santa Maria, RS, Brazil

    Izaviani da Silva Schmitz & Larissa Finger Schaffer

  3. Laboratório de Imunologia Celular e Molecular, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil

    Gilson Pires Dorneles & Pedro Roosevelt Torres Romao

  4. Universidade Franciscana (UFN), 97010-032, Santa Maria, RS, Brazil

    Luis Ricardo Peroza

Authors
  1. Natália Fernandes Mezzomo
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  2. Izaviani da Silva Schmitz
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  3. Valtieri Bortoluzzi de Lima
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  4. Gilson Pires Dorneles
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  5. Larissa Finger Schaffer
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  6. Carina Rodrigues Boeck
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  7. Pedro Roosevelt Torres Romao
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  8. Luis Ricardo Peroza
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Contributions

NFM and LRP—development of experiments, data analysis, and writing manuscript. ISS, VBL, LFS and CRB—animal behavioral analysis and data analysis. GPD and PRTR—cytokine analysis and data analysis. All authors edited and approved the final version of the manuscript.

Corresponding author

Correspondence to Luis Ricardo Peroza.

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Authors declare that they do not hold any conflict of interest.

Ethical approval

The experimental protocol was approved by the Comissão de Ética no Uso de Animais (CEUA) of Universidade Franciscana (UFN) under the number 05/2017.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Mezzomo, N.F., da Silva Schmitz, I., de Lima, V.B. et al. Reversal of haloperidol-induced orofacial dyskinesia and neuroinflammation by isoflavones. Mol Biol Rep 49, 1917–1923 (2022). https://doi.org/10.1007/s11033-021-07003-7

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  • DOI: https://doi.org/10.1007/s11033-021-07003-7

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