Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

  • Katiane Roversi
  • Dalila M. Benvegnú
  • Karine Roversi
  • Fabíola Trevizol
  • Luciana T. Vey
  • Fabiana Elias
  • Rafael Fracasso
  • Mariana H. Motta
  • Roseane F. Ribeiro
  • Bruna dos S. Hausen
  • Rafael N. Moresco
  • Solange C. Garcia
  • Cristiane B. da Silva
  • Marilise E. Burger
Research Paper
First Online:
Received:
Accepted:

Abstract

Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups (n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

Keywords

Cellular integrity Haloperidol Polymeric nanocapsules Nanotoxicology Oxidative stress Nanomedicine 
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Notes

Acknowledgments

The authors are grateful to CNPq (Edital Nanotecnologia MCT/CNPq 62/2010 no. 577450) for the financial support, to CAPES (K. R.; F. T. and B. S. H.), CNPq (Kr. R. and L. T. V.) for the fellowships, as well as for the research Grants (CNPq S. C. G. and M. E. B.).

Conflict of interest

Authors report no conflicts of interest.

Compliance with Ethical Standards

The experimental protocol of this study was approved by the Animal Ethics Committee of Universidade Federal de Santa Maria (CIETEA-22/2010), affiliated to CONCEA, and adhered to the ‘‘Principles of Laboratory Animal Care’’ and international rules of ethics in research.

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Katiane Roversi
    • 1
  • Dalila M. Benvegnú
    • 3
  • Karine Roversi
    • 2
  • Fabíola Trevizol
    • 1
  • Luciana T. Vey
    • 2
  • Fabiana Elias
    • 3
  • Rafael Fracasso
    • 5
  • Mariana H. Motta
    • 4
  • Roseane F. Ribeiro
    • 4
  • Bruna dos S. Hausen
    • 4
  • Rafael N. Moresco
    • 4
  • Solange C. Garcia
    • 5
  • Cristiane B. da Silva
    • 4
  • Marilise E. Burger
    • 1
    • 2
  1. 1.Programa de Pós-Graduação em FarmacologiaUniversidade Federal de Santa MariaSanta MariaBrazil
  2. 2.Departamento de Fisiologia e Farmacologia, Centro de Ciências da SaúdeUniversidade Federal de Santa Maria (UFSM)Santa MariaBrazil
  3. 3.Bioquímica e FarmacologiaUniversidade Federal da Fronteira Sul (UFFS)RealezaBrazil
  4. 4.Programa de Pós-Graduação em Ciências FarmacêuticasUniversidade Federal de Santa MariaSanta MariaBrazil
  5. 5.Programa de Pós-Graduação em Ciências FarmacêuticasUniversidade Federal do Rio Grande do SulPorto AlegreBrazil

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