Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 387, Issue 9, pp 837–848 | Cite as

Effects of the compounds resveratrol, rutin, quercetin, and quercetin nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice

  • Tania E. Schwingel
  • Caroline P. Klein
  • Natalia F. Nicoletti
  • Cristiana L. Dora
  • Gabriela Hadrich
  • Cláudia G. Bica
  • Tiago G. Lopes
  • Vinicius Duval da Silva
  • Fernanda B. Morrone
Original Article

Abstract

Oxaliplatin (OXA) is a platinum compound widely used in the treatment of some solid tumors, especially colorectal cancer. Despite its usefulness, oxaliplatin-associated neurotoxicity represents the main dose-limiting factor of this drug, and until now, there is no suitable treatment. Chemotherapy with oxaliplatin also increases the rate of developing hepatic damages with inflammatory activity, termed chemotherapy-associated steatohepatitis (CASH). In the present study, we aimed to compare the effects of a series of antioxidant compounds on simultaneous development of oxaliplatin-induced hepato- and neurotoxicity in mice. Mice BALB/c were treated with oxaliplatin for 6 weeks, 10 mg/kg, intraperitoneally, resulting in mechanical allodynia and hepatic steatosis. We administered the following antioxidant compounds—rutin (RT) (20 mg/kg), resveratrol (RVS) (100 mg/kg), quercetin (QT) (20 mg/kg), and quercetin nanoemulsion (NQT) (20 mg/kg)—daily by gavage to BALB/c, and N-acetylcysteine (NAC) was used as positive control. Treatments with RSV, RUT, or NQT were able to prevent mechanical allodynia when compared to the OXA group, and this effect was associated with decreased c-Fos immunopositivity in the lumbar spinal cord. Regarding the effects on steatohepatitis, RVS, QT, and NQT almost completely reversed the mean liver weight increase induced by OXA. In accordance with these previous data, histological evaluation indicated attenuation of all features of hepatic steatosis evaluated in RSV, RUT, QT, and NQT groups. These compounds were able to reduce the immunopositivity for the apoptosis marker caspase-3. On the other hand, only QT and NQT treatments were able to reduce neutrophil migration measured by myeloperoxidase (MPO) activity. These results suggest that the compounds tested, RSV, RUT, QT, and NQT, would be useful for the clinical treatment of neuro- and hepatoxicity induced by oxaliplatin.

Keywords

CASH Neuropathy Polyphenol compounds Oxaliplatin 

Notes

Acknowledgments

This work was supported by FINEP research grant “Implantação, Modernização e Qualificação de Estrutura de Pesquisa da PUCRS” (PUCRSINFRA) # 01.11.0014-00 and PRONEM / FAPERGS grant 11/2037-9. The authors would like to thank Dr. Maria Martha Campos for her valuable critical advice. We thank Dr. Léder Leal Xavier for the use of the laboratory facilities.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Tania E. Schwingel
    • 1
  • Caroline P. Klein
    • 1
  • Natalia F. Nicoletti
    • 1
  • Cristiana L. Dora
    • 4
  • Gabriela Hadrich
    • 4
  • Cláudia G. Bica
    • 5
  • Tiago G. Lopes
    • 3
  • Vinicius Duval da Silva
    • 3
  • Fernanda B. Morrone
    • 1
    • 2
    • 6
  1. 1.Programa de Pós Graduação em Biologia Celular e MolecularPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  2. 2.Instituto de Toxicologia e FarmacologiaPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  3. 3.Laboratório de Patologia do Hospital São Lucas da PUCRSPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  4. 4.Programa de Pós-Graduação em Ciências da Saúde, Laboratório de Nanotecnologia Aplicada a Saúde, Universidade Federal do Rio GrandeRio GrandeBrazil
  5. 5.Programa de Pós-graduação em PatologiaUniversidade Federal de Ciências da Saúde de Porto AlegrePorto AlegreBrazil
  6. 6.Faculdade de FarmáciaPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil

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