4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice

  • Mutat Res Genet Toxicol Environ Mutagen. 2016 Jul;805:19-24. doi: 10.1016/j.mrgentox.2016.05.009.
Claudia Rodrigues Berno  1 ,  Barbara de Toledo Rós  1 ,  Ingridhy Ostaciana Maia Freitas da Silveira  2 ,  Henrique Rodrigues Coelho  3 ,  Andréia Conceição Milan Brochado Antoniolli  4 ,  Adilson Beatriz  5 ,  Dênis Pires de Lima  5 ,  Antônio Carlos Duenhas Monreal  6 ,  Fabricio Garmus Sousa  6 ,  Roberto da Silva Gomes  7 ,  Rodrigo Juliano Oliveira  8
Affiliations
  • 1. Center for Stem Cells, Cell Therapy and Genetic Toxicology Studies, Maria Aparecida Pedrossian University Hospital, EBSERH, Campo Grande, Mato Grosso do Sul, Brazil; Postgraduate Program in Pharmacy, Center for Biological and Health Sciences, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
  • 2. Postgraduate Program in Chemistry, Institute of Chemistry, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
  • 3. Postgraduate Program in Health and Development in the Midwestern Region, Medical School, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
  • 4. Center for Stem Cells, Cell Therapy and Genetic Toxicology Studies, Maria Aparecida Pedrossian University Hospital, EBSERH, Campo Grande, Mato Grosso do Sul, Brazil; Postgraduate Program in Health and Development in the Midwestern Region, Medical School, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
  • 5. Postgraduate Program in Pharmacy, Center for Biological and Health Sciences, UFMS, Campo Grande, Mato Grosso do Sul, Brazil; Postgraduate Program in Chemistry, Institute of Chemistry, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
  • 6. Postgraduate Program in Pharmacy, Center for Biological and Health Sciences, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
  • 7. Postgraduate Program in Chemistry, Institute of Chemistry, UFMS, Campo Grande, Mato Grosso do Sul, Brazil; College of Sciences and Technology (FACET), Federal University of Grande Dourados (UFGD), Dourados, MS, Brazil.
  • 8. Center for Stem Cells, Cell Therapy and Genetic Toxicology Studies, Maria Aparecida Pedrossian University Hospital, EBSERH, Campo Grande, Mato Grosso do Sul, Brazil; Postgraduate Program in Pharmacy, Center for Biological and Health Sciences, UFMS, Campo Grande, Mato Grosso do Sul, Brazil; Postgraduate Program in Health and Development in the Midwestern Region, Medical School, UFMS, Campo Grande, Mato Grosso do Sul, Brazil. Electronic address: [email protected].
PMID: 27402479 DOI: 10.1016/j.mrgentox.2016.05.009
Abstract

The analgesic drug dipyrone is used to treat side effects (including pain and fever) of Cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy.

Keywords
4-aminoantipyrine; DNA damage; cancer; dipyrone; immunomodulatory effect.
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