title: 4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice.
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.
authors.affiliation: 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.
authors.forename: Claudia Rodrigues
authors.initials: CR
authors.lastname: Berno
authors.affiliation: 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.
authors.forename: Barbara de Toledo
authors.initials: Bde T
authors.lastname: Rós
authors.affiliation: Postgraduate Program in Chemistry, Institute of Chemistry, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
authors.forename: Ingridhy Ostaciana Maia Freitas
authors.initials: IO
authors.lastname: da Silveira
authors.affiliation: Postgraduate Program in Health and Development in the Midwestern Region, Medical School, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
authors.forename: Henrique Rodrigues
authors.initials: HR
authors.lastname: Coelho
authors.affiliation: 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.
authors.forename: Andréia Conceição Milan Brochado
authors.initials: AC
authors.lastname: Antoniolli
authors.affiliation: 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.
authors.forename: Adilson
authors.initials: A
authors.lastname: Beatriz
authors.affiliation: 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.
authors.forename: Dênis Pires
authors.initials: DP
authors.lastname: de Lima
authors.affiliation: Postgraduate Program in Pharmacy, Center for Biological and Health Sciences, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
authors.forename: Antônio Carlos Duenhas
authors.initials: AC
authors.lastname: Monreal
authors.affiliation: Postgraduate Program in Pharmacy, Center for Biological and Health Sciences, UFMS, Campo Grande, Mato Grosso do Sul, Brazil.
authors.forename: Fabricio Garmus
authors.initials: FG
authors.lastname: Sousa
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: da Silva Gomes
authors.affiliation: 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: rodrigo.oliveira@ufms.br.
authors.forename: Rodrigo Juliano
authors.initials: RJ
authors.lastname: Oliveira
mesh_terms: D000675:Ampyrone / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D020552:Comet Assay; D003520:Cyclophosphamide / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D000675:Ampyrone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin
keywords: 4-aminoantipyrine; DNA damage; cancer; dipyrone; immunomodulatory effect