title: A new synthetic resorcinolic lipid 3-heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one: evaluation of toxicology and ability to potentiate the mutagenic and apoptotic effects of cyclophosphamide.
abstract: Resorcinolic lipids have important biological actions, including anti-carcinogenic activity. Therefore, we evaluated the mutagenic, genotoxic, immunomodulatory and apoptotic potential and the biochemical and histopathological changes caused by the synthetic resorcinolic lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one, (AMS35AA; 10, 20 and 40 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg) in Swiss mice. The results indicated that AMS35AA is not genotoxic or mutagenic and does not alter liver or kidney histology. However, the compound does cause an increase (p < 0.05) in the levels of glutamic-oxaloacetic transaminase and creatinine and in splenic phagocytosis and liver and kidney apoptosis. When combined with cyclophosphamide, AMS35AA caused increased (p < 0.05) mutagenic damage (although the compound had anti-genotoxic activity), splenic phagocytosis, neutropenia and glutamic-oxaloacetic transaminase and creatinine levels (even in the absence of histological damage) and induced liver and kidney apoptosis. We conclude that this resorcinolic lipid may be an important chemotherapy adjuvant that can potentiate mutagenic damage and increase apoptosis caused by cyclophosphamide without causing adverse effects. In addition, the immunomodulatory activity of the compound should be noted, which counters reductions in lymphocyte number, a primary side effect of cyclophosphamide in cancer therapy.
authors: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Núcleo de Hospital Universitário - NHU, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil; Programa de Mestrado em Farmácia, Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil.
authors: Stephanie Dynczuki
authors: SD
authors: Navarro
authors: Programa de Mestrado em Farmácia, Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil; Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil.
authors: Adilson
authors: A
authors: Beatriz
authors: Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil.
authors: Alisson
authors: A
authors: Meza
authors: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Núcleo de Hospital Universitário - NHU, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil; Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina "Dr. Hélio Mandetta" - FAMED, Campo Grande, MS, Brazil.
authors: João Renato
authors: JR
authors: Pesarini
authors: Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil.
authors: Roberto da Silva
authors: Rda S
authors: Gomes
authors: Instituto de Química, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil.
authors: Caroline Bilhar
authors: CB
authors: Karaziack
authors: Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil.
authors: Andréa Luiza
authors: AL
authors: Cunha-Laura
authors: Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil.
authors: Antônio Carlos Duenhas
authors: AC
authors: Monreal
authors: Departamento de Química, Universidade Federal do Espírito Santo - UFES, Vitória, ES, Brazil.
authors: Wanderson
authors: W
authors: Romão
authors: Departamento de Química, Universidade Federal do Espírito Santo - UFES, Vitória, ES, Brazil.
authors: Valdemar
authors: V
authors: Lacerda Júnior
authors: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Núcleo de Hospital Universitário - NHU, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil; Programa de Doutorado em Biotecnologia e Biodiversidade - Rede Pró Centro-Oeste, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil.
authors: Mariana de Oliveira
authors: Mde O
authors: Mauro
authors: Centro de Estudos em Células Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Núcleo de Hospital Universitário - NHU, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil; Programa de Mestrado em Farmácia, Centro de Ciências Biológicas e da Saúde - CCBS, Universidade Federal de Mato Grosso do Sul - UFMS, Campo Grande, MS, Brazil; Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Faculdade de Medicina "Dr. Hélio Mandetta" - FAMED, Campo Grande, MS, Brazil. Electronic address: rodrigo.oliveira@ufms.br.
authors: Rodrigo Juliano
authors: RJ
authors: Oliveira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D020552:Comet Assay; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008055:Lipids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009153:Mutagens / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D012118:Resorcinols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D008055:Lipids; D009153:Mutagens; D012118:Resorcinols; D003520:Cyclophosphamide
keywords: Chemotherapy; Comet assay; Cytosporone; Immunomodulation; Micronucleus