title: Chemoprotective effect of the tetrahydrofuran lignan grandisin in the in-vivo rodent micronucleus assay.
abstract: OBJECTIVE
  The chemoprotective effect of the tetrahydrofuran lignan grandisin against DNA damage induced by cyclophosphamide (200 mg/kg) has been evaluated using the in vitro rodent micronucleus assay.
  
  
  METHODS
  The effects of a daily oral administration of grandisin (2, 4, or 8 mg/kg) for five days before exposure to cyclophosphamide on the frequency of micronucleus in the bone marrow of normal mice exposed and unexposed to cyclophosphamide were investigated (n = 5 per group). Electrochemical measurements were applied to investigate whether the antimutagenic effects of grandisin could be, at least in part, a consequence of its or its metabolite's antioxidant properties.
  
  
  RESULTS
  Grandisin did not show mutagenic effects on the bone marrow cells of exposed mice. On the other hand, the oral administration of grandisin (2, 4, or 8 mg/kg) per day reduced dose-dependently the frequency of micronucleus, induced by cyclophosphamide, in all groups studied. Cyclic voltammograms showed two peaks for a grandisin metabolite, which were absent for grandisin.
  
  
  CONCLUSIONS
  Under the conditions tested herein, this study has shown that mice treated with grandisin presented, in a dose-dependent manner, a protective effect against cyclophosphamide-induced mutagenicity. This effect could be, at least in part, associated to grandisin bioactivation. These data open new perspectives for further investigation into the toxicology and applied pharmacology of grandisin.
authors.affiliation: Laboratório de Farmacologia e Toxicologia Celular, Universidade Federal de Goiás, UFG, Goiânia, GO, Brazil. marizecv@farmacia.ufg.br
authors.forename: Marize C
authors.initials: MC
authors.lastname: Valadares
authors.forename: Luiz Marcos
authors.initials: LM
authors.lastname: de Oliveira
authors.forename: Flávio S
authors.initials: FS
authors.lastname: de Carvalho
authors.forename: Lorenna V S
authors.initials: LV
authors.lastname: Andrade
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: dos Santos
authors.forename: Valéria
authors.initials: V
authors.lastname: de Oliveira
authors.forename: Eric de Souza
authors.initials: Ede S
authors.lastname: Gil
authors.forename: Massuo J
authors.initials: MJ
authors.lastname: Kato
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects*; D003520:Cyclophosphamide / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity
chemical_list: D005663:Furans; D017705:Lignans; D009153:Mutagens; C074346:grandisin; D003520:Cyclophosphamide