Chemoprotective effect of the tetrahydrofuran lignan grandisin in the in-vivo rodent micronucleus assay
Corresponding Author
Marize C. Valadares
Laboratório de Farmacologia e Toxicologia Celular
Marize Campos Valadares, Faculdade de Farmácia – UFG, Praça Universitária esquina com 1a Avenida s/n, Setor Universitário, 74605-220, Goiânia, GO, Brazil. E-mail: [email protected]Search for more papers by this authorLuiz Marcos de Oliveira Júnior
Laboratório de Farmacologia e Toxicologia Celular
Search for more papers by this authorFlávio S. de Carvalho
Laboratório de Farmacologia e Toxicologia Celular
Search for more papers by this authorLorenna V.S. Andrade
Laboratório de Farmacologia e Toxicologia Celular
Search for more papers by this authorAlexandre P. dos Santos
Laboratório de Farmacologia e Toxicologia Celular
Search for more papers by this authorEric de Souza Gil
Laboratório de Análise Farmacêutica e Ambiental, Faculdade de Farmácia, Universidade Federal de Goiás, UFG, Goiânia, GO
Search for more papers by this authorMassuo J. Kato
Laboratório de Química de Produtos Naturais, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil
Search for more papers by this authorCorresponding Author
Marize C. Valadares
Laboratório de Farmacologia e Toxicologia Celular
Marize Campos Valadares, Faculdade de Farmácia – UFG, Praça Universitária esquina com 1a Avenida s/n, Setor Universitário, 74605-220, Goiânia, GO, Brazil. E-mail: [email protected]Search for more papers by this authorLuiz Marcos de Oliveira Júnior
Laboratório de Farmacologia e Toxicologia Celular
Search for more papers by this authorFlávio S. de Carvalho
Laboratório de Farmacologia e Toxicologia Celular
Search for more papers by this authorLorenna V.S. Andrade
Laboratório de Farmacologia e Toxicologia Celular
Search for more papers by this authorAlexandre P. dos Santos
Laboratório de Farmacologia e Toxicologia Celular
Search for more papers by this authorEric de Souza Gil
Laboratório de Análise Farmacêutica e Ambiental, Faculdade de Farmácia, Universidade Federal de Goiás, UFG, Goiânia, GO
Search for more papers by this authorMassuo J. Kato
Laboratório de Química de Produtos Naturais, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil
Search for more papers by this authorAbstract
Objectives 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.
Key findings 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.
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