Genotoxic and Mutagenic Activity of PT-31

Author(s): Manoel P.L. Neto, Débora C.V. Gomes, Antonio L.G. Júnior, Márcia F.C.J. Paz, Marcus V.O.B. Alencar, Md. T. Islam, Paulo M.P. Ferreira, Ana A.C. Melo-Cavalcante.

Journal Name: Current Pharmaceutical Biotechnology

Volume 17 , Issue 12 , 2016

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Abstract:

Toxicity assessment is an important tool in drug discovery and development. PT-31 (3-(2-chloro-6-fluorobenzyl)-imidazolidine-2,4-dione) is an imidazolidine- 2,4-dione analogue of clonidine that displays a dose-dependent analgesic profile and synergism with morphine. This study investigated genotoxic and mutagenic effects of PT-31 in Swiss mice. For this, ten mice (M1:F1) per group were treated with PT-31 intraperitoneally (i.p.) at 0.5, 1.0 and 5.0 mg/kg. The dimethyl sulfoxide (0.5%) and 50 mg/kg cyclophosphamide (i.p.) were taken as negative (NC) and positive controls, respectively. The bone marrow cells were collected after 24 h, while peripheral blood after 30 min, 12 h and 24 h of the treatment for the comet assay. Micronucleus (MN) test was performed only on bone marrow cells collected after 24 h of i.p. treated animals. A hundred cells were considered for the comet assay and quantification of the index of damage and frequency of damage. Lack of genotoxicity with 0.5 mg/kg of PT-31 and DNA repair ability with 0.5 and 1.0 mg/kg doses at 12 h and 24 h in comparison to NC group was observed (P<0.05). There was an increase in MN formation by PT-31 1.0 and 5.0 mg/kg treated female and male mice, respectively. PT-31 induced genotoxic and mutagenic effects only in higher doses.

Keywords: Genotoxicity, imidazolidine, in vivo, mutagenicity, Mus musculus, PT-31.

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Article Details

VOLUME: 17
ISSUE: 12
Year: 2016
Page: [1043 - 1048]
Pages: 6
DOI: 10.2174/1389201017666160811122811
Price: $58

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