Genotoxic and Mutagenic Activity of PT-31

Title:Genotoxic and Mutagenic Activity of PT-31

Volume: 17 Issue: 12

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 and Ana A.C. Melo-Cavalcante

Affiliation:

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

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.

Cite this article as:

Neto P.L. Manoel, Gomes C.V. Débora, Júnior L.G. Antonio, Paz F.C.J. Márcia, Alencar V.O.B. Marcus, Islam T. Md., Ferreira M.P. Paulo and Melo-Cavalcante A.C. Ana, Genotoxic and Mutagenic Activity of PT-31, Current Pharmaceutical Biotechnology 2016; 17 (12) . https://dx.doi.org/10.2174/1389201017666160811122811