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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