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Drug Delivery Letters

Editor-in-Chief

ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

Letter Article

Genotoxic and Mutagenic Assessment of PT-31, a Molecule with Antipsychotic Potential

Author(s): Cassiana Bigolin, Andriele Veiverberg, Gabriela Zimmermann Prado Rodrigues*, Ana Letícia Hilario Garcia, Juliana Machado Kayser, Fernando Bertoldi, Marcelo Dutra Arbo, Marina Galdino Pitta, Ivan da Rocha Pitta, Günther Gehlen and Andresa Heemann Betti

Volume 13, Issue 4, 2023

Published on: 23 June, 2023

Page: [322 - 328] Pages: 7

DOI: 10.2174/2210303113666230607151339

Price: $65

Abstract

The PT-31 molecule, a potential antipsychotic, has demonstrated promising results when orally administrated to in vivo models. A recent study suggested the genotoxic and mutagenic potential of PT-31 after acute treatment by intraperitoneal route. This study aimed to evaluate PT-31 potential of inducing genotoxic or mutagenic damage after acute oral administration. For that, adult males and females Balb/C mice were treated acutely by oral administration with vehicle or PT-31 in three different doses (10, 20, and 40 mg kg-1). After 24 hours from PT-31 administration, animals were euthanized for performing the comet and micronucleus assays. None of the tested groups of PT-31 presented a significant increase in damage index and MN frequency. However, they presented the following tendency on damage index: females presented a tendency at 40 mg kg-1 and males at 20 mg kg-1. Regarding the MN assay, male mice at the highest dose of 40 mg kg-1 presented a tendency of increased MN frequency. Also, there was a significant increase in PCE/NCE ratio in male mice. Results suggest that the male mice group presented higher susceptibility to damage. The tendency of increased damage to DNA and MN frequency suggests that the molecule PT-31 may induce reparable damage to DNA, and these DNA strand repairs may have originated from the MN. However, significant genotoxic and mutagenic effects were not observed. This study reinforces the atypical profile of the molecule as much as its safety by oral route administration.

Keywords: Antipsychotic, comet assay, micronucleus test, schizophrenia, Balb/C, bone marrow.

Graphical Abstract
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