Thalia Emmanoella Sebulsqui Saraiva, Gabriela Zimmermann Prado Rodrigues, Juliana Machado Kayser, E. Dallegrave, Nathália Pulz Maus, Andriele Veiverberg, Gabriel da Costa Berna, Andriéli Carolina Schuster, Maria Gabriela de Freitas, Marina Galdino da Rocha Pitta, I. da Rocha Pitta, G. Gehlen, A. H. Betti
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引用次数: 0
Abstract
Abstract Schizophrenia is a psychiatric disorder that affects 1% of the world population and is treated with antipsychotics, which may induce important biochemical and hematological alterations. Since it is necessary to verify the safety of new molecules with antipsychotic potential, the present study aimed to evaluate the oral toxicity of PT-31, a putative α2-adrenoreceptor agonist, after acute (2000 mg/kg) and repeated doses (28 days) gavage treatment, in three different doses: minimum effective dose in animal models (10 mg/kg), twice the dose (20 mg/kg), and four times the dose (40 mg/kg), as recommended by the OECD guidelines. Balb/C female adult mice were used, and biochemical, hematological, and histopathological analyses were performed. PT-31 10 and 20 mg/kg did not cause biochemical alterations related to hepatic and renal toxicity, and neither altered glycemic and lipid profiles. The preclinical dose of PT-31 also did not promote mice histopathological changes in the liver, kidney, and brain. In the hematimetric parameters, PT-31 only increased HGB at 20 mg/kg, and MCH and MCHC at 40 mg/kg. However, all the tested doses of PT-31 showed platelet increase, which must be better investigated. Therefore, further studies are needed to investigate the safety of PT-31 as a potential antipsychotic drug.
期刊介绍:
Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy.
Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including:
In vivo studies with standard and alternative species
In vitro studies and alternative methodologies
Molecular, biochemical, and cellular techniques
Pharmacokinetics and pharmacodynamics
Mathematical modeling and computer programs
Forensic analyses
Risk assessment
Data collection and analysis.