Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity
Toxicol Rep, v. 6, p. 51-63, 2019
Artículo
en Inglés
| Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP
| ID: bud-2630
Biblioteca responsable:
BR78.1
ABSTRACT
Amblyomin-X, a Kunitz-type protease inhibitor, is a recombinant protein that selectively induces apoptosis in tumor cells and promotes tumor reduction in vivo in melanoma animal models. Furthermore, Amblyomin-X was able to drastically reduce lung metastasis in a mice orthotopic kidney tumor model. Due to its antitumor activity, Amblyomin-X potential to become a new drug is currently under investigation, therefore the aim of the present study was to perform preclinical assays to evaluate Amblyomin-X toxicity in healthy mice. Exploratory toxicity assays have shown that treatment with 512?mg/kg of Amblyomin-X lead to animal mortality, therefore two groups of treatment were evaluated in the present work in the acute toxicity assay, animals were injected once with doses ranging from 4 to 256?mg/kg of Amblyomin-X, while in the subacute toxicity assay, animals were injected with 0.25, 0.57 and 1?mg/kg of Amblyomin-X daily, during 28 days. Following this treatment regimens, Amblyomin-X did not cause any mortality; moreover, toxicity signs were discrete, reversible and observed only at the higher doses, thus establishing a safety profile for administration in mice, which can be further used to determine the dose translation of this novel drug candidate for treatment in other species.
Texto completo:
Disponible
Colección:
Bases de datos nacionales
/
Brasil
Base de datos:
Sec. Est. Saúde SP
/
SESSP-IBPROD
Idioma:
Inglés
Revista:
Toxicol Rep
Año:
2019
Tipo del documento:
Artículo