Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity. (2019)

• Record Type: Journal Article
• Authors: Maria, Durvanei A.; Will, Sonia Elisabete A.L.; Bosch, Rosemary V.; Souza, Jean G.; Sciani, Juliana M.; Goldfeder, Mauricio B.; Rondon, Giuliana G.; Chudzinski-Tavassi, Ana M.
• Is Part Of: Toxicology reports. Volume 6(2019)
• Page Start: 51
• Page End: 63
• Publication Date: 2019
• Subjects: Amblyomin-X -- Kunitz-type inhibitor -- Toxicity -- Preclinical; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2018.11.014
• Languages: English
• ISSNs: 2214-7500

Abstract

Graphical abstract: Highlights: Amblyomin-X is a recombinant protein with selective antitumor activity, causing tumor reduction in vivo. Acute and subchronic toxicity studies shows low toxicity in healthy mice, with reversible adverse effects. Amblyomin-X toxicity profile was defined. 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.