Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity
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. D...
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doaj-10194f3bcbaf480f88ffcab08a20c7d62020-11-25T01:55:53ZengElsevierToxicology Reports2214-75002019-01-0165163Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activityDurvanei A. Maria0Sonia Elisabete A.L. Will1Rosemary V. Bosch2Jean G. Souza3Juliana M. Sciani4Mauricio B. Goldfeder5Giuliana G. Rondon6Ana M. Chudzinski-Tavassi7Laboratório de Biologia Molecular, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, BrazilLaboratório de Biologia Molecular, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, BrazilLaboratório de Biologia Molecular, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, BrazilLaboratório de Biologia Molecular, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, BrazilLaboratório de Biologia Molecular, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, BrazilLaboratório de Biologia Molecular, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, BrazilLaboratório de Biologia Molecular, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, BrazilCorresponding author.; Laboratório de Biologia Molecular, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, 05503-900, SP, BrazilAmblyomin-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. Keywords: Amblyomin-X, Kunitz-type inhibitor, Toxicity, Preclinicalhttp://www.sciencedirect.com/science/article/pii/S2214750018305468 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Durvanei A. Maria Sonia Elisabete A.L. Will Rosemary V. Bosch Jean G. Souza Juliana M. Sciani Mauricio B. Goldfeder Giuliana G. Rondon Ana M. Chudzinski-Tavassi |
spellingShingle |
Durvanei A. Maria Sonia Elisabete A.L. Will Rosemary V. Bosch Jean G. Souza Juliana M. Sciani Mauricio B. Goldfeder Giuliana G. Rondon Ana M. Chudzinski-Tavassi Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity Toxicology Reports |
author_facet |
Durvanei A. Maria Sonia Elisabete A.L. Will Rosemary V. Bosch Jean G. Souza Juliana M. Sciani Mauricio B. Goldfeder Giuliana G. Rondon Ana M. Chudzinski-Tavassi |
author_sort |
Durvanei A. Maria |
title |
Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity |
title_short |
Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity |
title_full |
Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity |
title_fullStr |
Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity |
title_full_unstemmed |
Preclinical evaluation of Amblyomin-X, a Kunitz-type protease inhibitor with antitumor activity |
title_sort |
preclinical evaluation of amblyomin-x, a kunitz-type protease inhibitor with antitumor activity |
publisher |
Elsevier |
series |
Toxicology Reports |
issn |
2214-7500 |
publishDate |
2019-01-01 |
description |
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. Keywords: Amblyomin-X, Kunitz-type inhibitor, Toxicity, Preclinical |
url |
http://www.sciencedirect.com/science/article/pii/S2214750018305468 |
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