Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Revista Brasileira de Farmacognosia (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-695X2016000100094 |
Resumo: | Abstract Prior studies demonstrate that a proteinase fraction from Vasconcellea cundinamarcensis V.M. Badillo, Caricaceae, exhibits wound healing activity in gastric and cutaneous models and antitumoral/antimetastatic effects. Here, we present the toxicity, pharmacokinetics and biodistribution data for this proteinase fraction following a single dose into Swiss mice by i.v., s.c. or p.o. routes. The i.v. and s.c. toxicity assays demonstrate that proteinase fraction at ≤20 mg/kg is non-lethal after single injection, while parental administration (p.o.) of ≤300 mg/kg does not cause death. Based on p.o. acute toxicity dose using Organisation for Economic Cooperation and Development protocols, proteinase fraction ranks as Class IV “harmful” substance. Proteinase fraction shows high uptake determined as Kp (distribution tissue/blood) in organs linked to metabolism and excretion. Also, high bioavailability (≈100%) was observed by s.c. administration. The blood contents following i.v. dose fits into a pharmacokinetic bi-compartmental model, consisting of high removal constants – kel 0.22 h−1 and kd 2.32 h−1and a half-life – t½ = 3.13 h. The Ames test of proteinase fraction (0.01–1%) demonstrates absence of mutagenic activity. Likewise, genotoxic evaluation of proteinase fraction (5 or 10 mg/kg, i.p.) shows no influence in micronuclei frequency. In conclusion, the acute doses for proteinase fraction lack mutagenic and genotoxic activity, clearing the way for clinical assays. |
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Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activityCaricaceaeCysteine proteinasesBiodistributionPharmacokineticsToxicityAbstract Prior studies demonstrate that a proteinase fraction from Vasconcellea cundinamarcensis V.M. Badillo, Caricaceae, exhibits wound healing activity in gastric and cutaneous models and antitumoral/antimetastatic effects. Here, we present the toxicity, pharmacokinetics and biodistribution data for this proteinase fraction following a single dose into Swiss mice by i.v., s.c. or p.o. routes. The i.v. and s.c. toxicity assays demonstrate that proteinase fraction at ≤20 mg/kg is non-lethal after single injection, while parental administration (p.o.) of ≤300 mg/kg does not cause death. Based on p.o. acute toxicity dose using Organisation for Economic Cooperation and Development protocols, proteinase fraction ranks as Class IV “harmful” substance. Proteinase fraction shows high uptake determined as Kp (distribution tissue/blood) in organs linked to metabolism and excretion. Also, high bioavailability (≈100%) was observed by s.c. administration. The blood contents following i.v. dose fits into a pharmacokinetic bi-compartmental model, consisting of high removal constants – kel 0.22 h−1 and kd 2.32 h−1and a half-life – t½ = 3.13 h. The Ames test of proteinase fraction (0.01–1%) demonstrates absence of mutagenic activity. Likewise, genotoxic evaluation of proteinase fraction (5 or 10 mg/kg, i.p.) shows no influence in micronuclei frequency. In conclusion, the acute doses for proteinase fraction lack mutagenic and genotoxic activity, clearing the way for clinical assays.Sociedade Brasileira de Farmacognosia2016-02-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-695X2016000100094Revista Brasileira de Farmacognosia v.26 n.1 2016reponame:Revista Brasileira de Farmacognosia (Online)instname:Sociedade Brasileira de Farmacognosia (SBFgnosia)instacron:SBFGNOSIA10.1016/j.bjp.2015.09.008info:eu-repo/semantics/openAccessLemos,Fernanda O.Villalba,Maria Imaculada C.Tagliati,Carlos A.Cardoso,Valbert N.Salas,Carlos E.Lopes,Miriam T.P.eng2016-02-03T00:00:00Zoai:scielo:S0102-695X2016000100094Revistahttp://www.sbfgnosia.org.br/revista/https://old.scielo.br/oai/scielo-oai.phprbgnosia@ltf.ufpb.br1981-528X0102-695Xopendoar:2016-02-03T00:00Revista Brasileira de Farmacognosia (Online) - Sociedade Brasileira de Farmacognosia (SBFgnosia)false |
dc.title.none.fl_str_mv |
Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity |
title |
Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity |
spellingShingle |
Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity Lemos,Fernanda O. Caricaceae Cysteine proteinases Biodistribution Pharmacokinetics Toxicity |
title_short |
Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity |
title_full |
Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity |
title_fullStr |
Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity |
title_full_unstemmed |
Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity |
title_sort |
Biodistribution, pharmacokinetics and toxicity of a Vasconcellea cundinamarcensis proteinase fraction with pharmacological activity |
author |
Lemos,Fernanda O. |
author_facet |
Lemos,Fernanda O. Villalba,Maria Imaculada C. Tagliati,Carlos A. Cardoso,Valbert N. Salas,Carlos E. Lopes,Miriam T.P. |
author_role |
author |
author2 |
Villalba,Maria Imaculada C. Tagliati,Carlos A. Cardoso,Valbert N. Salas,Carlos E. Lopes,Miriam T.P. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Lemos,Fernanda O. Villalba,Maria Imaculada C. Tagliati,Carlos A. Cardoso,Valbert N. Salas,Carlos E. Lopes,Miriam T.P. |
dc.subject.por.fl_str_mv |
Caricaceae Cysteine proteinases Biodistribution Pharmacokinetics Toxicity |
topic |
Caricaceae Cysteine proteinases Biodistribution Pharmacokinetics Toxicity |
description |
Abstract Prior studies demonstrate that a proteinase fraction from Vasconcellea cundinamarcensis V.M. Badillo, Caricaceae, exhibits wound healing activity in gastric and cutaneous models and antitumoral/antimetastatic effects. Here, we present the toxicity, pharmacokinetics and biodistribution data for this proteinase fraction following a single dose into Swiss mice by i.v., s.c. or p.o. routes. The i.v. and s.c. toxicity assays demonstrate that proteinase fraction at ≤20 mg/kg is non-lethal after single injection, while parental administration (p.o.) of ≤300 mg/kg does not cause death. Based on p.o. acute toxicity dose using Organisation for Economic Cooperation and Development protocols, proteinase fraction ranks as Class IV “harmful” substance. Proteinase fraction shows high uptake determined as Kp (distribution tissue/blood) in organs linked to metabolism and excretion. Also, high bioavailability (≈100%) was observed by s.c. administration. The blood contents following i.v. dose fits into a pharmacokinetic bi-compartmental model, consisting of high removal constants – kel 0.22 h−1 and kd 2.32 h−1and a half-life – t½ = 3.13 h. The Ames test of proteinase fraction (0.01–1%) demonstrates absence of mutagenic activity. Likewise, genotoxic evaluation of proteinase fraction (5 or 10 mg/kg, i.p.) shows no influence in micronuclei frequency. In conclusion, the acute doses for proteinase fraction lack mutagenic and genotoxic activity, clearing the way for clinical assays. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-02-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-695X2016000100094 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-695X2016000100094 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1016/j.bjp.2015.09.008 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Farmacognosia |
publisher.none.fl_str_mv |
Sociedade Brasileira de Farmacognosia |
dc.source.none.fl_str_mv |
Revista Brasileira de Farmacognosia v.26 n.1 2016 reponame:Revista Brasileira de Farmacognosia (Online) instname:Sociedade Brasileira de Farmacognosia (SBFgnosia) instacron:SBFGNOSIA |
instname_str |
Sociedade Brasileira de Farmacognosia (SBFgnosia) |
instacron_str |
SBFGNOSIA |
institution |
SBFGNOSIA |
reponame_str |
Revista Brasileira de Farmacognosia (Online) |
collection |
Revista Brasileira de Farmacognosia (Online) |
repository.name.fl_str_mv |
Revista Brasileira de Farmacognosia (Online) - Sociedade Brasileira de Farmacognosia (SBFgnosia) |
repository.mail.fl_str_mv |
rbgnosia@ltf.ufpb.br |
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1752122469691424768 |