Oral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile

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dc.citation.issue2
dc.citation.volume50
dc.contributor.authorCampeiro, Joana D. [UNIFESP]
dc.contributor.authorMarinovic, Marcelo P. [UNIFESP]
dc.contributor.authorCarapeto, Fernando Cintra [UNIFESP]
dc.contributor.authorDal Mas, Caroline [UNIFESP]
dc.contributor.authorMonte, Gabriela Guilherme [UNIFESP]
dc.contributor.authorPorta, Lucas Carvalho [UNIFESP]
dc.contributor.authorNering, Marcela B. [UNIFESP]
dc.contributor.authorOliveira, Eduardo B.
dc.contributor.authorHayashi, Mirian A. F. [UNIFESP]
dc.coverageWien
dc.date.accessioned2020-07-08T13:09:49Z
dc.date.available2020-07-08T13:09:49Z
dc.date.issued2018
dc.description.abstractThe efficacy of crotamine as antitumoral was first demonstrated by daily intraperitoneal (IP) injections of low doses of this toxin in an animal model bearing melanoma tumors. Significant inhibition of tumor growth and increased lifespan of mice bearing tumor was also noticed after 21 consecutive days of this daily IP administration of crotamine. However, due to the limited acceptance of treatments by IP route in clinical conditions, herein, we evaluated the antitumor effect of this native polypeptide employing the oral route. The efficacy of crotamine in inhibiting the melanoma growth in vivo, even after passing through the gastrointestinal tract of the animal, was confirmed here. In addition, biochemical biomarkers and also histopathological analysis showed both the absence of any potential toxic effects in tissues or organs of the animal in which the highest accumulation of crotamine is expected. Interestingly, a reduction of weight gain was observed mainly in animals with tumor treated with crotamine by IP route, but not by oral administration. Albeit, oral administered crotamine was able to significantly decrease the body weight gain of healthy animals without tumor. Taking advantage of this same experimental animal models receiving crotamine by oral route, it was possible to show metabolic changes as the increased capacity of glucose clearance, which was accompanied by a reduction of the total cholesterol, and by increased high-density lipoprotein levels, both observed mainly in the absence of tumor. Triglycerides and low-density lipoprotein were also significantly decreased, but only in the absence of tumor. Taken together, these data suggest a clear trend for metabolic positive effects and mischaracterize unhealthy condition of animals, with or without tumors, treated with crotamine for 21 days. In addition, this study confirmed the efficacy of crotamine administered by oral route as antitumor agent, which besides the additional advantage of administration convenience and decreased risk of toxic effects, allowed the serendipitous observation of several positive metabolic effects on treated animals.en
dc.description.affiliationUniv Fed Sao Paulo UNIFESP, EPM, Dept Farmacol, Rua 3 Maio 100,Ed INFAR,3rd Floor, BR-04044020 Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo UNIFESP, EPM, Dept Patol, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo USP RP, Dept Bioquim & Imunol, Ribeirao Preto, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP, EPM, Dept Farmacol, Rua 3 Maio 100,Ed INFAR,3rd Floor, BR-04044020 Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP, EPM, Dept Patol, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP)
dc.description.sponsorshipNational Council of Technological and Scientific Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq)
dc.description.sponsorshipCAPES
dc.description.sponsorshipCNPq
dc.description.sponsorshipIDFAPESP: 2013/13392-4, 2017/02413-1, 2015/08812-0
dc.description.sponsorshipIDCNPq: 311815/2012-0, 475739/2013-2, 39337/2016-0
dc.format.extent267-278
dc.identifierhttp://dx.doi.org/10.1007/s00726-017-2513-3
dc.identifier.citationAmino Acids. Wien, v. 50, n. 2, p. 267-278, 2018.
dc.identifier.doi10.1007/s00726-017-2513-3
dc.identifier.issn0939-4451
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54231
dc.identifier.wosWOS:000422850200006
dc.language.isoeng
dc.publisherSpringer Wien
dc.relation.ispartofAmino Acids
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectCrotamineen
dc.subjectSnake toxinen
dc.subjectMelanoma tumoren
dc.subjectMetabolismen
dc.subjectOral administrationen
dc.titleOral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profileen
dc.typeinfo:eu-repo/semantics/article
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