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

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

Author Campeiro, Joana D. Autor UNIFESP Google Scholar
Marinovic, Marcelo P. Autor UNIFESP Google Scholar
Carapeto, Fernando Cintra Autor UNIFESP Google Scholar
Dal Mas, Caroline Autor UNIFESP Google Scholar
Monte, Gabriela Guilherme Autor UNIFESP Google Scholar
Porta, Lucas Carvalho Autor UNIFESP Google Scholar
Nering, Marcela B. Autor UNIFESP Google Scholar
Oliveira, Eduardo B. Google Scholar
Hayashi, Mirian A. F. Autor UNIFESP Google Scholar
Abstract The 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.
Keywords Crotamine
Snake toxin
Melanoma tumor
Metabolism
Oral administration
xmlui.dri2xhtml.METS-1.0.item-coverage Wien
Language English
Sponsor Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP)
National Council of Technological and Scientific Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq)
CAPES
CNPq
Grant number FAPESP: 2013/13392-4, 2017/02413-1, 2015/08812-0
CNPq: 311815/2012-0, 475739/2013-2, 39337/2016-0
Date 2018
Published in Amino Acids. Wien, v. 50, n. 2, p. 267-278, 2018.
ISSN 0939-4451 (Sherpa/Romeo, impact factor)
Publisher Springer Wien
Extent 267-278
Origin http://dx.doi.org/10.1007/s00726-017-2513-3
Access rights Closed access
Type Article
Web of Science ID WOS:000422850200006
URI https://repositorio.unifesp.br/handle/11600/54231

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