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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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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Author(s):
Campeiro, Joana D. [1] ; Marinovic, Marcelo P. [1] ; Carapeto, Fernando Cintra [2] ; Dal Mas, Caroline [1] ; Monte, Gabriela Guilherme [1] ; Porta, Lucas Carvalho [1] ; Nering, Marcela B. [1] ; Oliveira, Eduardo B. [3] ; Hayashi, Mirian A. F. [1]
Total Authors: 9
Affiliation:
[1] Univ Fed Sao Paulo UNIFESP, EPM, Dept Farmacol, Rua 3 Maio 100, Ed INFAR, 3rd Floor, BR-04044020 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo UNIFESP, EPM, Dept Patol, Sao Paulo - Brazil
[3] Univ Sao Paulo USP RP, Dept Bioquim & Imunol, Ribeirao Preto - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Amino Acids; v. 50, n. 2, p. 267-278, FEB 2018.
Web of Science Citations: 3
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. (AU)

FAPESP's process: 15/08812-0 - Characterization of mechanism(s) molecular(s) involved in myotoxic effect of crotamine, a toxin from the venom of rattlesnake with potential teranostic employment
Grantee:Lucas de Carvalho Porta
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/13392-4 - Evaluation of the use of analogs of crotamine for diagnosis or therapy
Grantee:Mirian Akemi Furuie Hayashi
Support Opportunities: Regular Research Grants
FAPESP's process: 17/02413-1 - Validation of crotamine as a biomarker and evaluation of its potential use in the therapy of human diseases
Grantee:Mirian Akemi Furuie Hayashi
Support Opportunities: Regular Research Grants