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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Amino Acids; v. 50, n. 2, p. 267-278, FEB 2018.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 15/08812-0 - Caracterização do(s) mecanismo(s) molecular(es) envolvidos no efeito miotóxico da crotamina, uma toxina da peçonha da cascavel com potencial emprego teranóstico
• Beneficiário: Lucas de Carvalho Porta
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/13392-4 - Avaliação do uso dos análogos da crotamina em diagnóstico ou terapia
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/02413-1 - Validação da crotamina como biomarcador e avaliação do seu potencial uso na terapia de doenças humanas
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular