ABSTRACT
Phα1ß peptide isolated from the venom of the Phoneutria nigriventer spider has shown higher analgesic action in pre-clinical studies than ω-conotoxin MVIIA peptide used to treat severe chronic pain. In view of the great potential for the development of a new Phα1ß-based drug, a Phα1ß recombinant form (CTK 01512-2) has been studied for efficacy and safety. The aim of this study was to evaluate cytotoxic, genotoxic and mutagenic effects of a Phα1ß recombinant form and compare it with native Phα1ß and ω-conotoxin MVIIA. Cytotoxicity was evaluated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colourimetric assay in L929 mouse fibroblast cells (0.5-10.0 µmol/L). Genotoxic and mutagenic activities were analysed using the alkaline comet assay in peripheral blood and spinal cord, and the micronucleus test in bone marrow from Wistar rats treated by intrathecal injection of CTK 01512-2 (200, 500 and 1000 pmol/site), native Phα1ß (500 pmol/site) and ω-conotoxin MVIIA (200 pmol/site). CTK 01512-2 decreased the cell viability of the L929, showing IC50 of 3.3 ± 0.1 µmol/L, while the Phα1ß and ω-conotoxin MVIIA did not show cytotoxicity (IC50 > 5.0 µmol/L). Native and recombinant Phα1ß forms induced DNA damage in the spinal cord, but not in peripheral blood. CTK 01512-2 at 1000 pmol/site increased the micronucleus frequency suggesting mutagenic effects. In conclusion, the recombinant form has cytotoxic, genotoxic and mutagenic effects, evidenced in doses five times above the therapeutic dose.
Subject(s)
DNA Damage , Neurotoxins/pharmacology , Peptides/pharmacology , Spider Venoms/pharmacology , Spinal Cord/drug effects , Analgesics/pharmacology , Analgesics/toxicity , Animals , Cell Survival/drug effects , Cells, Cultured , Fibroblasts/drug effects , Inhibitory Concentration 50 , Male , Mice , Mutagenicity Tests , Mutagens , Neurotoxins/toxicity , Rats , Rats, Wistar , Spider Venoms/toxicity , omega-Conotoxins/pharmacologyABSTRACT
O Grupo Interdisciplinar e Multiprofissional n§ 11 (GIM 11), após entrar em contato e conhecer a realidade da comunidade do Jardim Bandeirantes, em Londrina, desenvolveu um trabalho de orientaçäo sobre sexualidade no Colégio Estadual Antônio Moraes de Barros, entre os alunos matriculados a partir da 5ª série. O principal objetivo do grupo era transmitir aos estudantes informaçöes básicas sobre sexualidade e suas implicaçöes, proporcionando aos mesmos a formaçäo de uma visäo crítica sobre o assunto. Outros objetivos importantes foram a composiçäo de uma equipe multiprofissional e integrada e a formaçäo de uma consciência ética e social entre os membros do grupo, surgindo daí o acadêmico com o perfil que levará ao novo modelo do profissional de saúde de que a sociedade necessita
