Atividade anti-tumoral e imunomodulatória de complexos de paládio (II) utilizando modelo experimental de Ehrlich

O câncer, manifestação originada pelo crescimento descontrolado de células, afeta milhões de indivíduos. Os macrófagos são as primeiras células a serem ativadas para participar de uma resposta imunológica propriamente dita, são células capazes de secretar mais de cem produtos biologicamente ativos, entre esses, espécies reativas de nitrogênio e citocinas que atuam no contexto da resposta imunológica e/ou inflamatória. Sabendo que compostos de paládio (II) podem apresentar potenciais atividades anti - tumorais, neste trabalho foram testado os compostos de fórmula geral [Pd(dmba)(Cl)tu] e [Pd(dmba)(N3)tu], nos quais dmba = N,N-dimetilbenzilamina e tu = tiouréia quanto a atividade antiinflamatória, antitumoral e mutagênica dos mesmos.Como droga padrão das reações realizadas foi utilizada a cis-platina. Foi determinada a ação destes compostos frente ao sistema imunológico através, de ensaios de determinação de citotoxicidade mediano (IC50) pela técnica de MTT, óxido nítrico (NO), peróxido de hidrogênio (H2O2), determinação das citocinas IL-1, IL-6, IL-12, TNF-α e IL-10. Além disso, foi determinado a atividade antitumoral dos compostos frente à célula tumoral de Ehrlich, assim como a atividade mutagênica pelo teste de Ames e Ensaio com plasmídio pUC 9.1. Os resultados mostraram produção de NO e das citocinas IL-1, IL-6, IL-12 e TNF-α; moderada produção de H2O2 pelos macrófagos peritoneais de animais normais e animais portadores do tumor de Ehrlich na sua forma sólida, estimulados com os compostos e seus ligantes, assim como a cis-platina. Por outro lado, de maneira contrária às outras citocinas testadas, não houve a produção de IL-10. No que se refere à atividade antitumoral dos compostos testados, estes mostraram efeito citotóxico sobre a linhagen tumoral testada. Com relação à atividade mutagênica, os compostos...The cancer, manifestation originated by the growth not controlled of cells, affects million of individuals. Macrophages are the first cells to be activated to participate in an immune response itself, are cells to able to secreting more than one hundred biologically active products, among these, reactive nitrogen species and cytokines that act in the context of the immune response and / or inflammatory. Knowing that compounds of palladium (II) can be potential activities anti - tumor in this study was tested compounds of general formula [Pd (Pd) (Cl) tu] and [Pd (Pd) (N3) tu], where Pd = N, N-dimetilbenzilamina and tu = thiourea as the anti-inflammatory, antitumor and mutagenic of the same. As standard was used the cis-platinum. We determining the action of these compounds against the immune system, for tests to determine the median cytotoxicity (IC50) by the MTT technique, nitric oxide (NO), hydrogen peroxide (H2O2), determination of IL-1, IL-6 , IL-12, TNF-α and IL-10. Moreover, it was determined the antitumor activity of compounds against the Ehrlich tumor cell, as well as mutagenic by the Ames test and test with plasmid pUC 9.1. The results showed NO production and the IL-1, IL-6, IL-12 and TNF-α, by peritoneal macrophages from normal animals and animals with Ehrlich tumor in solid form was stimulated by the compounds and their ligands as well as cis-platinum. Moreover, in contrary manner to other cytokines tested, there wasn’t production of IL-10, and H2O2. With regard to the antitumor activity of the compounds tested, these showed cytotoxic effect on tumor lineage tested. With respect to mutagenic activity, compounds and ligands weren’t mutagenic in vitro, unlike cis-platinum was shown to be mutagenic, causing mutations in the DNA of Salmonella typhimurium by the Ames test. The compounds and ligants were not also to induce DNA breaks in the plasmid... (Complete abstract click electronic access below)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

The role of qualea multiflora on mammary tumour cells and immune system

Species of the genus Qualea are used by the Brazilian public as a natural anti-inflammatory. Based on this evidence, we evaluated the effects of terpene fractions (βF and TF) obtained from Qualea multiflora on nitric oxide production (Griess assay), cytokines (IL-1, IL-10, IL-12, and TNF-a) and the transcription factor NF-κB by peritoneal macrophages. Since there is a relationship between inflammation and cancer, the cytotoxicity of βF and TF against mammary tumoural cell lineage, and macrophages was evaluated. Inhibition levels close to 90% of the production of NO, IL-1, IL-12 and TNF-a; about 32% of NF-κB; and a large stimulation of IL-10 production (close to the positive control) by peritoneal macrophages were observed in response to βF and TF which are correlated with anti-inflammatory activity. Additionally, the samples showed exceptional cytotoxic activity against tumoural cells but not against macrophages. Since anti-inflammatory activity is important in tumour inhibition, further examination of potential anti-cancerous activity of Qualea multiflora is warranted

Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate

Methyl dihydrojasmonate (MJ) has been studied because of its application as an antitumor drug compound. However, as MJ is a poorly water-soluble compound, a suitable oil-in-water microemulsion (ME) has been studied in order to provide its solubilization in an aqueous media and to allow its administration by the parenteral route. The ME used in this work was characterized on the pseudo-ternary phase diagram by dynamic light scattering and rheological measurements. Regardless of the drug presence, the droplet size was directly dependent on the oil/surfactant (O/S) ratio. Furthermore, the drug incorporation into the ME significantly increased the ME diameter, mainly at low O/S ratios. The rheological evaluation of the systems showed that in the absence of drug a Newtonian behavior was observed. On the other hand, in the presence of MJ the ME systems revealed pseudoplastic behavior, independently of the O/S ratio. The in vivo studies demonstrated that not only was the effect on the tumor inhibition inversely dependent on the MJ-loaded ME administered dose, but also it was slightly higher than the doxorubicin alone, which was used as the positive control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found at doses in which it possesses antitumor activity. MJ revealed to be nontoxic at doses higher than 350 mg/kg, which was higher than the dose that provides tumor-inhibition effect in this study. Because the MJ-loaded ME was shown to have anticancer activity comparable to doxorubicin, the ME described here may be considered a suitable vehicle for parenteral administration of MJ.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq