Utilização do ensaio da membrana cório-alantoide (HET-CAM) para análise do efeito irritante de complexos de rutênio

Abstract

Even though metallopharmaceuticals are part of a small niche the metallopharmaceuticals have been gaining prominence due to their potential pharmacological use as nitric oxide donors (NO) in cardiovascular disease, kidney disease, and even glaucoma. Ruthenium complex act directly in the NO parthway acting on second messengers for vasodilatory action. Given this potencial drug it is important carry out toxicological studies, ensuring the safety of the drug and that its action is only therapeutic. Many of these toxicity studies are performed on animals, counteracting the global trend of decrease the use of animals in laboratory testing. The purpose of this study was to evaluate the toxiconological effects of five ruthenium complexes (FOR011A FOR811A, FOR711A, FOR011B e FOR811B) using in vitro methodology of Hen’s Eggs Test Chorioallantoic Membrane (HET-CAM) and to evaluate cell viability in the strain of LLC-MK2 cells from monkey proximal tubule renal cell line (Macaca mulata) by cell viability testing using the 3- (4,5-dimethylthiazol-2yl) -2,5- bromide salt reduction reaction diphenyl tetrazolium (MTT). The tests showed that the ruthenium complexes tested showed no irritant potential, but there is cytotoxicity. FOR011B showed cytotoxicity at concentrations 12.5; 25; 50 and 100 µM while the FOR011A and FOR711A complexes only at concentrations of 25; 50 and 100 µM. Despite the present cytotoxic effect, cell viability remained above 70%. The HET-CAM assay, together with cell viability by MTT assay were important to assess the toxicological potential of the complexes. Further studies will be performed, this time starting from the data obtained in this study for in vivo assays.