Efeitos renais dos metalofármacos FOR011B e FOR811B em modelos de rim isolado de rato e isquemia/reperfusão (I/R) celular

Abstract

The renal system through multiple actions exerts homeostasis of the body. Several complications cause damage and damage the structure and also decrease the functional activity of the kidneys, triggering a clinical condition called Acute Renal Injury (AKI). Compounds containing metal ions are used with great relevance in the treatment of different diseases. In the last years, the chemistry of nitrosyl metal complexes has become significant due to the important role involving transition metal in the biological processes of NO. This paper aims to study the renal effects of FOR011B and FOR811B metallopharmaceuticals in isolated rat kidney and cellular Ischemia / Reperfusion (I / R) models. The experiments to evaluate renal hemodynamic effects were performed with kidney isolated from Wistar rats and biochemical measurements of the collected samples were performed and quantification of cGMP by ELISA. I/R model in vitro were performed in LLC-MK2 renal tubule cells line and cell respiration assay by flow cytometry through the analysis of mitochondrial transmembrane potential with Rhodamine 123 dye. The project was approved by the Ethics Committee on Use of Animals (CEUA)/UFC under protocol number 102/2016. In compound kidney infusion compound FOR011B caused increased perfusion pressure and renal vascular resistance. The FOR011B and FOR811B increased urinary flow and decreased osmolar clearence and TFG. They also caused a decrease in the total and proximal transport of sodium, potassium and chloride. Only FOR011B increased levels of urinary GMPc of perfused kidneys. In LLC-MK2 cells line, only FOR 811 A demonstrated potential protective effect of respiratory dysfunction caused by I/R injury and, also caused increased nitrite / nitrate (NOx) concentration in renal tissue. In short, future experiments are needed to investigate the mechanism by which the FOR811B has the capacity of donate nitric oxide in a controlled manner and at subtoxic levels.