Análise do efeito do Sildenafil sobre células-tronco hematopoiéticas em camundongos ateroscleróticos

Abstract

A decline in the functionality of stem cells may be a key component in the pathogenesis of cardiovascular diseases. In atherosclerosis, there is an increase in endogenous genotoxic agents, such as reactive oxygen species (ROS), which can cause oxidative damage in DNA. Considering previous report that sildenafil, an inhibitor of phosphodiesterase 5 (PDE5), have antioxidant effects, in the present study we evaluated the effect of this drug on ROS levels, on pro-oxidant and antioxidant systems, on genotoxicity, on DNA repair kinetics and on apoptosis in hematopoietic stem cells (HSC) of atherosclerotic apoE knockout mice (apoE-/-). For this study were used male 20-week old apoE-/- mice. Animals were distributed into three different groups: apoE−/− mice administered with the PDE5 inhibitor sildenafil (apoE−/− sildenafil, Viagra® , 40 mg/kg/day, for 3 weeks, by oral gavage, n=25), apoE-/- mice administered with vehicle (apoE-/- vehicle, n=25) and Wild-type C57Black/6 mice (C57 vehicle, n=25). Then, animals were euthanized, blood collected for analysis of the lipid profile. The HSC were isolated by cell culture for assessed of ROS production, DNA damage, DNA repair kinetics and apoptosis by flow cytometry. Statistical comparisons were done by ANOVA, followed by Bonferroni’s post hoc test.