GW501516 Ameliorates A Fructose-Induced Inflammation Independent of AT1r Downregulation in Kidney

Abstract

AT1r high activation is linked to low-grade inflammation and oxidative stress, which yield impaired renal function. This study aimed to verify if GW501516 could improve damage in the kidney of mice with high activation of AT1r. Mice were fed a high-fructose diet (HFru) for eight weeks to induce an activation of the AT1r, whereas the control group received standard chow. The animals were randomly divided into four groups and the administration of GW501516 lasted three weeks. Morphological outcomes, urine and plasma determinations were assessed. Renin and ACE/AT1r axis protein and gene expression were evaluated as well as inflammatory cytokines and proteins. Also, the protein and gene expression of the antioxidant enzymes were verified. GW501516 improved systolic blood pressure and urinary parameters in HFru group. Although GW501516 had no effects either on ACE/AT1r axis or renin expression, it improved the inflammatory state, with increased IκB-α protein expression and decreased ERK and JNK phosphorylation. No differences were found in oxidative stress. We conclude that GW501516 acts downstream AT1r activation, improving inflammatory pathways in the kidney of HFru fed model. This is the first report demonstrating the anti-inflammatory actions of GW501516 upon kidney independently of AT1r downregulation in an HFru model.