AUTHOR=Gomes Isabele B., Porto Marcella L., Santos Maria Carmen L., Campagnaro Bianca P., Gava Agata L., Meyrelles Silvana S., Pereira Thiago M., Vasquez Elisardo C. TITLE=The protective effects of oral low-dose quercetin on diabetic nephropathy in hypercholesterolemic mice JOURNAL=Frontiers in Physiology VOLUME=Volume 6 - 2015 YEAR=2015 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2015.00247 DOI=10.3389/fphys.2015.00247 ISSN=1664-042X ABSTRACT=Aims: Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease, and the incidence of DN is increasing worldwide. Considering our previous report indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg) demonstrated renoprotective, anti-oxidative and anti-apoptotic effects in the C57BL/6J model of diabetic nephropathy, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE-/-). Methods: DN was induced by streptozotocin (100 mg/kg/day, for 3 days) in adult apoE-/-mice. Six weeks later, the mice were divided into the following groups: diabetic apoE-/- mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks), diabetic ApoE-/- mice treated with vehicle (DV) and non-treated non-diabetic (ND) mice. Results: Quercetin treatment caused a reduction in polyuria (~30%), glycemia (~25%), abolished the hypertriglyceridemia and had significant effects on renal function, including decreased proteinuria (~15%) and creatininemia (~30%), which were accompanied by beneficial effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight. Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical and morphological modifications. Thus, this translational study highlights the importance of quercetin as a potential nutraceutical for the management of DN, including in diabetes associated with dyslipidemia.