Epigenetic Modulation of Autophagy Genes Linked to Diabetic Nephropathy by Administration of Isorhamnetin in Type 2 Diabetes Mellitus Rats

Abstract

<b>Aim:</b> To assess isorhamnetin efficacy for diabetic kidney disease in a Type 2 diabetes mellitus rat model, through investigating its effect at the epigenetic, mRNA and protein levels. <b>Materials & methods:</b> Type 2 diabetes mellitus was induced in rats by streptozotocin and high-fat diet. Rats were treated with isorhamnetin (50 mg/kg/d) for 4 or 8 weeks. Fasting blood glucose, renal and lipid profiles were evaluated. Renal tissues were examined by light and electron microscopy. Autophagy genes (<i>FYCO1, ULK, TECPR1</i> and<i> WIPI2</i>) and miR-15b, miR-34a and miR-633 were assessed by qRT-PCR, and LC3A/B by immunoblotting. <b>Results:</b> Isorhamnetin improved fasting blood glucose, renal and lipid profiles with increased autophagosomes in renal tissues. It suppressed miRNA regulation of autophagy genes. <b>Conclusion:</b> We propose a molecular mechanism for the isorhamnetin renoprotective effect by modulation of autophagy epigenetic regulators.