Ellagic acid protects rats from chronic renal failure via MiR-182/FOXO3a axis

Abstract

Studies showed that ellagic acid (EA) can significantly improve kidney function, but the renal-protective effects of EA and the potential mechanism require adequate elucidation. This study investigated the mechanisms of EA in chronic renal failure (CRF) injury. A rat model of CRF was established by 5/6 nephrectomy. The body weight, urine volume and urine protein content of the rat model of CRF with EA treatment (0/20/40 mg/kg/day) were recorded. Hematoxylin&eosin (H&E) staining, Masson staining and TUNEL were used for histopathological observation. Serum levels of creatinine value, blood urea nitrogen, superoxide dismutase, glutathione, malondialdehyde, tumor necrosis factor-α, interleukin-6 and intercellular cell adhesion molecule-1 were determined using enzyme-linked immunosorbent assay (ELISA) kits. The expressions of genes involved in CRF damage were detected by quantitative real-time PCR (qRT-PCR) and western blot. The relationships among EA, miR-182 and FOXO3a were verified by TargetScan 7.2, dual-luciferase assay and rescue experiments. In this study, EA treatment significantly increased the body weight, but reduced urination and urine protein content, renal tissue damage, collagen deposition, inflammation and the contents of serum creatinine (Scr), blood urea nitrogen (BUN), and malondialdehyde (MDA), and improved the antioxidant capacity of CRF rats. Moreover, EA treatment inhibited miR-182, TGF-β1, fibronectin and Bax levels, and promoted those of FOXO3a and Bcl-2 in CRF rats. Additionally, miR-182 specifically targeted FOXO3a, and effectively reduced the renal-protective effect of EA. Further research found that overexpressed FOXO3a partially reversed the inhibitory effect of miR-182 on CRF rats. Our results suggest that EA might reduce CRF injury in rats via miR-182/FOXO3a.