Diabetic nephropathy induced by methylglyoxal: gallic acid regulates kidney microRNAs and glyoxalase1–Nrf2 in male mice
Shahnaz Mojadami, Akram Ahangarpour, Seyyed Ali Mard, Layasadat Khorsandi
Abstract
BACKGROUND: Methylglyoxal (MG) has been reported to be a toxic by-product of glycolysis and intracellular stressor compound. This study investigated the effects of gallic acid (GA) against diabetic nephropathy (DN) induced by MG in male mice. METHODS: DN was induced by methylglyoxal (600 mg/kg/day, p.o.) treated for 28 consecutive days. The animals received GA (30 mg/kg/day, p.o.) and metformin (MT) (150 mg/kg/day, p.o.) for 7 consecutive days after diabetes induction. Biochemical assays, antioxidant evaluation, microRNAs associated with fibrosis, endoplasmic reticulum stress, and histopathological analysis were examined. RESULTS: MG increased malondialdehyde, albuminuria, Nrf2, miR-192 and miR-204 expression in diabetic groups and GA decreased them. Superoxide dismutase, catalase, glyoxalase1, and miR-29a expression decreased in diabetic groups and increased in treatment with GA. CONCLUSION: Our results revealed that GA has improved DN induced by MG via amelioration of biochemical indices, histopathological aspects, oxidative stress and microRNAs associated with endoplasmic reticulum stress and fibrosis.