Diabetic nephropathy induced by methylglyoxal: gallic acid regulates kidney microRNAs and glyoxalase1–Nrf2 in male mice

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.

Keywords:

• Methylglyoxal
• diabetic nephropathy
• Nrf2
• gallic acid
• glyoxalase1

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available on request from the corresponding author.

Additional information

Funding

This paper is a part of the Ph.D. thesis of Shahnaz Mojadami that labelled the Physiology Research Centre project (APRC-9616) and was financially supported by the vice-chancellor of research affairs of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.