Crocin attenuates endoplasmic reticulum stress in methylglyoxal-induced diabetic nephropathy in male mice: MicroRNAs alterations and glyoxalase 1-Nrf2 signaling pathways.

Objectives: Accumulation of methylglyoxal (MGO) occurs in diabetes. MicroRNA-204 is an important intracellular marker in the diagnosis of endoplasmic reticulum stress. Crocin (Crn) has beneficial effects for diabetes, but the effect of Crn on MGO-induced diabetic nephropathy has not been investigated. The current research evaluated the effects of Crn and metformin (MET) on diabetic nephropathy induced by MGO in male mice. Materials and Methods: In this experimental study, 70 male NMRI mice were randomly divided into 7 groups: control, MGO (600 mg/Kg/d), MGO+Crn (15, 30, and 60 mg/kg/d), MGO+MET (150 mg/kg/d), and Crn60 (60 mg/kg/d). Methylglyoxal was gavaged for four weeks. After proving hyperglycemia, Cr and MET were administered orally in the last two weeks. Biochemical and antioxidant evaluations, microRNA expression, and histological evaluation were assessed. Results: The fasting blood glucose, urine albumin, blood urea nitrogen, plasma creatinine, malondialdehyde, Nrf2, miR-204, and miR-192 expression increased in the MGO group. These variables decreased in Crn-treated animals. The decreased levels of superoxide dismutase, catalase, glyoxalase 1, Glutathione, and miR-29a expression in the MGO group improved in the diabetic-treated mice. Histological alterations such as red blood cell accumulation, inflammation, glomerulus diameter changes, and proximal cell damage were also observed. Conclusion: Our study indicated that Crn and MET attenuated renal damage by inhibiting endoplasmic reticulum stress.