Sporidiobolus pararoseus wall-broken powder ameliorates oxidative stress in diabetic nephropathy in type-2 diabetic mice by activating the Nrf2/ARE pathway

Abstract

In type 2 diabetes mellitus (T2DM), hyperglycemia promotes oxidative stress and eventually leads to diabetic nephropathy (DN). Sporidiobolus pararoseus is reported to exhibit enhanced anti-oxidation properties. However, its role in DN remains obscure. This study aimed to determine the antioxidative effects of a Sporidiobolus pararoseus wall-broken powder (SPP) supplement on DN and investigate the possible underlying mechanisms. A model of T2DM was successfully established, and C57BL/6J male mice were fed a high-fat diet for 4 weeks and then injected with streptozotocin (100 mg per kg per day) for three consecutive days. After eight weeks of intervention, SPP strongly lowered fasting glucose levels, serum creatinine, serum urea nitrogen, urinary albumin and reduced glomerular hypertrophy and mesangial matrix expansion. In addition, SPP increased the activities of SOD, T-AOC, CAT, and GST and decreased the amount of MDA. Furthermore, it was revealed that SPP significantly abrogated oxidative stress not only by activating the Nrf2 gene but also by activating two Nrf2-targeted antioxidative genes (NQO-1 and HO-1) compared with metformin hydrochloride, which is widely accepted as a diabetes drug. Our study showed that SPP has antioxidant properties and delays the progression of DN; the underlying mechanism may be associated with activation of the Nrf2/ARE pathway.

Fig. 1. Effects of S. pararoseus JD-2 wall-broken powder on body weight (A), daily water intake (B), daily food intake (C) and fasting blood glucose (D) in diabetic nephropathy mice.

Fig. 2. Effects of S. pararoseus JD-2 wall-broken powder on urine volume for 24 h after 8 weeks of treatment (A), urinary albumin after 8 weeks of treatment (B), serum creatinine (C), and serum urea nitrogen (D) in diabetic nephropathy mice. Values are expressed as the mean ± SEM of 8 mice per group. Model group vs. control group: ^###p < 0.001. MH group, SPP group vs. Model group: *p < 0.05, **p < 0.01, ***p < 0.001.

Fig. 3. Effects of S. pararoseus JD-2 wall-broken powder on serum SOD (A), serum MDA (B), serum T-AOC (C), kidney SOD (D), kidney MDA (E) and kidney T-AOC (F) in diabetic nephropathy mice. Effects of S. pararoseus JD-2 wall-broken powder on kidney histoarchitecture of high-fat diet and STZ-induced early diabetic nephropathy in mice. Kidney sections were stained with periodic acid-Schiff staining (H&E, PAS) (G) (original magnification, ×400) and hematoxylin and eosin (original magnification, ×400). Values are expressed as the mean ± SEM of 8 mice per group. Model group vs. control group: ^##p < 0.01, ^###p < 0.001. MH group, SPP group vs. Model group: *p < 0.05, **p < 0.01, ***p < 0.001.

Fig. 4. Effects of S. pararoseus JD-2 wall-broken powder on the mRNA expression of proteins in the kidney. The mRNA levels of Nrf2, NQO1, CAT, GST and HO-1 were determined by qPCR (A). Effects of S. pararoseus JD-2 wall-broken powder on kidney immunohistochemical staining of high-fat diet and STZ-induced early diabetic nephropathy in mice. Immunohistochemical staining for Nrf2 and NQO1 with brown color (original magnification, ×400) (B). Values are expressed as the mean ± SEM of 8 mice per group. Model group vs. control group: ^##p < 0.01, ^###p < 0.001. MH group, SPP group vs. Model group: *p < 0.05, **p < 0.01, ***p < 0.001.