Genistein attenuates renal fibrosis in streptozotocin‑induced diabetic rats

Abstract

The present study aimed to investigate the antifibrogenic effects of genistein (GEN) on the kidney in streptozotocin (STZ)-induced diabetic rats and to determine the associated mechanisms. Rats were randomized into four groups: Normal control (N), STZ (S), L (STZ + low-dose GEN) and H (STZ + high-dose GEN). After 8 weeks, the fasting blood glucose (FBG) level, the ratio of kidney weight to body weight (renal index), 24-h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), renal total antioxidant capacity (T-AOC), superoxide dismutase (SOD), lipid peroxidation (LPO), malondialdehyde (MDA) and hydroxyproline (Hyp) contents were measured. The histomorphology and ultrastructure of the kidney were also assessed. In addition, mRNA expression levels of transforming growth factor-β1 (TGF-β1) and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), TGF-β1, mothers against decapentaplegic homolog 3 (Smad3), phosphorylated (p)-Smad3 and collagen IV were estimated. Compared with group N, the levels of FBG, renal index, 24-h urine protein, BUN, SCr, LPO, MDA and Hyp were increased, whereas the levels of T-AOC and SOD were decreased in group S. The structure of renal tissue was damaged, and the expression of Nrf2, HO-1 and NQO1 were reduced, whereas the expression of TGF-β1, Smad3, p-Smad3 and collagen IV were increased in group S. Compared with group S, the aforementioned indices were improved in groups L and H. In conclusion, GEN exhibited reno-protective effects in diabetic rats and its mechanisms may be associated with the inhibition of oxidative stress by activating the Nrf2-HO-1/NQO1 pathway, and the alleviation of renal fibrosis by suppressing the TGF-β1/Smad3 pathway.

Rutin Restore Biochemical Changes, Oxidative Stress and Betatrophin Level in STZ-Induced Diabetic Rats

“…Our data are in agreement with previous findings that showed streptozotocin (STZ)-induced diabetic rats caused increased MDA level that reflect the levels of tissue lipid peroxidation and decreased SOD activity that scavenge superoxide products in kidney tissue [36]. Glucose is oxidized to reactive ketoaldehyde and superoxide radicals.…”

“…Past investigations announced that diabetic rats indicated essentially expanded serum uric acid (SUA), serum creatinine (SCr), and urea nitrogen (BUN) levels [35] and [36].…”

Decoy receptor 2 mediation of the senescent phenotype of tubular cells by interacting with peroxiredoxin 1 presents a novel mechanism of renal fibrosis in diabetic nephropathy

“…(i) Western blotting showed phospho-PRDX1 (p-PRDX1) expression in control and HG after transfer DcR2 siRNA or (continued) the specific PTK inhibitor genistein. 37 These results suggest that DcR2 regulates the phosphorylation of PRDX1 through the "bridge" of PTK.…”

“…As shown in Figure 8k and l, PRDX1 phosphorylation levels were markedly inhibited by genistein, a specific inhibitor of PTK. 37 These data suggest that DcR2 regulates the phosphorylation level of PRDX1 through PTK.…”

The Role of Black Soybean and Purple Sweet Potato Active Compound on Advanced Glycation End-Product in Streptozotocin-Induced Type 2 Diabetes Mellitus Rat

“…Jia et al reported that the rats were given with genistein can attenuate renal fibrosis in STZ-induced diabetic rats. Supplementation with genistein for 8 weeks also increased endogenous antioxidant superoxide dismutase and decreased lipid peroxidase and malondialdehyde (MDA) [22]. also reported that supplementation on early stage of diabetic-induced renal damage can decrease level of inflammation markers such as nuclear factor kappa B (NFκB), tumor necrosis factor α (TNF-α), dan cyclooxygenase-1 (COX-1) [23].…”