DMP-1 attenuates oxidative stress and inhibits TGF-β activation in rats with diabetic kidney disease

Abstract

Introduction: DMP-1 supplement has a satisfactory effect on diabetic kidney disease in patients with whether T1DM or T2DM. Oxidative stress and TGF-β signal pathway activation are essential in the pathogenesis of DKD. We aim to investigate the effect of DMP-1 on oxidative stress and TGF-β activation in rats with DKD.Materials and methods: Male Wistar rats were enrolled and randomly allocated into five groups: Control group, STZ group (60 mg/kg, ip), DMP-1 low dose group (0.5 g/kg/day, ig), DMP-1 medium dose group (1.0 g/kg/day, ig) and DMP-1 high dose group (2.0 g/kg/day, ig). The levels of UREA, BUN, UCr, β2-MG, mALB, NOS, CAT, MDA and T-AOC were measured after 8 weeks treatment. And rats’ left kidneys were harvested to detect the expression of TGF-β, Smad2/3 and Smad7 by immunohistochemical analysis.Results: DMP-1 treatment has protective effects on kidney injury induced by STZ, which is demonstrated as following criteria: (1) a significant reduction in levels of UREA (p < 0.05), BUN (p < 0.05), UCr (p < 0.05), β2-MG (p < 0.05) and mALB (p < 0.05) in rats treated by DMP-1 compared with the ones injected with STZ only; (2) an apparent increment levels of NOS (p < 0.05), CAT (p < 0.05) and T-AOC (p < 0.05), while reduction in level of MDA (p < 0.05) in DMP-1 groups compared with STZ group; (3) a significant inhibition of TGF-β and Smad2/3 overexpression induced by STZ in kidney tissue. What’s more, DMP-1 can increase Smad7 expression.Conclusion: DMP-1 could slow pathological process and protect kidney from DKD injury by decreasing oxidative stress and inhibiting TGF-β signal pathway activation in rats.

Protective Effect and Possible Mechanisms of Astragaloside IV in Animal Models of Diabetic Nephropathy: A Preclinical Systematic Review and Meta-Analysis

“…It is among the most severe and common microvascular complications of diabetes mellitus (Saran et al, 2015;Flyvbjerg, 2017). It is characterized by proteinuria, hypertension, and progressive renal insufficiency resulting from compromise of the glomerular filtration barrier, eventually resulting in end-stage renal disease (ESRD) in 30-40% of patients (Bjornstad et al, 2014;Saran et al, 2015;Wang et al, 2016;Du et al, 2017). Management of hypertension and hyperglycemia is the most commonly used approach for treatment of DN.…”

Combination of Ginsenoside Rg1 and Astragaloside IV reduces oxidative stress and inhibits TGF-&beta;1/Smads signaling cascade on renal fibrosis in rats with diabetic nephropathy

“… 8 , 9 The transition of renal tubular epithelial cells to myofibroblasts which synthesize excessive amounts of extracellular matrix thus leading to renal fibrosis is modulated by TGF-β through TGF-β/Smads signaling pathway. 2 Furthermore, oxidative stress and TGF-β/Smads signaling together with other disease processes interactively and rapidly promote DN. Therefore, agents with anti-oxidative or TGF-β1/Smads signaling prohibitive competence are likely to possess a therapeutic effect on DN.…”