Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy

Ghada Alomari,Alaa Aljabali,Murtaza M Tambuwala,Nesreen Bataineh,Janti Qar,Bahaa Al-Trad,Mazhar Al-Zoubi,Salehhuddin Hamdan

doi:10.1007/s13346-019-00675-6

Abstract

Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.

Highlights

Diabetic nephropathy (DN) is the major cause of endstage renal failure and mortality in diabetic patients all over the world [1]
The results of the present study showed that the levels of urinary albumin were significantly increased in diabetic rats which were associated with the loss of podocytes, widening and effacement of foot process, and decrease in the staining intensity of nephrin and podocin
Our data indicated that AuNPs significantly reduced albuminuria and the podocyte ultrastructural abnormalities and restored the staining intensity of nephrin and podocin, suggesting a protective effect for AuNPs on the structure of podocytes in the diabetic conditions

Summary

Introduction

Diabetic nephropathy (DN) is the major cause of endstage renal failure and mortality in diabetic patients all over the world [1]. In DN, the first detected histological alteration usually appears on glomeruli as a thickening of the glomerular basement membrane (GBM) and tubular basement membrane (TBM) [2] Both GBM thickening and glomerular hyperfiltration lead to the progression of microalbuminuria, while the leading cause for renal insufficiency in DN is the mesangium expansion, which develops at a later stage [3]. (2020) 10:216–226 fibronectin, and laminin in the mesangium and renal tubulointerstitium of the glomerulus and basement membranes [5] This subsequently resulted from their increased production, decreased degradation, or both which eventually resulting in renal fibrosis and DN [2, 4,5,6]. Chronic hyperglycemia is the major initiator of these changes through increased oxidative stress, overproduction and action of advanced glycation end products (AGE), and activation of several growth factors, such as transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF-A) [7]

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