Protective Effects of Kaempferitrin on Advanced Glycation End Products Induce Mesangial Cell Apoptosis and Oxidative Stress.

Wenxian Jiang,Tianliang Zhang,Min Zuo,Di Liu,Wanzhong Li,Chunzhen Zhao,Rongshen Wang

doi:10.3390/ijms19113334

Wenxian Jiang, Tianliang Zhang + Show 5 more

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https://doi.org/10.3390/ijms19113334

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Abstract

Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) both play important roles in diabetic nephropathy (DN). Previous studies have identified glomerular mesangial cells (GMCs) injury as a key early risk factor in the development of DN. Kaempferitrin (KM) is a potent antioxidant with hypoglycemic action. Although KM is known to protect against AGE-induced damage in GMCs, the effects and the mechanisms by which they occur are poorly understood. In this study, cultured rat GMCs were exposed to AGE-induced oxidative stress (OS) to model DN in vitro. Reactive oxygen species (ROS) was analyzed by 2′,7′-dichlorofluorescin diacetate (DCFH-DA). Superoxide dismutase (SOD) and malondialdehyde (MDA) were studied using commercial kits. Mitochondrial membrane potential (Δψm) was measured by rhodamine 123. Hoechst 33258 and annexin V and propidium iodide (PI) double staining were performed to observe the apoptosis states in GMCs, whereas apoptosis and protective mechanism in AGE-induced GMCs were investigated by Western blot. The data revealed that KM effectively increased SOD activity, decreased MDA levels, suppressed ROS generation, and protected against OS in AGE-induced GMCs. Treatment with KM also inhibited the expression of collagen IV and transforming growth factor-β1 (TGF-β1), improved mitochondrial membrane potential recovery, and suppressed the mitochondrial/cytochrome c-mediated apoptosis pathway through the expression of anti-apoptotic factors in GMCs in vitro. These findings suggest that KM may be a new potential agent in the treatment of DN in future.

Highlights

Diabetes mellitus (DM) is a chronic metabolic disorder associated with long-term damage and failure of various organs [1]
To determine the effect that KM has on the viability of advanced glycation end products (AGEs)-treated glomerular mesangial cells (GMCs), cells were treated with different concentrations of KM (10, 20, 35, 70, 104, 140, 175, and 210 μM) or AGEs (160 μg/mL) for 24 h
The cell viability of GMCs treated with AGEs alone decreased as compared to that of the control group, (Figure 1; p < 0.01)

Summary

Introduction

Diabetes mellitus (DM) is a chronic metabolic disorder associated with long-term damage and failure of various organs [1]. Diabetic nephropathy (DN) is a serious and common chronic microvascular complication of DM [2], that is the main cause of mortality in patients with diabetes, as well as a major contributor to the high prevalence of end-stage renal disease (ESRD) worldwide [3]. The global prevalence of DM is growing rapidly, especially in developing countries, and the incidence rates of both DN and ESRD continue to increase [4]. Hyperglycemia is accompanied by an accelerated rate of formation of advanced glycation end products (AGEs). AGEs, which are derived from reducing the non-enzymatical reaction of sugars with amino groups of protein, play an important role in the pathogenesis of diabetic complications [5]. The underlying molecular mechanisms behind DM-induced renal damage are still poorly understood

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