Amelioration of diabetic nephropathy by oral administration of d-α-tocopherol and its mechanisms

Abstract

Diabetic nephropathy (DN) is a diabetic vascular complication, and abnormal protein kinase C (PKC) activation from increased diacylglycerol (DG) production in diabetic hyperglycemia is one of the causes of DN. Diacylglycerol kinase (DGK) converts DG into phosphatidic acid. In other words, DGK can attenuate PKC activity by reducing the amount of DG. Recently, we reported that intraperitoneally administered d-α-tocopherol (vitamin E, αToc) induces an amelioration of DN in vivo through the activation of DGKα and the prevention of podocyte loss. However, the effect of the oral administration of αToc on DN in mice remains unknown. Here, we evaluated the effect of oral administration of αToc on DN and its molecular mechanism using streptozocin-induced diabetic mice. Consequently, the oral administration of αToc significantly ameliorated the symptoms of DN by preventing the loss of podocytes, and it was revealed that the inhibition of PKCactivity was involved in this amelioration.

The mechanisms of ameliorating effect of a green tea polyphenol on diabetic nephropathy based on diacylglycerol kinase α

“…Additionally, we reported that oral administration of αToc ameliorated DN in mice. In other words, we found the possibility that the compound that activates DGKα can ameliorate DN 25 . However, the oral consumption of αToc did not ameliorate DN in a human trial 26 .…”

“…At the end of the experiments, all the mice were anesthetized, and then, kidney was collected. Urine albumin excretion measurement was performed by following the method we published previously 25 .…”

“…Immunofluorescent staining of kidney was performed by following the method we published previously using the nephrin antibody (GP-N2, PROGEN Biotechnik, Germany) as the primary antibody 25 .…”

Effect of Peroxisome Proliferator-Activated Receptor-Alpha-Agonists on Diabetes-Induced Acute Kidney Injury: Role of Oxidative Stress and Hyperlipidemia

“…There are several reasons for kidney damages, the At present, angiotensin-converting enzyme (ACE) inhibitors such as captopril, lisinopril, and fosinopril are employed to treat diabetic nephropathy [11]. However, clinical evidence suggests that ACE inhibitors are not sufficient to control the symptoms of nephropathy [3,12,13]. The present study has been aimed to explore the potential use of PPAR-α to prevent diabetic-induced AKI.…”

“…The strong association between diabetes and vascular endothelial dysfunction and mediated nephropathy is demonstrated in various studies. Frequently, the strong correlations between oxidative stress and hyperlipidemia in the induction of nephropathy have been reported [5,13]. In diabetes, the reactive oxygen species (ROS) one of the main culprits plays a key role in the progression of pathophysiological processes of renal diseases.…”