High Dose Vitamin E Attenuates Diabetic Nephropathy via Alleviation of Autophagic Stress

Abstract

It has been reported that autophagic stress, which is involved in many diseases, plays a key role in the development of diabetic nephropathy (DN). In this study, we investigated the effects of high dose vitamin E on renal tubular epithelial cells and autophagic stress-related mechanisms in diabetes condition. In diabetic rats, high dose vitamin E treatment significantly decreased the serum creatinine, urea nitrogen, urinary albumin and urinary protein, reduced the levels of LCN2, HAVCR1, LDH and 8-OHdG in urine, and attenuated the cellular apoptosis and interstitial fibrosis in renal cortex. In vitro, vitamin E could reduce the release of LCN2 and HAVCR1 and the protein levels of caspase 3 and TGF-β1, as well as improve the growth inhibition in cultured HK-2 cells after exposure to advanced glycation end products (AGEs). Also, LC3-II and SQSTM1-positive dots were significantly increased in the renal tubular epithelial cells of DN patients and diabetic rats, and in HK-2 cells after exposure to AGEs, which were markedly declined by vitamin E. In addition, we found that the autophagosome formation was not affected by AGEs, as assessed by the mRNA levels of LC3B, Beclin-1, and ATG7. However, AGEs blocked the lysosomal degradation of autophagosome, which was characterized by a decrease in the enzymatic activity of cathepsin B/cathepsin L and DQ-ovalbumin degradation in HK-2 cells, indicating that AGEs-induced accumulation of autophagic vacuoles was a sign of autophagic stress. Interestingly, vitamin E exerted a protective effect on lysosomes to reduce the autophagic stress. Taken together, we conclude that autophagic stress may play an important part in the progression of DN, and alleviation of autophagic stress though improvement of lysosomal function provides a promising novel approach for treating DN.

Evaluation of Antioxidants Supplementation on Renal, Hepatic and Cardiac Function Markers in Alloxan Induced Diabetes Mellitus Wister Rats

“…From our results, the significantly lower values of Na + and K + and HCO 3 ( Table 1) seen in the diabetic rats without supplementation (group D) compared to the diabetic rats with antioxidants supplementation of selenium and vitamin E (Group A, B and C) as well as the non-diabetic control group (group E) is in agreement with the findings of [5,9]. They all reported in their respective studies concerning the alleviation of diabetic nephropathy in rats supplemented with a dose of vitamin E. However, rats not supplemented with vitamin E had severely deranged nephritic biochemical parameters as seen in the Na + and K + and HCO 3 .…”

“…Studies have also shown that hyperglycemic induced oxidative stress has been one of the major link between diabetes and diabetic complications; ranging from endothelial dysfunctions, alterations and distortions of pancreatic beta cells; insulin resistance and as well as microvascular and macrovascular complications [4]. In diabetic patients the most commonly known oxidative processes are glycoxidation and peroxidation which results to the formation of advanced glycated end-products (AGE) and Lipid peroxylradicals respectively [3,4,5]. More so, free radicals can lead to pathological conditions likedyslipidaemia, nephropathy, retinopathy, neuropathy, hepatopathy, and cardiomyopathy, which are major microvascular complications.…”

Accelerated Kidney Aging in Diabetes Mellitus

“…Antioxidants (including vitamin C, vitamin E, and zinc) may protect against early renal damage [204]. High-dose vitamin E supplements in the treatment of DN resulted in a notable decrease in urine protein, which may be partly associated with the alleviation of autophagic stress in TECs [117,205]. Nicotinamide adenine dinucleotide (NAD) functions as a coenzyme in redox reactions and mediates many biological processes, including metabolism and aging, as well as metabolic diseases like DM [206,207].…”

Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation

“…Vitamin E can inhibit AGE formation in vitro [98], probably due to the protective role that vitamin E exerts on lysosomes to reduce autophagic stress [101]; however, this has only been studied in DN to our knowledge and has yet to show the same properties in retinal tissues.…”