Effect of Combined Vitamin E and Insulin Administration on Renal Damage in Diabetic Rats Fed a High Cholesterol Diet

Abstract

Diabetic nephropathy is characterized by persistent proteinuria, hypertension and declining renal function. Microalbuminuria is detected at the early stage of diabetic nephropathy. Approximately 30-40% of type 1 diabetic patients have renal complications, which are a major cause of mortality.1-3) Diabetes mellitus is a disease characterized by hyperglycemia. On the other hand, hyperlipidemia in addition to hyperglycemia has been frequently observed in insulin-dependent 4,5) and non-insulin-dependent diabetic patients. 6)Likewise, hyperlipidemia was also observed in experimental insulin-dependent 7,8) and non-insulin-dependent diabetic animal models.9) Hyperlipidemia in addition to hyperglycemia has been thought to be a major risk factor for the development and progression of diabetic complications such as nephropathy. 10,11) Recently, oxidative stress has been indicated to play an important role in the development and progression of diabetic nephropathy.12) Under hyperglycemic conditions, oxygen-derived free radicals are produced mainly through a glycation reaction. 13,14) Scheuer et al. 15) have shown that hyperlipidemia can aggravate glomerulosclerosis and chronic tubulointerstitial damage in kidneys and oxidative stress contributes to the deleterious effects of hyperlipidemia on renal damage. Chen et al. 16) have demonstrated that oxidized low density lipoprotein (LDL) enhances superoxide production by diabetic rat glomeruli. Their findings strongly suggest that oxidized LDL may play important roles in the pathogenesis of diabetic nephropathy through increased generation of oxygen-derived free radicals.It is well known that vitamin E, a lipid-soluble and antioxidant vitamin, protects unsaturated fatty acid, a main component of cell membranes, from attack by oxygen-derived free radicals. There have been a few reports concerning the effect of vitamin E on experimental diabetes. Je et al. 17) reported that vitamin E inhibited the oxidation of proteins in organs such as liver and kidney in streptozotocin (STZ)-induced diabetic rats. Baydas et al. 18) have shown that vitamin E as well as melatonin protects organisms from oxidative damages. On the other hand, insulin has been widely used for the treatment of type 1 (insulin-dependent) diabetes mellitus as hormone supplement therapy. These findings suggest that insulin in combination with vitamin E may exert a more beneficial effect than insulin alone on diabetic nephropathy. Recently, we reported that a long-term high cholesterol diet for STZ-induced diabetic rats not only precipitated the onset of cataracts but also increased the incidence of this complication with an increased death rate.19) Furthermore, in this report, we demonstrated that long-term combined treatment with vitamin E and insulin synergistically prevents the development and progression of cataracts of STZ-induced diabetic rats fed a high cholesterol diet.In a pilot experiment, we observed that a long-term high cholesterol diet aggravated STZ-induced renal damage in rats with increased urinary ...

Vitamin E supplementation in rats with experimental diabetes mellitus: analysis of myosin-V and nNOS immunoreactive myenteric neurons from terminal ileum

“…Free radical production and decreased endogenous antioxidant defenses during DM are also directly related to micro-and macrovascular alterations (e.g., atherosclerosis) considered to be the main causes of morbidity and mortality in diabetic patients (Son 2007). The enzymes hepatic superoxide dismutase, catalase, and glutathione peroxidase are examples of endogenous antioxidants that are decreased in experimental models of streptozotocin-induced DM (Yoshida et al 2005). Several mechanisms appear to be involved in the genesis of oxidative stress in diabetes in animals and humans (type 1 and type 2 diabetic patients), including glucose autoxidation, protein glycation, advanced glycation endproduct formation, and the poliol pathway (Bonnefont-Rousselot et al 2000).…”

“…Vitamin E interferes with the process of lipid peroxidation, protecting polyunsaturated fatty acids against attack by free radicals (Yoshida et al 2005). The presence of vitamin E in neuronal cells membranes, especially the inner mitochondrial membrane, suggests its possible use in the treatment of DM.…”

Evaluation of Omega-3 on lipid Profile and Biochemical Parameters on Wister Rats

“…Further, it has been reported that diabetic rats treated with insulin show normalized lipid levels (Yoshida, M., et al, 2005).…”

“…Several studies demonstrated that water soluble portion of alcoholic extract of leaves of Azadirachtaindicapossesses significant antiinflammatory, antiserotonin,antifertility and hepatoprotective activity (Ravi, K., et al, 2004;Sekar, D.S., et al, 2005;Sharma, S.B., et al, 2003;Yehuda, et al, 2005;Sukla, R., et al, 1973;Xin, et al, 2012;Yoshida, M., et al, 2005;Zimmer, Carl., 2015;Van Dam, R.M., et al, 2002).…”

Supplementation with 0.1% and 2% vitamin e in diabetic rats: analysis of myenteric neurons immunostained for myosin-V and nNOS in the jejunum

“…Moreover, vitamin E interferes with lipid peroxidation and inhibits the enzyme phospholipase A2, thus preventing membrane phospholipid hydrolysis (15,31,36,43,45) . The present study investigated the effects of vitamin E supplementation at different concentrations (0.1% and 2%) on the general population of myenteric neurons (myosin-V-immunoreactive) and on the subpopulation of nitrergic neurons (neuronal nitric oxide synthase [nNOS]-immunoreactive) in the jejunum of rats with DM.…”