Vitamin D Supplementation Could Enhance the Effectiveness of Glibenclamide in Treating Diabetes and Preventing Diabetic Nephropathy: A Biochemical, Histological and Immunohistochemical Study

Abstract

Diabetes mellitus is an oxidative stress-related disease characterized by hyperglycemia and a variety of complications, including nephropathy. Vitamin D has variable functions extending beyond the calcium metabolism to prevent oxidative tissue damage. We aimed to investigate whether vitamin D supplements could enhance Glibenclamide's effectiveness in treating diabetes and minimize the risk of associated pathology. Wistar rats were divided into normal control (n = 10) and diabetic (n = 30), where animals received two low doses of Streptozotocin 30 mg/kg/BW intraperitoneally to develop diabetes. The diabetic rats were then randomly divided into three equal groups: untreated, treated with Glibenclamide (0.6 mg/kg), and treated with Glibenclamide and Vitamin D3 (500 IU/kg). After eight weeks, the animals were sacrificed, and blood samples and kidney tissues were collected to evaluate biochemical, anti-oxidant, and pro-inflammatory cytokine levels and histological and immunohistochemical changes. Diabetic animals had significantly increased fasting blood glucose, lipid profile, blood urea, serum creatinine, and Malondialdehyde levels, whereas serum insulin, albumin, and the anti-oxidant enzymes superoxide dismutase and catalase were significantly decreased compared to normal control (p < 0.01). Furthermore, some renal histological changes were observed together with significantly increased immunoreactivity of anti-p53, anti-TNF-α, and anti-IL-6 antibodies when compared to the normal control. All abnormal parameters improved significantly with Glibenclamide therapy (p < 0.01), but combination therapy with vitamin D produced a much better result. In conclusion, vitamin D supplementation along with anti-diabetic medication can help prevent or reduce the severity of diabetic nephropathy due to its potent antioxidant, anti-inflammatory, and anti-apoptotic properties.

Cholecalciferol Effects on Lipid Profile of Experimental Animals: A Scoping Review

“…Consistent with Atia et al (2022), the study by Lim et al (2021) reported lower plasma triglyceride and TC levels in the diabetic mice group after 12 weeks supplemented with 300 mg and 600 mg of vitamin D3. This study also showed that vitamin D3 supplementation lowers lipogenesis and inhibits lipid accumulation by improving β-oxidation.…”

“…The study also showed that vitamin D3 supplementation reduced liver TG content, while hepatic TC levels did not significantly change (Lim et al, 2021). Atia et al (2022) showed a significant decrease (p<0.001) in TC and TG levels in diabetic rats treated with eight weeks of cholecalciferol compared with untreated diabetic rats. Wahba et al (2021) showed that vitamin D3 significantly improved the markers of obesity and serum lipids such as serum TG, TC, and TC/HDL-C ratio profile compared to untreated metabolic syndrome rats (p<0.05).…”

“…All studies used the oral route to administer cholecalciferol using various vehicles (Tsuruki et al, 1986;Philouze et al, 2022;Lee et al, 2020;Lim et al, 2021;Wahba et al, 2021;Abd and Sallam, 2022;Atia et al, 2022;Elseweidy et al, 2022;Quach et al, 2018;Surdu et al, 2021). Cholecalciferol was either administered as a single treatment or with other supplements.…”

Investigating the relationship between vitamin-D deficiency and glycemia status and lipid profile in nondiabetics and prediabetics in Saudi population

“…Moreover, numerous studies have linked vitamin D deficiency to B-cell dysfunction and insulin resistance (IR) in type 2 diabetes. [4,5] Therefore, the global increase in vitamin D deficiency may be related to the increasing prevalence of type 2 diabetes.…”

Nutritional Strategies against Diabetic Nephropathy: Insights from Animal Studies and Human Trials

“…Individuals with diabetes exhibited elevated urinary albumin and serum urea [ 62 ], as VDR overexpression can mitigate defective podocyte autophagy in DN via AMPK [ 63 ]. With vitamin D treatment, both urinary albumin and serum urea levels were diminished, and the production of inflammation-related cytokines, such as IL-6 and TNF-alpha, was downregulated [ 64 ]. Control mice displayed a significant presence of VDR in the nuclei of glomerular podocytes, while VDR levels were decreased in the DN group.…”