Vitamin D improves diabetic nephropathy in rats by inhibiting renin and relieving oxidative stress

J Endocrinol Invest. 2016 Jun;39(6):657-66. doi: 10.1007/s40618-015-0414-4. Epub 2015 Dec 21.

Abstract

Background: It is well established that the activation of the renin-angiotensin system (RAS) and the oxidative stress caused by hyperglycemia are major mediators of the development and progression of diabetic nephropathy (DN). Vitamin D may be important in maintaining podocyte health, preventing epithelial-to-mesenchymal transformation, and suppressing renin gene expression and inflammation, but its mechanism requires clarification. This study evaluated the specific mechanism of vitamin D to DN improvement.

Methods: We induced a rat model of diabetes with an intraperitoneal injection of streptozotocin (60 mg/kg). The streptozotocin-induced diabetic rats were fed normal chow for about 2 months to induce the DN model. The DN rats were then treated with irbesartan and/or calcitriol, administered intragastrically about 1 month.

Results: The rats displayed the early characteristics of DN, including increased microalbuminuria, obvious hypertrophic kidney, and a markedly increased kidney weight/bodyweight ratio. Vitamin D inhibited the compensatory increase in renin expression. Malondialdehyde, which reflects oxidative stress levels, was elevated in the DN group rats and their antioxidant capacity was significantly reduced. The irbesartan and calcitriol interventions markedly improved the renal pathology and pathophysiological changes. Irbesartan combined with vitamin D (calcitriol) more effectively ameliorated DN than irbesartan alone.

Conclusions: Vitamin D combined with angiotensin II type 1 receptor blockers exerts a synergistic effect on the treatment of DN, not only by inhibiting renin but also by reducing oxidative stress and increasing the renal antioxidant capacity.

Keywords: Angiotensin II type 1 receptor blockers; Diabetic nephropathy; Oxidative stress; Rats; Vitamin D.

MeSH terms

  • Animals
  • Biomarkers
  • Bone Density Conservation Agents / pharmacology
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism
  • Immunoenzyme Techniques
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Renin / antagonists & inhibitors*
  • Renin / genetics
  • Renin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vitamin D / pharmacology*

Substances

  • Biomarkers
  • Bone Density Conservation Agents
  • Vitamin D
  • Renin