Amelioration of risk factors associated with diabetic nephropathy in diet-induced pre-diabetic rats by an uracil-derived diimine ruthenium(II) compound

Biomed Pharmacother. 2020 Sep:129:110483. doi: 10.1016/j.biopha.2020.110483. Epub 2020 Jul 10.

Abstract

Diabetic renal injury advances through different stages of structural and functional changes in the glomerulus, therefore treatment during the pre-diabetic state could be used as therapeutic target in the management and prevention of diabetic nephropathy (DN). Once diagnosed, dietary interventions and pharmacological therapy have been recommended to manage DN and pre-diabetic related complications. However, poor patient compliance still results, therefore newer alternative drugs are required. High fat high carbohydrates (HFHC) diet was used to induce pre-diabetes for 20 weeks. After the induction, pre-diabetic rats were randomly allocated to respective treatment groups. Subcutaneous ruthenium(II) Schiff base complex injection (15 mg/kg) was administered to pre-diabetic rats in both the presence and absence of dietary intervention once a day every third day for 12 weeks. The administration of ruthenium(II) complex resulted in reduced blood glucose, aldosterone, fluid intake and urinary output which correlated with a restoration in plasma and urinary electrolytes along with plasma antioxidants concentration. Furthermore, there was a decrease in kidney injury molecule-1 (KIM-1) concentration, albumin excretion rate (AER) albumin creatinine ratio (ACR) and mRNA expression of podocin in urine in ruthenium-treated pre-diabetic rats. Ruthenium(II) Schiff base complex ameliorated renal function while preventing the progression of DN in prediabetic-treated rats.

Keywords: Antioxidants; Diabetic nephropathy; Dietary intervention; Podocin ruthenium(II) Schiff base complex; Pre-diabetes.

MeSH terms

  • Albuminuria / etiology
  • Albuminuria / prevention & control
  • Aldosterone / metabolism
  • Animals
  • Biomarkers / blood
  • Biomarkers / urine
  • Cell Adhesion Molecules / metabolism
  • Creatinine / metabolism
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / prevention & control*
  • Diet, High-Fat
  • Dietary Carbohydrates
  • Disease Models, Animal
  • Hypoglycemic Agents / pharmacology*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Organometallic Compounds / pharmacology*
  • Oxidative Stress / drug effects
  • Prediabetic State / drug therapy*
  • Prediabetic State / etiology
  • Prediabetic State / metabolism
  • Rats, Sprague-Dawley
  • Risk Factors
  • Ruthenium / pharmacology*
  • Uracil / analogs & derivatives
  • Uracil / pharmacology*
  • Urea / metabolism

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • Dietary Carbohydrates
  • Havcr1protein, rat
  • Hypoglycemic Agents
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Organometallic Compounds
  • Aldosterone
  • Uracil
  • Ruthenium
  • Urea
  • Creatinine