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

• Published in: Biomedicine & pharmacotherapy Vol. 129; p. 110483
• Main Authors: Mabuza, Lindokuhle Patience, Gamede, Mlindeli Wilkinson, Maikoo, Sanam, Booysen, Irvin Noel, Ngubane, Phikelelani Siphosethu, Khathi, Andile
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.09.2020; Elsevier
• Subjects: Albuminuria - etiology; Albuminuria - prevention & control; Aldosterone - metabolism; Animals; Antioxidants; Biomarkers - blood; Biomarkers - urine; Cell Adhesion Molecules - metabolism; Creatinine - metabolism; Diabetic Nephropathies - etiology; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - physiopathology; Diabetic Nephropathies - prevention & control; Diabetic nephropathy; Diet, High-Fat; Dietary Carbohydrates; Dietary intervention; 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; Podocin ruthenium(II) Schiff base complex; Pre-diabetes; Prediabetic State - drug therapy; Prediabetic State - etiology; Prediabetic State - metabolism; Rats, Sprague-Dawley; Risk Factors; Ruthenium - pharmacology; Uracil - analogs & derivatives; Uracil - pharmacology; Urea - metabolism; Antioxidants; Podocin ruthenium(II) Schiff base complex; Diabetic nephropathy; Dietary intervention; Pre-diabetes
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.110483

•Ruthenium(II) complex reduced blood glucose, fluid intake and urinary output.•Restored plasma and urinary electrolytes handling.•Normalized oxidative stress and antioxidant defence enzymes.•Reduced mRNA expression of podocin in urine, aldosterone and KIM-1 concentrations.•Improved renal function and prevented the progression of DN. 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.