Novel biphenyl compound, VMNS2e, ameliorates streptozotocin-induced diabetic nephropathy in rats

• Published in: Journal of diabetes 2010-12, Vol.2 (4), p.282-289
• Main Authors: KURUNDKAR, Sucheta B., SACHAN, Narsingh, KODAM, Kisan M., KULKARNI, Vithal M., BODHANKAR, Subhash L., D'SOUZA, Serena, VANAGE, Geeta, GHOLE, Vikram S.
• Format: Article
• Language: English
• Subjects: Albuminuria - drug therapy; Animals; biphenyl compound; Biphenyl Compounds - chemistry; Biphenyl Compounds - therapeutic use; Blood Glucose - drug effects; Blood Urea Nitrogen; Body Weight; Catalytic Domain - drug effects; Creatinine - blood; Creatinine - urine; diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetic Nephropathies - drug therapy; diabetic nephropathy; Glomerular Basement Membrane; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - therapeutic use; Insulin - blood; Kidney - drug effects; Kidney - ultrastructure; Male; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Proteinuria - drug therapy; Rats; Rats, Sprague-Dawley; streptozotocin; VMNS2e
• ISSN: 1753-0393; 1753-0407
• DOI: 10.1111/j.1753-0407.2010.00094.x

Aim:  To study the effect of a new biphenyl synthetic compound showing interactions with the active site of protein tyrosine phosphatase 1B by docking and molecular dynamics, VMNS2e in streptozotocin‐induced diabetic nephropathy in rats with various renal function parameters and renal ultrastructure. Methods:  Streptozotocin (55 mg/kg)‐induced diabetic rats were orally treated once daily with VMNS2e (30, 60, and 120 mg/kg) for 8 weeks. The body weight and blood glucose levels of the rats were recorded during the study period. After 8 weeks of treatment creatinine clearance, urinary protein, blood urea nitrogen, urinary albumin excretion rate, and insulin levels were measured. An ultrastructure study of the kidney tissue was performed and the glomerular basement membrane thickness was measured. Results:  Eight weeks of VMNS2e treatment significantly reduced the fasting blood glucose level, attenuated elevating blood urea nitrogen levels, and reduced glomerular basement membrane thickness. Conclusion:  It is concluded that VMNS2e treatment at 30 and 60 mg/kg, when given for 8 weeks, partly ameliorated early diabetic nephropathy in diabetic rats.