Abstract
Diabetic nephropathy (DN) is a consequence of diabetes mellitus (DM). DM is associated temporal changes in renal angiotensin II (ANG II) release and multiple mediators leading to DN. These changes were evaluated using early ANG II blocker valsartan as a DN renoprotective drug. Adult male Wister rats were divided into (i) vehicle group; (ii) valsartan received oral 30 mg/Kg/day; (iii) diabetic received single 50 mg/Kg intraperitoneal streptozotocin injection; (iv) renoprotection, valsartan treated-diabetic rats after 7 days from DM. Other group of diabetic animals assigned to receive late valsartan intervention from week 9 to 12 of DM. The renoprotective effect evaluated at 4th, 8th, 12th weeks. DN effects on urine albumin excretion, blood pressure and renal ANG II were measured. Urinary nephrin and kidney injury molecule-1 biomarkers, renal ANGPTL2, and toll-like receptor 4 (TLR 4) mRNA expression were tested. DN-initiated fibrotic markers integrin, α-smooth muscle expression and collagen IV and apoptotic protein caspase 3 were tested. DM induced changes starting from the 4th week. At 12th week, early valsartan intervention showed a significant reduction in ANG II, ANGPTL2 and TLR 4 expression and improvement in albuminuria, blood pressure, urinary biomarkers, fibrotic and apoptotic markers, more than the late intervention. Early inhibition of ANG II in diabetes is associated with decrease in ANGPTL2 and TLR 4 proteins and fibrotic changes. This observation helps in understanding DN pathophysiology and its therapeutic approaches.
The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation
