A flavonoid fraction purified from Rutaceae aurantiae (DaflonR) inhibiting AGE formation, reduces urinary albumin clearance and corrects hypoalbuminemia in normotensive and hypertensive diabetic rats

Aim: Advanced glycation endproducts (AGEs) have been shown to contribute to alteration of glomerular permselectivity to proteins in diabetes. Oxidative stress is required for AGE formation. Therefore we studied the effect of an antioxidant micronized purified flavonoid fraction (MPFF, Daflon(R) 500 mg), on urinary albumin clearance in diabetic rats. Methods: Hyperglycaemia was induced by streptozotocin 55 mg/kg IM at days 0 and 7 in normotensive Wistar rats (NWR, diabetes duration 5 months) or hypertensive Wistar Kyoto rats (SHR, diabetes duration 2 months). MPFF was administered at 300 mg/kg/day, from day -2 until sacrifice. Results: After 5 months of diabetes in NWR, MPFF reduced albumin clearance from 729 +/- 92 to 392 +/- 60 nl/min/kg, p < 0.01, and restored albuminemia from 20.4 +/- 0.9 to 24.0 +/- 1 g/l, p < 0.05; albumin fractional clearance was significantly diminished in the flavonoid-treated diabetic rats (0.360 +/- 0.037 parts per thousand versus 1.335 +/- 0.430 parts per thousand in the diabetic controls, p < 0.001); MPFF did not significantly modify blood glucose and plasma fructosamine levels. After 2 months of diabetes in SHR, MPFF reduced albumin clearance from 243 +/- 121 to 101 +/- 47 nl/min/kg, p < 0.05, and restored albuminemia from 21.1 +/- 1.6 to 26.7 +/- 2.2 g/l (p < 0.05); MPFF also decreased plasma fluorescence characteristic of AGEs (p < 0.02). Besides hesperetin, a main metabolite of MPFF recovered in plasma, inhibited in vitro the formation of the crosslinking AGE pentosidine in collagen incubated with high glucose (p < 0.001). Conclusion: Our results confirm the role of glycoxidative stress in diabetic nephropathy. MPFF might be useful as complementary treatment for preventing diabetic microangiopathy. (C) 2014 Elsevier Ireland Ltd. All rights reserved.