Our previous studies have shown that supplementation with 17-β estradiol (E2) from the onset of diabetes attenuates diabetic nephropathy. But, E2 is accompanied by feminizing effects as well as adverse side effects on other organs. The current study examined the renoprotective effects of a selective estrogen receptor modulator, raloxifene (RAL), in an experimental model of diabetic nephropathy. RAL activates estrogen receptors and estrogen receptor-mediated cellular events without the side effects of E2.
The study was performed in Sprague-Dawley non-diabetic (ND), streptozotocin (STZ)-induced diabetic (D) and STZ-induced diabetic+raloxifene (D+RAL) rats (n=6/group).
After 12 weeks of treatment, D was associated with increased albumin excretion (UAE; ND, 4.2±0.4; ND, 41.3±9.0 mg/day), glomerulosclerosis (GSI; ND, 0.26±0.04; D, 1.86±0.80 AU), tubulointerstitial fibrosis (TIFI; ND, 0.37±0.05; D, 2.12±0.50 AU), increased collagen type I (CI; ND, 1.31±0.07; D, 4.65±0.09 ROD), collagen type IV (CIV; ND, 0.64±0.03; D, 1.37±0.11 ROD) and transforming growth factor beta protein expression (TGF-β; ND, 0.65±0.08; D, 1.25±0.10 ROD), increased density of CD68-positive cells (CD68; ND, 1.37±3.02; D, 29.2±1.74 cells/mm2) and increased plasma levels of interleukin-6 (IL-6; ND, 14.8±5.0; D, 51.3±14.0 pg/ml). Treatment with RAL partially or fully attenuated these processes (UAE, 21.0±5.0 mg/day; GSI, 0.40±0.06 AU; TIFI, 0.20±0.04 AU; CI, 2.55±0.49 ROD; CIV, 0.70±0.09 ROD; TGF-β, 0.91±0.08 ROD; CD68, 6.03±2.38 cells/mm2; IL-6, 31.2±5.0 pg/ml).
Our data indicate that treatment with RAL attenuates albuminuria and renal structural changes associated with diabetes.