WJ-39, an Aldose Reductase Inhibitor, Ameliorates Renal Lesions in Diabetic Nephropathy by Activating Nrf2 Signaling

Figure 2

WJ-39 inhibited the activity of aldose reductase (AR) and ameliorated renal dysfunction and fibrosis in streptozotocin- (STZ-) induced diabetic nephropathy (DN) rats. (a) AR activity in renal cortex tissues was detected by using a biochemical chromatometry kit. (b) AR protein levels in renal cortex tissues were detected by western blotting and quantified. (c) Blood glucose levels and (d) area under the curve (AUC) of SD rats () and STZ-induced diabetic rats () in the oral glucose tolerance test (OGTT) were detected one week after STZ injection. (e) Urine albumin-to-creatinine ratio (ACR) and (f) creatinine clearance rate (Ccr) were measured before and after WJ-39 treatment (14 weeks and 26 weeks after STZ administration, respectively). (g) Representative images (400×) and mesangial matrix index of periodic acid-Schiff (PAS) staining of DN rat kidneys with different treatments (, ). (h) Representative images (400×) and percentage of fibrosis of Masson’s trichrome staining of DN rat kidneys with different treatments (, ). (i) Representative images showing the changes in glomerular basement membrane thickening and podocytic processes are marked with arrows (). A: control; B: DN rats; C, D, and E: DN rats treated with WJ-39 (10, 20, and 40 mg/kg); F: DN rats treated with irbesartan (30 mg/kg); G: DN rats treated with epalrestat (15 mg/kg). Data are represented as the (SEM), . ^## and ^### vs. the control group; , , and vs. the STZ group; ^$$ vs. the STZ group at 14 weeks; ^& and ^&& vs. the group (STZ+WJ-39 40 mg/kg) before treatment.

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