Reduction of the Accumulation of Advanced Glycation End Products by ACE Inhibition in Experimental Diabetic Nephropathy
Article Figures & Tables
Figures
- FIG. 1.
Albumin excretion over 24 h at week 12. Data are expressed as geometric mean ×/÷ tolerance factor. *P < 0.005 vs. control; †P < 0.001, ‡P < 0.05 vs. diabetic. Cont, control; C+ACEi, control plus ACEI; C+AG, control plus aminoguanidine; Diab, diabetic; D+ACEi, diabetic plus ACEI; D+AG, diabetic plus aminoguanidine.
- FIG. 2.
A: Renal AGE fluorescence at 370/440 nm corrected for protein content. *P < 0.001 vs. diabetic; †P < 0.05 vs. control. B: Morphometric analysis of immunostaining for renal AGEs. *P < 0.001 for control vs. diabetic; †P < 0.01 vs. diabetic. C, control; C+ACEi, control plus ACEI; C+AG, control plus aminoguanidine; D, diabetic; D+ACEi, diabetic plus ACEI; D+AG, diabetic plus aminoguanidine.
- FIG. 3.
Immunohistochemical staining for renal AGEs at week 12. A: Control kidney; B: Diabetic kidney; C: Diabetic kidney plus ACE inhibition; D: negative control kidney. Magnification ×400.
- FIG. 4.
Morphometric analysis of immunostaining for renal RAGE at week 12. *P < 0.001 vs. control; †P = 0.07 vs. diabetic. Cont, control; C+ACEi, control plus ACEI; C+AG, control plus aminoguanidine; Diab, diabetic; D+ACEi, diabetic plus ACEI; D+AG, diabetic plus aminoguanidine.
- FIG. 5.
A: Morphometric analysis of immunostaining for glomerular nitrotyrosine at week 12. *P < 0.005 vs. control; †P < 0.001 vs. diabetic. B: Morphometric analysis of immunostaining for tubular nitrotyrosine at week 12. *P < 0.001 vs. diabetic; †P < 0.001 vs. control; ‡P < 0.01 vs. control plus ACEI. Cont, control; C+ACEi, control plus ACEI; C+AG, control plus aminoguanidine; Diab, diabetic; D+ACEi, diabetic plus ACEI; D+AG, diabetic plus aminoguanidine.
- FIG. 6.
Immunohistochemical staining for renal nitrotyrosine (A), control kidney (B), diabetic kidney (C), and diabetic kidney plus ACE inhibition (D). Magnification ×400.
- FIG. 7.
A: Representative EMSA acrylamide gel pictured for all groups at 12 weeks. B: Quantitation of activated NF-κB by EMSA. *P < 0.05 vs. control group. Cont, control; Diab, diabetic; C+AG, control plus aminoguanidine; D+AG, diabetic plus aminoguanidine; C+ACEi, control plus ACEI; D+ACEi, diabetic plus ACEI.
Tables
- TABLE 1
Biochemical and metabolic parameters for all animals at week 12
Control Control plus ACEI Control plus AG Diabetic Diabetic plus ACEI Diabetic plus AG n 6 6 6 6 6 6 Glucose (mmol/l) 5.4 ± 0.2 5.8 ± 0.2 5.6 ± 0.2 22.1 ± 1.7* 18.4 ± 2.0* 21.4 ± 1.5* HbA1c (%) 3.6 ± 0.2 3.3 ± 0.6 3.9 ± 0.2 10.6 ± 0.4* 9.1 ± 0.7* 9.7 ± 0.5* Body weight (g) 453 ± 8 402 ± 17 420 ± 12 302 ± 15* 314 ± 22* 341 ± 22* Kidney-to-body weight ratio (×10−3) 6.4 ± 0.3 7.1 ± 0.2 6.6 ± 0.1 10.7 ± 0.4* 10.0 ± 0.0* 10.7 ± 0.0* GFR (ml/min) 3.2 ± 0.2 3.3 ± 0.2 3.2 ± 0.1 3.9 ± 0.2† 3.5 ± 0.3 4.1 ± 0.2* Urine volume (ml/24 h) 15 ± 1 22 ± 2 25 ± 2 121 ± 12* 76 ± 14* 107 ± 16* Blood pressure (mmHg) 133 ± 3 130 ± 7 140 ± 5 147 ± 3 129 ± 7‡ 144 ± 5 Serum AGEs 8.7 ± 0.6 8.3 ± 0.6 7.7 ± 0.6 11.6 ± 0.4* 8.3 ± 0.6‡ 8.7 ± 0.5‡ * P < 0.005;
† P < 0.02 vs. appropriate control;
‡ P < 0.05 vs. diabetic. AG, aminoguanidine.
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