Rosuvastatin Induces Renal HO-1 Activity and Expression Levels as a Main Protective Mechanism against STZ-Induced Diabetic Nephropathy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Drugs and Chemicals
2.2. Animal Protocol and Experimental Design
2.3. Biochemical Analysis
2.4. Renal Histopathology
2.5. Western Blot Assay
2.6. HO-1 Activity Assay Method
2.7. Statistical Analysis
3. Results
3.1. The Effect on Weight and Blood Glucose Levels
3.2. The Effect on Biochemical Kidney Function Parameters and Serum Lipid Profile
3.3. The Effect on Renal Histopathology
3.4. The Effect on Renal Oxidative Stress Markers
3.5. The Effect on Renal HO-1 Expression and Activity
3.6. The Effect on Renal TNF-α and Caspase 3 Expression
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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% ∆ Body Weight | Kidney Index | Blood Glucose at 0-Time (mg/dL) | Blood Glucose at Day 60 (mg/dL) | |
---|---|---|---|---|
Control | 134 ± 3 | 0.52 ± 0.02 | 126 ± 3 | 148 ± 6 |
RSV | 135 ± 2 | 0.5 ± 0.04 | 128 ± 8 | 112 ± 10 |
DN | 85 ± 1 a | 1.0 ± 0.05 a | 542 ± 63 a | 464 ± 70 a |
DN/RSV | 103 ± 1 a,b | 0.59 ± 0.03 b | 504 ± 41 a | 462 ± 49 a |
DN/RSV/ZnPP | 88 ± 2 a,c | 0.85 ± 0.05 a,c | 458 ± 79 a | 538 ± 29 a |
Control | RSV | DN | DN/RSV | DN/RSV/ZnPP | |
---|---|---|---|---|---|
Serum Urea (mg/dL) | 11 ± 1 | 10 ± 1 | 24 ± 1 a | 12 ± 2 b | 28 ± 1 a,c |
Serum Creatinine (mg/dL) | 0.89 ± 0.10 | 0.98 ± 0.08 | 4.00 ± 0.13 a | 1.2 ± 0.06 b | 3.6 ± 0.29 a,c |
Serum Albumin (g/dL) | 3.4 ± 0.3 | 3.1 ± 0.2 | 2.0 ± 0.1 a | 3.2 ± 0.2 b | 2.2 ± 0.1 a,c |
ACR (mg/g) | 17 ± 1 | 13 ± 1 | 193 ± 23 a | 69 ± 10 b | 187 ± 18 a,c |
Serum Na+ (mEq/L) | 134 ± 2 | 133 ± 12 | 210 ± 5 a | 145 ± 6 b | 230 ± 18 a,c |
Urine Na+ (mEq/L) | 937 ± 24 | 1063 ± 46 | 393 ± 23 a | 863 ± 75 b | 532 ± 6 a,c |
Serum K+ (mEq/L) | 3.4 ± 0.2 | 4.1 ± 0.2 | 7.6 ± 0.5 a | 4.6 ± 0.3 b | 6.3 ± 0.3 a |
Urine K+ (mEq/L) | 89 ± 6 | 83 ± 5 | 22 ± 1 a | 44 ± 5 a,b | 27.8 ± 1.9 a |
Total Cholesterol (mg/dL) | Triglycerides (mg/dL) | HDL-C (mg/dL) | LDL-C (mg/dL) | |
---|---|---|---|---|
Control | 70 ± 1 | 36.6 ± 0.5 | 50 ± 3 | 14 ± 2 |
RSV | 70 ± 3 | 36.0 ± 0.3 | 51 ± 3 | 14 ± 1 |
DN | 79 ± 2 a | 49.3 ± 1.9 a | 22 ± 3 a | 45 ± 2 a |
DN/RSV | 63 ± 2 b | 36.1 ± 1.6 b | 50 ± 2 b | 23 ± 2 b |
DN/RSV/ZnPP | 64 ± 2 b | 38.9 ± 1.7 b | 45 ± 4 b | 22 ± 2 b |
Tubular Degeneration | Tubular Dilation | Congested Blood Vessels | Leukocytic Infiltration | Vacuolation of Lining Epithelium | Congestion of Glomerular Tuft | |
---|---|---|---|---|---|---|
Control | - | - | - | - | - | - |
RSV | - | - | - | - | - | - |
DN | ++ | ++ | +++ | +++ | +++ | +++ |
DN/RSV | - | + | + | + | + | + |
DN/RSV/ZNPP | ++ | + | ++ | +++ | ++ | ++ |
GSH (mmol/g Tissue) | SOD (U/g Tissue) | Catalase (U/g Tissue) | MDA (nmol/g Tissue) | MPO (U/g Tissue) | NO (nmol/g Tissue) | |
---|---|---|---|---|---|---|
Control | 56 ± 3 | 1199 ± 62 | 433 ± 11 | 200 ± 3 | 0.12 ± 0.02 | 112 ± 3 |
RSV | 50 ± 4 | 1138 ± 80 | 397 ± 14 | 189 ± 4 | 0.11 ± 0.02 | 124 ± 10 |
DN | 29 ± 2 a | 629 ± 70 a | 135 ± 19 a | 352 ± 8 a | 0.32 ± 0.04 a | 264 ± 8 a |
DN/RSV | 48 ± 2 b | 1131 ± 73 b | 320 ± 21 a,b | 305 ± 10 a,b | 0.17 ± 0.01 b | 131 ± 9 b |
DN/RSV/ZNPP | 32 ± 2 a,c | 451 ± 52 a,c | 198 ± 20 a,c | 361 ± 8 a,c | 0.30 ± 0.04 a,c | 248 ± 24 a,c |
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Heeba, G.H.; Ali, M.A.M.; El-Sheikh, A.A.K. Rosuvastatin Induces Renal HO-1 Activity and Expression Levels as a Main Protective Mechanism against STZ-Induced Diabetic Nephropathy. Medicina 2022, 58, 425. https://doi.org/10.3390/medicina58030425
Heeba GH, Ali MAM, El-Sheikh AAK. Rosuvastatin Induces Renal HO-1 Activity and Expression Levels as a Main Protective Mechanism against STZ-Induced Diabetic Nephropathy. Medicina. 2022; 58(3):425. https://doi.org/10.3390/medicina58030425
Chicago/Turabian StyleHeeba, Gehan H., Marwa A. M. Ali, and Azza A. K. El-Sheikh. 2022. "Rosuvastatin Induces Renal HO-1 Activity and Expression Levels as a Main Protective Mechanism against STZ-Induced Diabetic Nephropathy" Medicina 58, no. 3: 425. https://doi.org/10.3390/medicina58030425