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ABSTRACT
Background:
The present study was designed to evaluate the possible renoprotective effects of tamoxifen in deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats and its role in inflammation and fibrosis in the kidney.
Methods:
Male Sprague-Dawley rats, weighing 180 to 200 g, were used. All rats underwent unilateral nephrectomy. One week later, one group of rats (n = 8) was implanted with DOCA strips (200 mg/kg) and another group of rats (n = 8) was implanted with DOCA strips with co-treated with tamoxifen (10 mg/kg) through gavage feeding. Rats that did not implanted DOCA strips served as controls (n = 6). Two weeks later, the systolic blood pressure (SBP) was measured by tail-cuff method. The protein expression of transforming growth factor-β (TGF-β), Smad, -smooth muscle actin (α-SMA), E-cadherin, ED-1, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) was determined in the kidney by immunoblotting. The mRNA expression of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1) was determined by real-time polymerase chain reaction.
Results:
In DSH rats, SBP was increased, which was not affected by tamoxifen treatment. Serum creatinine level was comparable in DSH rats compared with controls, which was not affected by tamoxifen treatment. In DSH rats, the protein expression of TGF-β, Smad 2/3, Smad 4, -SMA, ED-1, COX-2, iNOS was increased compared with controls, and these changes were attenuated by tamoxifen treatment except that of TGF-β. The mRNA expression of TNF-α, MCP-1, and VCAM-1 was increased, and expression of MCP-1 and VCAM-1 was counteracted α by tamoxifen treatment.
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Fig. 1.
Effect of tamoxifen on transforming growth factor (TGF)-β1 and Smad proteins in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Semiquantitative immunoblotting for TGF-b1 and Smad 2/3, Smad 4, and Smad 6 proteins. *p < 0.05 compared ＜ to the control. † p 0.05 compared to DOCA-salt hypertensive rats. DOCA, DOCA-salt hypertensive rats; D + tamoxifen, tamoxifen treated DOCA-salt hypertensive rats.
Fig. 2.
Effect of tamoxifen on α-smooth muscle actin (α-SMA) and E-cadherin in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Semiquantitative immunoblotting for α-SMA and E-cadherin proteins. *p < 0.05 compared to the control. †p < 0.05 compared to DOCA-salt hypertensive rats. DOCA, DOCA-salt hypertensive rats; D + tamoxifen, tamoxifen treated DOCA-salt hypertensive rats.
Fig. 3.
Effect of tamoxifen on inflammation in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Semiquantitative immunoblotting for ED-1, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. *p < 0.05 compared to the control. †p < 0.05 compared to DOCA-salt hypertensive rats. DOCA, DOCA-salt hypertensive rats; D + tamoxifen, tamoxifen treated DOCA-salt hypertensive rats.
Fig. 4.
mRNA expression of tumor necrosis factor- (TNF α - ), monocyte chemotactic protein α -1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) in DOCA-salt hypertensive rats. Columns show real time polymerase chain reaction data. *p < 0.05 compared to the control. †p < 0.05 compared to DOCA-salt hypertensive rats. DOCA, DOCA-salt hypertensive rats; D + tamoxifen, tamoxifen treated DOCA-salt hypertensive rats.
Table 1.
Organ weights, blood pressure and renal function
| Control (n = 6) | DSH (n = 8) | DSH + tamoxifen (n = 8) | |
|---|---|---|---|
| Body weight (g) | 224.2 ± 4.9 | 231.3 ± 12.5 | 218.8 ± 12.5* |
| Systolic blood pressure (mm Hg) | 130.1 ± 5.2 | 173.5 ± 6.2† | 170.7 ± 12.0‡ |
| Kidney weight (mg) | 1238 ± 81 | 1748 ± 259† | 1650 ± 459‡ |
| Kidney weight/body weight ratio (mg/g) | 5.5 ± 0.3 | 7.5 ± 0.9† | 7.5 ± 1.8‡ |
| Blood urea nitrogen (mg/dL) | 13.6 ± 1.0 | 14.7 ± 2.7 | 14.8 ± 1.6 |
| Creatinine (mg/dL) | 0.27 ± 0.08 | 0.24 ± 0.05 | 0.27 ± 0.05 |
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