J Korean Soc Hypertens.  2013 Dec;19(4):123-131. 10.5646/jksh.2013.19.4.123.

Effects of Tamoxifen in Deoxycorticosterone Acetate-salt Hypertensive Nephropahty

• Choi JS
• Kim IJ
• Kim CS
• Bae EH
• Ma SK
• Lee JU
• Kim SW

• KMID: 1838116
• DOI: http://doi.org/10.5646/jksh.2013.19.4.123

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-beta (TGF-beta), Smad, alpha-smooth muscle actin (alpha-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-alpha (TNF-alpha), 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-beta, Smad 2/3, Smad 4, alpha-SMA, ED-1, COX-2, iNOS was increased compared with controls, and these changes were attenuated by tamoxifen treatment except that of TGF-beta. The mRNA expression of TNF-alpha, MCP-1, and VCAM-1 was increased, and expression of MCP-1 and VCAM-1 was counteracted by tamoxifen treatment.
CONCLUSIONS
Tamoxifen is effective in preventing the progression of nephropathy in DSH rats, the mechanism of which is associated with anti-inflammation and anti-fibrotic effects.

Keyword

Desoxycorticosterone acetate; Hypertension; Tamoxifen

MeSH Terms

Actins
Animals
Blood Pressure
Cadherins
Chemokine CCL2
Creatinine
Cyclooxygenase 2
Desoxycorticosterone Acetate
Desoxycorticosterone*
Fibrosis
Humans
Hypertension
Immunoblotting
Inflammation
Kidney
Male
Methods
Muscles
Nephrectomy
Nitric Oxide Synthase Type II
Rats
Rats, Sprague-Dawley
Real-Time Polymerase Chain Reaction
RNA, Messenger
Tamoxifen*
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1
Actins
Cadherins
Chemokine CCL2
Creatinine
Cyclooxygenase 2
Desoxycorticosterone
Nitric Oxide Synthase Type II
RNA, Messenger
Tamoxifen
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha
Vascular Cell Adhesion Molecule-1

Figure

• 

  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.

Reference

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