Effects of Tamoxifen in Deoxycorticosterone Acetate-salt Hypertensive Nephropahty.
10.5646/jksh.2013.19.4.123
- Author:
Joon Seok CHOI
1
;
In Jin KIM
;
Chang Seong KIM
;
Eun Hui BAE
;
Seong Kwon MA
;
Jong Un LEE
;
Soo Wan KIM
Author Information
1. Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. skimw@chonnam.ac.kr
- Publication Type:Original Article
- Keywords:
Desoxycorticosterone acetate;
Hypertension;
Tamoxifen
- MeSH:
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
- From:Journal of the Korean Society of Hypertension
2013;19(4):123-131
- CountryRepublic of Korea
- Language:Korean
-
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.
