In:
American Journal of Nephrology, S. Karger AG, Vol. 37, No. 1 ( 2013), p. 7-15
Abstract:
〈 b 〉 〈 i 〉 Background/Aim: 〈 /i 〉 〈 /b 〉 Cyclosporine (CsA)-induced kidney injury is characterized by renal dysfunction with inflammatory cell infiltrations, apoptosis and fibrosis. Pleiotropic effects of statins may exert anti-inflammatory, antiapoptotic and antifibrotic actions beyond lipid control. The aim of this study is to investigate whether rosuvastatin (RUS) has anti-inflammatory, antiapoptotic and antifibrotic effects on chronic CsA-induced nephropathy in a rat model. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Male Sprague-Dawley rats fed a low-sodium diet were divided into three treatment groups: control (0.9% saline injection), CsA (15 mg/kg/day by subcutaneous injection), CsA + RUS (10 mg/kg/day by gastric gavage). Renal function, CsA level and lipid levels were measured at the end of 4 weeks. The expression of ED-1, transforming growth factor-β 〈 sub 〉 1 〈 /sub 〉 (TGF-β 〈 sub 〉 1 〈 /sub 〉 ) and α-smooth muscle actin (α-SMA) for inflammation and fibrosis were examined by Western blot analysis. The expression levels of apoptosis-associated factors were examined by Western blot analysis. Apoptosis was evaluated using the terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling (TUNEL) method. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Kidney function was decreased in CsA-treated rats compared with controls, which was attenuated by RUS. RUS did not affect the lipid level or the blood CsA level. TUNEL staining showed that RUS inhibited CsA-induced tubular apoptosis. RUS decreased CsA-induced increased expression of Bax/Bcl-2 ratio. The expressions of ED-1, α-SMA, TGF-β 〈 sub 〉 1 〈 /sub 〉 , Smad2/3, Smad4 and p-JNK were increased in CsA-treated rats, which were attenuated by RUS. Tubular atrophy and interstitial fibrosis in CsA-treated rats were attenuated by RUS supplementation. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 RUS supplementation attenuates proinflammatory and apoptosis-related factors and inhibits the fibrotic pathways including the smad-dependent and smad-independent pathways in a rat model of CsA-induced nephropathy.
Type of Medium:
Online Resource
ISSN:
0250-8095
,
1421-9670
Language:
English
Publisher:
S. Karger AG
Publication Date:
2013
detail.hit.zdb_id:
1468523-1
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