In:
Kidney and Blood Pressure Research, S. Karger AG, Vol. 39, No. 6 ( 2014), p. 581-590
Abstract:
〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 The aim of the present study was to investigate the effect of combination of aliskiren with paricalcitol on experimental diabetic nephropathy (DN) model in rats. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Forty male Sprague Dawley rats were divided into 5 groups of 8 rats each, namely the control (Group C), diabetes (Group D), aliskiren (Group A), paricalcitol (Group P), and aliskiren plus paricalcitol (Group A+P) groups. Aliskiren was given by oral-gavage at a dose of 50 mg/kg/day once daily for 12 weeks. Paricalcitol was given by intraperitoneally at a dose of 0,4 µg/kg/three day of week for 12 weeks. Renal function parameters, oxidative stress biomarkers, mRNA expression of renin-angiotensin system parameters and kidney histology were determined. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Group A+P had lower mean albümin-to-creatinine ratio (ACR) (p=0.004) as well as higher creatinine clearance (CCr) (p 〈 0.005) than the diabetic rats (Group D). Combination therapy significantly increased CCr (Group A+P vs Group A, p 〈 0.005; Group A+P vs Group P, p=0.022) and reduced ACR (Group A+P vs Group A, p=0.018; Group A+P vs Group P, p 〈 0.005) when compared to monotherapy. Serum malondialdehyde levels were significantly lower (p=0.004); glutathion levels (p=0.003), glutathion peroxidase (p=0.004) and superoxide dismutase (p 〈 0.005) activities were significantly higher in group A+P than in group D. The mean scores of mRNA expression of renin (p 〈 0.005), angiotensin II (p=0.012) and angiotensin type 1 receptor (p=0.018) in group A+P were significantly lower. Although combination therapy showed no additional effect on oxidative system, renin-angiotensin system and renal histology, aliskiren plus paricalcitol significantly decreased interstitial fibrosis volume when compared to monotherapy (Group A+P vs Group A, p 〈 0.005; Group A+P vs Group P, p=0.002). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our data seem to suggest a potential role of aliskiren plus paricalcitol acting synergystically for reducing the progression of diabetic nephropathy in an experimental rat model.
Type of Medium:
Online Resource
ISSN:
1420-4096
,
1423-0143
Language:
English
Publisher:
S. Karger AG
Publication Date:
2014
detail.hit.zdb_id:
1482922-8
