Antioxidant and renoprotective effects of paricalcitol on experimental contrast-induced nephropathy model

Arı, Elif; Kedrah, Alla Elden; Alahdab, Yeşim Özen; Bulut, Gülay; Eren, Zehra; Baytekin, Özlem; Odabaşı, Dolunay

doi:10.1259/bjr/16327485

Cited by 40 publications

(21 citation statements)

References 26 publications

(37 reference statements)

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“…Oxidative stress refers to the imbalance between the antioxidative defense system and the oxidative system [26,27]. Recently, it is documented that paricalcitol has not only renin inhibitor effects, but also antioxidant effects [12,28,29,30]. Izquierdo et al reported that paricalcitol decreases serum MDA levels and increases serum GSH, thioredoxin, catalase and SOD activities in hemodialysis patients [29].…”

Section: Discussionmentioning

confidence: 99%

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

Eren

Günal

Bakır

et al. 2014

Kidney Blood Press Res

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Background/Aims: 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. Methods: 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. Results: 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). Conclusion: 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.

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Section: Discussionmentioning

confidence: 99%

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

Eren

Günal

Bakır

et al. 2014

Kidney Blood Press Res

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“…Histological sections were evaluated by a board-certified veterinary pathologist who was blinded to the experimental groups at the time of evaluation. Histological alterations were evaluated by a modification of a previously described scoring system for evaluation of CIAKI [37] . This consisted of assessment for tubular damage and protein casts according to the following key: 0, no alterations; 1, mild, isolated foci, <5% tubules affected; 2, moderate, 5–25% tubules affected; 3, marked, 26–50% tubules affected; 4, severe, >50% tubules affected.…”

Section: Methodsmentioning

confidence: 99%

Sildenafil Citrate for Prophylaxis of Nephropathy in an Animal Model of Contrast-Induced Acute Kidney Injury

et al. 2014

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Contrast-induced acute kidney injury (CIAKI) is one of the commonest complications associated with contrast media (CM). Although the exact etiology of CIAKI remains unclear, one hypothesis involves vasoconstriction of afferent arterioles resulting in renal ischemia. Increased renal blood flow, therefore, might represent an attractive target for the treatment of CIAKI. In this study we evaluated the protective effects of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate, in a rabbit model of CIAKI. New Zealand white rabbits were used due to their susceptibility to CIAKI. To evaluate the effects of sildenafil, the drug was administered before CM infusion and repeatedly throughout the remainder of the experiment (6 mg/kg, p.o.). Animals were sacrificed after 48 hours and kidneys were prepared for histological evaluation. Intravenous administration of CM produced marked kidney injury. Serum creatinine concentrations were elevated within two hours of the infusion and remained elevated for the duration of the experiment. Histological evaluation of the kidneys revealed significant tubular necrosis. The effects of the CM were dose dependent. Treatment with sildenafil was associated with lesser degree of histological injury, attenuation in markers of acute kidney injury (48 hour creatinine 1.54±0.21 versus 4.42±1.31 mg/dl, p<0.05) and reduction in electrolyte derangement (percent change in serum K+ at 48 hours 2.55±3.80% versus 15.53±4.47%, p<0.05; serum Na+ at 48 hours −0.14±0.26% versus −1.97±1.29%, p = 0.20). The results suggest a possible role for PDE5 inhibitors in the treatment of CIAKI and warrant further evaluation to determine the exact mechanism of protection.

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“…In a rat model of amikacin-induced nephrotoxicity, renal tissue MDA levels were significantly lower, and SOD and glutathione peroxidase activities in the kidney were significantly higher when rats were treated with paricalcitol [ 29 ]. Other reports have also proven the effects of paricalcitol on renal oxidative stress biomarkers, such as thiobarbituric acid-reactive substrates and 8-hydroxy-2′-deoxyguanosine, in models of contrast- or cyclosporine-induced nephropathy [ 30 – 31 ]. However, a previous study using a combined aliskiren and paricalcitol treatment showed no increased effect on oxidative stress of kidneys in a streptozotocin-induced diabetic model over that of either agent alone [ 32 ]; these results are consistent with our current findings in UUO.…”

Section: Discussionmentioning

confidence: 99%

Treatment combining aliskiren with paricalcitol is effective against progressive renal tubulointerstitial fibrosis via dual blockade of intrarenal renin

Chung

Kim

et al. 2017

PLoS ONE

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The aim of this study was to assess any potential additive effects of a treatment combining aliskiren with paricalcitol on reducing renal fibrosis. C57BL/6J mice were treated individually with aliskiren and/or paricalcitol until 7 days after initiation of unilateral ureteral obstruction (UUO).In obstructed kidneys of UUO mice, monotherapy with aliskiren or paricalcitol significantly attenuated interstitial fibrosis, collagen IV accumulation, and α-smooth muscle actin- and terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling-positive cells. The combination treatment showed additive efficacy in inhibition of these parameters. Renal NADPH oxidase (Nox)1 and Nox2 were significantly decreased by aliskiren or paricalcitol alone or in combination, while renal Nox4 expression was significantly reduced by paricalcitol mono- or combination treatment. Increased levels of p-Erk and p-p38 MAPK, and NF-κB in UUO kidneys were also significantly reduced by either aliskiren or paricalcitol treatment alone or in combination. Aliskiren or paricalcitol monotherapy significantly reduced the expression of (pro)renin receptor in UUO kidneys. In addition, aliskiren tended to augment renin expression in UUO kidneys, but paricalcitol reduced its expression level. The combination treatment effectively blocked both (pro)renin receptor and renin expression induced by aliskiren, and resulted in a further reduction of the renal expression of angiotensin II AT1 receptor. Aliskiren failed to increase the expression of vitamin D receptor in UUO kidneys, but the combination treatment restored its expression level. Taken together, a treatment combining aliskiren with paricalcitol better inhibits UUO-induced renal injury. The mechanism of this synergy may involve more profound inhibition of the intrarenal renin-angiotensin system.

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Antioxidant and renoprotective effects of paricalcitol on experimental contrast-induced nephropathy model

Cited by 40 publications

References 26 publications

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

Effects of Paricalcitol and Aliskiren Combination Therapy on Experimental Diabetic Nephropathy Model in Rats

Sildenafil Citrate for Prophylaxis of Nephropathy in an Animal Model of Contrast-Induced Acute Kidney Injury

Treatment combining aliskiren with paricalcitol is effective against progressive renal tubulointerstitial fibrosis via dual blockade of intrarenal renin

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