Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

Betz, Boris; Schneider, Reinhard; Kress, Tobias T.; Schick, Martin Alexander; Wanner, Christoph; Sauvant, Christoph

doi:10.1155/2012/219319

Cited by 35 publications

(26 citation statements)

References 39 publications

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“…The present results were consistent with other experimental studies that demonstrated that TZDs are beneficial for renal and cardiovascular protection (13,18,22,23). ROG intervention attenuated hyperuricemia, which is generally acknowledged as an independent risk factor of CKD.…”

Section: Discussionsupporting

confidence: 93%

Rosiglitazone alleviates injury in rats with adenine-induced chronic kidney disease

Huang

Yan

Zheng

et al. 2013

Molecular Medicine Reports

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Abstract. Rosiglitazone (ROG) has been shown to exert beneficial effects on glycemic control and renal protection. Circulatory fibroblast growth factor-23 (FGF-23) is a novel independent risk factor for chronic kidney disease (CKD) progression. The current study focused on how ROG impacts on injury of the kidney, and whether FGF-23 is involved in the process. A total of 24 male Sprague Dawley rats, weighing 250-280 g, were divided into four groups (n=6 per group): i) Normal; ii) ROG controls, treated with ROG (10 mg/kg/day); iii) CKD models, treated with adenine (200 mg/kg/day); and iv) ROG treatment, treated with ROG (10 mg/kg/day) and adenine (200 mg/kg/day). The rats were sacrificed after four weeks, and serum, urine and kidney tissues were collected. The data revealed that the serum levels of inorganic phosphate (Pi), intact parathyroid hormone (iPTH) and FGF-23 were significantly higher in the CKD models compared with those in the normal group (P<0.01), while ROG significantly reduced the serum levels of Pi, iPTH and FGF-23 (P<0.01). The ratio of protein/creatine (Cr) in the urine and the serum levels of Cr, blood urea nitrogen and uric acid were significantly increased in the CKD models compared with the normal group (P<0.01), however, ROG significantly reduced these parameters (P<0.05). Furthermore, ROG significantly alleviated the tubule interstitial damage index of the CKD models in comparison with that of the controls. These results indicated that ROG mitigates the lesions of chronic kidney disease induced by adenine, and that the system of Pi-PTH-FGF-23 may contribute to this process. The possible mechanisms underlying this process require confirmation in future studies.

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Section: Discussionsupporting

confidence: 93%

Rosiglitazone alleviates injury in rats with adenine-induced chronic kidney disease

Huang

Yan

Zheng

et al. 2013

Molecular Medicine Reports

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“…18,25 After treatment with NGAL, rats showed down-regulated Cc3 protein compared with I/R þ NS rats. Caspases are intracellular proteases family that regulate programmed cell death, and the activation of the caspase family is a key part in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Gelatinase-Associated Lipocalin (NGAL) May Play a Protective Role Against Rats Ischemia/Reperfusion Renal Injury via Inhibiting Tubular Epithelial Cell Apoptosis

Zang

Wang

et al. 2012

Renal Failure

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We investigated the protective effect and mechanism of neutrophil gelatinase-associated lipocalin (NGAL) on rats ischemia/reperfusion (I/R) renal injury. Eighteen Sprague-Dawley male rats were randomly divided into three groups. Control group (n ¼ 6) suffered left unilateral nephrectomy, I/R þ NS (normal saline) (n ¼ 6) and I/R þ NGAL (n ¼ 6) group were subjected to 45 min right renal ischemia/24 h reperfusion after left unilateral nephrectomy. Serum creatinine (Scr) and blood urea nitrogen (Bun) were measured on automatic biochemistry analyzer; kidney sections were stained with hematoxylin-eosin; terminal dUTP nick-labeling method was used to examine the apoptosis of tubular epithelial cells; Cleaved caspase-3 and Bax protein expression were detected by immunohistochemistry and Western Blot; real-time polymerase chain reaction was used to detect the expression of Bax mRNA. Rats with NGAL displayed an attenuated renal damage and a decreased number of tubular epithelial cell apoptosis compared to the I/R þ NS group (Scr 63.400 AE 11.908 vs. 121.857 AE 17.151 μmol/L, Bun 14.840 AE 2.868 vs. 28.557 AE 6.434 mmol/L, apoptosis cell number 7.800 AE 1.924 vs. 15.400 AE 3.049/high power field (HPF), p < 0.05), the values were lower in the control group (24.000 AE 3.829 μmol/L, 5.814 AE 1.961 mmol/L, 1.800 AE 0.837/HPF, p < 0.05) compared to two groups above; NGALtreated rats showed down-regulated Cleaved caspase-3 protein (0.284 AE 0.066 vs. 0.409 AE 0.073, p < 0.05), Bax protein (0.346 AE 0.055 vs. 0.443 AE 0.041, p < 0.05), Bax mRNA (1.423 AE 0.187 vs. 2.550 AE 0.217, p < 0.05) compared to I/R þ NS group, but the values were higher in both of the two groups than those in the control group (Cleaved caspase-3 protein 0.104 AE 0.029, Bax protein 0.155 AE 0.027, Bax mRNA 1.000 AE 0.000, p < 0.05). We supposed that exogenous NGAL can inhibit the activation of caspase-3, reduce the expression of Bax, and thus reduce renal tubular cell apoptosis and protect renal function in I/R injury rats.

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“…PCR amplification protocol and primers were used as recently described [2,7,8] Quantification was performed using the ΔΔC T method using β-actin as reference gene and expression in control cells was normalized to 1.…”

Section: Methodsmentioning

confidence: 99%

“…The organic anion transport system of the renal proximal tubule plays a crucial role in the excretion of a variety of potentially toxic compounds [1,2,3,4,5,6,7,8,9,10]. This system consists of organic anion exchangers located at the basolateral membrane that represent the rate determining step of elimination and the efflux step through the apical membrane [11,12].…”

Section: Introductionmentioning

confidence: 99%

Differential Effect of COX1 and COX2 Inhibitors on Renal Outcomes following Ischemic Acute Kidney Injury

et al. 2014

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Background/Aims: We have previously shown that 1 mg/kg indomethacin improves expression and functionality of renal organic anion transporters Oat1 and Oat3 after renal ischemia and furthermore improves renal outcome after ischemia. As we detected differential effects of COX1 or COX2 inhibitors on organic anion transport after ischemia and reperfusion in culture, we investigated the effect of the SC560 (COX1 inhibitor) and SC58125 (COX2 inhibitor) on expression of Oat1/3 and renal outcome after ischemic acute kidney injury (iAKI). Methods: iAKI was induced in rats by bilateral clamping of renal arteries for 45 min. SC560 or SC58125 (1 mg/kg each) were given intraperitoneally as soon as reperfusion started. Sham-treated animals served as controls. Oat1/3 were determined by qPCR and Western blot. Glomerular filtration rate (GFR), p-aminohippurate (PAH) clearance and PAH extraction ratio was determined. All parameters were detected 24 h after ischemia. Renal plasma flow was calculated. Results: In clamped animals SC560 (COX1 inhibitor) restored expression of Oat1/3, as well as renal perfusion. Additionally, SC560 substantially improved kidney function as measured by GFR. Application of the COX2 inhibitor SC58125 did not exert these beneficial effects. Conclusion: Our study indicates that COX1 inhibitor SC560 applied after ischemia prevents ischemia-induced downregulation of Oat1/3 during reperfusion and has a substantial protective effect on kidney function. Whether and to what particular extent this apparent improvement of function is mechanistically due to beneficial effects on tubular function, renal perfusion or glomerular filtration will be the scope of future studies.

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Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

Cited by 35 publications

References 39 publications

Rosiglitazone alleviates injury in rats with adenine-induced chronic kidney disease

Rosiglitazone alleviates injury in rats with adenine-induced chronic kidney disease

Neutrophil Gelatinase-Associated Lipocalin (NGAL) May Play a Protective Role Against Rats Ischemia/Reperfusion Renal Injury via Inhibiting Tubular Epithelial Cell Apoptosis

Differential Effect of COX1 and COX2 Inhibitors on Renal Outcomes following Ischemic Acute Kidney Injury

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