The effects of PPAR-γ agonist pioglitazone on renal ischemia/reperfusion injury in rats

Reel, Buket; Guzeloglu, Mehmet; Bağrıyanık, Alper; Atmaca, Soner; Aykut, Koray; Albayrak, Gökhan; Hazan, E

doi:10.1016/j.jss.2012.08.020

Cited by 56 publications

(30 citation statements)

References 47 publications

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“…We found that TIMP-1 and TIMP-2 levels decreased signifi cantly during renal I-R. LA pretreatment, however, increased TIMPs during renal I-R. Knugi et al (2011) reported that both TIMP-2 and TIMP-1 decreased, by contrast to MMP-2 and MMP-9, which increased during renal I-R. Caron et al (2005b) showed that the TIMP-1 level decreased during ischemia. Basil et al (2004) and Reel et al (2013), however, reported that both TIMP-1 and TIMP-2 were increased in a renal I-R model.…”

Section: Discussionmentioning

confidence: 98%

The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model

Cavdar¹,

Özbal²,

Celik³

et al. 2013

Biotechnic & Histochemistry

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Matrix metalloproteinases (MMPs) are enzymes that are responsible for degradation of extracellular matrix (ECM); they are involved in the pathogenesis of ischemia-re-perfusion (I-R) injury. We investigated the possible preventive effect of alpha-lipoic acid (LA) in a renal I-R injury model in rats by assessing its reducing effect on the expression and activation of MMP-2 and MMP-9 induced by I-R. Rats were assigned to four groups: control, sham-operated, I-R (saline, i.p.) and I-R+ LA (100 mg/kg, i.p.). After a right nephrectomy, I-R was induced by clamping the left renal pedicle for 1 h, followed by 6 h re-perfusion. In the sham group, a right nephrectomy was performed and left renal pedicles were dissected without clamping and the entire left kidney was excised after 6 h. LA pretreatment was started 30 min prior to induction of ischemia. Injury to tubules was evaluated using light and electron microscopy. The expressions of MMP-2 and MMP-9 were determined by immunohistochemistry and their activities were analyzed by gelatin zymography. Serum creatinine was measured using a quantitative kit based on the Jaffe colorimetric technique. Malondialdehyde (MDA) and glutathione (GSH) were analyzed using high performance liquid chromatography. Tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 were assessed using enzyme-linked immunosorbent assay (ELISA). I-R caused tubular dilatation and brush border loss. LA decreased both renal dysfunction and abnormal levels of MDA and GSH during I-R. Moreover, LA decreased significantly both MMP-2 and MMP-9 expressions and activations during I-R. TIMP-1 and TIMP-2 levels were increased significantly by LA administration. LA modulated increased MMP-2 and MMP-9 activities and decreased TIMP-1 and TIMP-2 levels during renal I-R.

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Section: Discussionmentioning

confidence: 98%

The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model

Cavdar¹,

Özbal²,

Celik³

et al. 2013

Biotechnic & Histochemistry

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“…In the previous studies on the role of PPAR in diabetic kidney disease, it was found that the PPAR agonist could modulate systemic metabolism in a number of ways, including improvement of glycaemic control, insulin sensitivity and dyslipidaemia, and these modulatory effects might influence the outcome of the disease [31][32][33][34]. Later on, Zou et al [21] and Reel et al [35] concluded that pioglitazone was capable of protecting the kidney from renal injury by enhancing the antioxidative and anti-inflammatory capacity of the kidney. Furthermore, it was reported that pioglitazone significantly increased the expression of VEGF and accelerated the angiogenesis process following kidney injuries [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Ameliorates Chronic Kidney Disease by Enhancing Antioxidative Capacity and Attenuating Angiogenesis in the Kidney of a 5/6 Nephrectomized Rat Model

Sun

Yuan

et al. 2016

Cell Physiol Biochem

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Background/Aims: Pioglitazone is a type of peroxisome proliferator-activated receptor γ agonist and is capable of alleviating renal ischemia-reperfusion injury. Methods: A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs. Results: Subtotal nephrectomy caused severe damages to rat renal tissues, and administration of pioglitazone dramatically restored the structure and function of the kidney, which was evidenced by Periodic acid- Schiff staining and the reduced levels of urinary proteins, blood urea nitrogen, and creatinine. Furthermore, pioglitazone decreased the level of malondialdehyde and increased the level of superoxide dismutase in the injured renal tissues, suggesting that the antioxidative capacity in the injured kidney was augmented by pioglitazone. Additionally, pioglitazone inhibited HIF-1α-dependent angiogenesis by down-regulating the expression of a panel of angiogenic factors. Conclusion: The current study demonstrates that pioglitazone benefits renal failure through activation of the antioxidative system and inhibition of angiogenesis in the injured kidney. Our study provides preliminary evidences for the potential application of this agent in the treatment of CKDs.

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“…During cisplatin-induced AKI, down-regulation of PGC-1α mRNA in proximal tubule cells leads to acute tubular necrosis caused by inhibition of mitochondrial fatty acid oxidation 16 . Moreover, treatment with PPARγ agonists promotes PGC-1 α induction, and their effects ameliorate AKI 17 . However, the effect of PGC-1α in apoptotic cellular injury is controversial.…”

Section: Introductionmentioning

confidence: 99%

PGC-1α attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38 in HK-2 Cells

Choi

Kim

Park

et al. 2017

Sci Rep

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Ischemia/reperfusion injury triggers acute kidney injury (AKI) by aggravating oxidative stress mediated mitochondria dysfunction. The peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is a master player that regulates mitochondrial biogenesis and the antioxidant response. We postulated that PGC-1α functions as cytoprotective effector in renal cells and that its regulation mechanism is coordinated by nuclear factor erythroid 2-related factor 2 (Nrf-2). In this study, to understand the effect and molecular mechanisms of PGC-1α, we developed an empty vector or PGC-1α-overexpressing stable cell lines in HK-2 cells (Mock or PGC-1α stable cells). PGC-1α overexpression increased the viability of cells affected by H2O2 mediated injury, protected against H2O2-mediated apoptotic events and inhibited reactive oxygen species accumulation in the cytosol and mitochondria as compared to that in Mock cells. The cytoprotective effect of PGC-1α was related to Nrf-2 upregulation, which was counteracted by Nrf-2-specific knockdown. Using inhibitor of p38, we found that regulation of the p38/glycogen synthase kinase 3β (GSK3β)/Nrf-2 axis was involved in the protective effects of PGC-1α. Taken together, we suggest that PGC-1α protects human renal tubule cells from H2O2-mediated apoptotic injury by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38.

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The effects of PPAR-γ agonist pioglitazone on renal ischemia/reperfusion injury in rats

Cited by 56 publications

References 47 publications

The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model

The effects of alpha-lipoic acid on MMP-2 and MMP-9 activities in a rat renal ischemia and re-perfusion model

Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Ameliorates Chronic Kidney Disease by Enhancing Antioxidative Capacity and Attenuating Angiogenesis in the Kidney of a 5/6 Nephrectomized Rat Model

PGC-1α attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38 in HK-2 Cells

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