Role of PPAR-γ on the pathogenesis and vascular changes in glycerol-induced acute renal failure

Newaz, Mohammad; Yousefipour, Zivar; Oyekan, Adebayo

doi:10.1016/j.phrs.2006.03.023

Cited by 19 publications

(27 citation statements)

References 39 publications

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“…These observations indicate that a role exists for PPAR␥ in the regulation of renal vascular reactivity and thus renal function. In agreement with this, DNA microarray studies and our recent studies showed a down-regulation of PPAR␥ gene in the kidney from ARF rats induced by glycerol (Yoshida et al, 2002;Newaz et al, 2006). Based on these observations, we hypothesize that reduced PPAR␥ is involved in the pathogenesis of glycerolinduced ARF.…”

supporting

confidence: 88%

“…Previously, we have shown increased renal vascular reactivity in isolated perfused kidney from glycerol-induced ARF rats and its amelioration by CG (Newaz et al, 2006). Renal production and activity of AII and TxA 2 are critical in regulating vascular tone, and the response to these agonists is more contributory to the process of overall renal function or in developing ARF when they acted on resistance vessels rather than the capacitance vessels.…”

Section: Discussionmentioning

confidence: 95%

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Ciglitazone, a Peroxisome Proliferator-Activated Receptor γ Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A₂ in Glycerol-Induced Acute Renal Failure

Yousefipour

Hercule

Truong³

et al. 2007

J Pharmacol Exp Ther

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Peroxisome proliferator-activated receptor ␥ (PPAR␥), a nuclear transcription factor, modulates vascular responses to angiotensin II (AII) or thromboxane A 2 (TxA 2 ) via regulation of their gene/receptor. Increased vasoconstriction and deteriorating renal function in glycerol-induced acute renal failure (ARF) may be attributed to down-regulation of PPAR␥. In this study, we investigated the effect of ciglitazone (CG), a PPAR␥ inducer, on AII and TxA 2 production and activity in glycerol-induced ARF. Vascular responses to AII or 9,11-dideoxy-11␣,9␣-epoxymethano prostaglandin F 2␣ (U46619), a TxA 2 mimetic, were determined in preglomerular vessels following induction of ARF with glycerol. Renal damage and function were assessed in CG-treated (9 nmol/kg for 21 days) rats. PPAR␥ protein expression and activity, which were significantly lower in ARF rats, were enhanced by CG (26 and 30%). CG also increased PPAR␥ mRNA by 67 Ϯ 6%, which was reduced in ARF. In ARF, there was significant tubular necrosis and apoptosis, a 5-fold increase in proteinuria and a 2-fold enhancement in vasoconstriction to AII and U46619. CG reduced proteinuria (49 Ϯ 3%), enhanced Na ϩ (124 Ϯ 35%) and creatinine excretion (92 Ϯ 25%), markedly diminished tubular necrosis, and reduced ARFinduced increase in AII (40 Ϯ 3%) and TxA 2 (39 Ϯ 2%) production, the attending increase in vasoconstriction to AII (36 Ϯ 2%) and U46619 (50 Ϯ 11%), and the increase in angiotensin receptor-1 (AT 1 ) (23 Ϯ 3%) or thromboxane prostaglandin (TP) receptor (13 Ϯ 1%). CG reduced free radical generation by 55 Ϯ 14% while elevating nitrite excretion (65 Ϯ 13%). Our results suggest that enhanced activity of AII and TxA 2 , increased AT 1 or TP receptor expression, and renal injury in glycerol-induced ARF are consequent to down-regulation of PPAR␥ gene. CG ameliorated glycerol-induced effects through maintaining PPAR␥ gene.

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supporting

confidence: 88%

Section: Discussionmentioning

confidence: 95%

Ciglitazone, a Peroxisome Proliferator-Activated Receptor γ Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A₂ in Glycerol-Induced Acute Renal Failure

Yousefipour

Hercule

Truong³

et al. 2007

J Pharmacol Exp Ther

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“…Induction of PRAR␥ has been shown to reverse the renal damage and restore glomerular function (21). Moreover, diabetes is associated with impaired renal function (26).…”

Section: Resultsmentioning

confidence: 99%

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Sen¹,

Rodríguez²,

Tyagi³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Sen U, Rodriguez WE, Tyagi N, Kumar M, Kundu S, Tyagi SC. Ciglitazone, a PPAR␥ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance. Am J Physiol Endocrinol Metab 295: E1205-E1212, 2008. First published September 9, 2008 doi:10.1152/ajpendo.90534.2008.-Diabetes and hyperhomocysteinemia (HHcy) are two independent risk factors for glomeruloslerosis and renal insufficiency. Although PPAR␥ agonists such as ciglitazone (CZ) are known to modulate diabetic nephropathy, the role of CZ in diabetes-associated HHcy and renopathy is incompletely defined. We tested the hypothesis that induction of PPAR␥ by CZ decreases tissue Hcy level; this provides a protective role against diabetic nephropathy. C57BL/6J mice were administered alloxan to create diabetes. Mice were grouped to 0, 1, 10, 12, and 16 wk of treatment; only 12-and 16-wk animals received CZ in drinking water after a 10-wk alloxan treatment. In diabetes, PPAR␥ cDNA, mRNA, and protein expression were repressed, whereas an increase in plasma and glomerular Hcy levels was observed. CZ normalized PPAR␥ mRNA and protein expression and glomerular level of Hcy, whereas plasma level of Hcy remained unchanged. GFR was dramatically increased at 1-wk diabetic induction, followed by hypofiltration at 10 wk, and was normalized by CZ treatment. This result corroborated with glomerular and preglomerular arteriole histology. A steady-state increase of RVR in diabetic mice became normal with CZ treatment. CZ ameliorated decrease bioavailability of NO in the diabetic animal. Glomerular MMP-2 and MMP-9 activities as well as TIMP-1 expression were increased robustly in diabetic mice and normalized with CZ treatment. Interestingly, TIMP-4 expression was opposite to that of TIMP-1 in diabetic and CZ-treated groups. These results suggested that diabetic nephropathy exacerbated glomerular tissue level of Hcy, and this caused further deterioration of glomerulus. CZ, however, protected diabetic nephropathy in part by activating PPAR␥ and clearing glomerular tissue Hcy.peroxisome proliferator-activated receptor-␥; matrix metalloproteinase; tissue inhibitor of metalloproteinases; glomerulosclerosis PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-␥ (PPAR␥) is a member of nuclear hormone receptor superfamily of ligandactivated transcription factors. It plays important roles in maintaining glucose and lipid homeostasis (39). The PPAR␥ agonists, such as ciglitazone (CZ), are agents that improve glycemic control by increasing insulin sensitivity (5). These agonists also mediate direct antiatherogenic effects in the diabetic vasculature that are independent of their metabolic actions (4). In the pathogenesis of diabetic vasculopathies, such as in glomerulosclerosis, downregulated PPAR␥ expression is associated with matrix accumulation and glomerulonephritis (23,30,39). Several studies have shown the efficacy of PPAR␥ agonists to ameliorate the progression of glomerulosclerosis (15) and have suggested that PPAR␥ ligands have a direct beneficial renal effect. However, the role...

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“…45) Nox-4 was originally described as a kidney-specific Nox isoform, which has been defined on the basis of its homology with the gp91 phox catalytic subunit of phagocyte NAD(P)H oxidase. Newaz et al 46) demonstrated that increased free radical generation in this model of ARF was associated with an increased NAD(P)H oxidase activity and increased expression of the NAD(P)H oxidase components p47 phox and p22 phox . Therefore, in the present study, the effect of GS under ARF on the expression of Nox-4 and p22 phox was observed.…”

Section: Discussionmentioning

confidence: 77%

Glycerol-Induced Renal Damage Improved by 7-O-Galloyl-D-sedoheptulose Treatment through Attenuating Oxidative Stress

Park

Tanaka

Cho

et al. 2012

Biological & Pharmaceutical Bulletin

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The protective effect of 7-O-galloyl-D-sedoheptulose (GS), isolated from Corni Fructus as an active component, against acute renal failure (ARF) induced by glycerol was investigated. The administration of GS led to a decline in the levels of blood urea nitrogen and creatinine; on the other hand, it did not have a significant effect on creatinine clearance. Furthermore, GS also significantly decreased the urine volume and fractional excretion of sodium, but it increased the urine osmolarity, suggesting the protective role of GS against renal dysfunction. Oxidative stress under ARF was attenuated by GS through the inhibition of lipid peroxidation, scavenging of reactive oxygen species (ROS), and elevation of the antioxidative status. Renal oxidative stress is related to the overproduction of ROS by nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase; therefore, in the present study, the protein expression of p22 phox and NAD(P)H oxidase-4 (Nox-4) was investigated. GS down-regulated the protein expression of p22 phox ; on the other hand, it did not significantly affect the expression of Nox-4. This indicates that GS inhibits the production of superoxide by regulating a component of NAD(P)H oxidase, p22 phox . Furthermore, GS down-regulated the expressions of nuclear factor-κB (NF-κΒ) and inducible nitric oxide (NO) synthase (iNOS), suggesting that GS protects against NO-induced inflammatory pathological conditions under ARF through the regulation of NF-κB and iNOS expressions. The present study indicates that GS exerts a protective effect against ARF through the recovery of renal dysfunction and attenuation of renal oxidative stress by regulating related protein expression.Key words 7-O-galloyl-D-sedoheptulose; Corni Fructus; acute renal failure; glycerol; oxidative stress Acute renal failure (ARF) is a syndrome characterized by an acute loss of renal function. Despite the reversibility of this loss in most patients who survive, mortality from ARF remains high (over 50%).1) Therefore, the search for effective therapy to accelerate recovery and attempts to prevent ARF have attracted much attention. The most commonly used model for studying ARF is a rat receiving a single intramuscular injection of glycerol, which induces rhabdomyolysis. 2,3)

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Role of PPAR-γ on the pathogenesis and vascular changes in glycerol-induced acute renal failure

Cited by 19 publications

References 39 publications

Ciglitazone, a Peroxisome Proliferator-Activated Receptor γ Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A₂ in Glycerol-Induced Acute Renal Failure

Ciglitazone, a Peroxisome Proliferator-Activated Receptor γ Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A₂ in Glycerol-Induced Acute Renal Failure

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Glycerol-Induced Renal Damage Improved by 7-O-Galloyl-D-sedoheptulose Treatment through Attenuating Oxidative Stress

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Role of PPAR-γ on the pathogenesis and vascular changes in glycerol-induced acute renal failure

Cited by 19 publications

References 39 publications

Ciglitazone, a Peroxisome Proliferator-Activated Receptor γ Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A2 in Glycerol-Induced Acute Renal Failure

Ciglitazone, a Peroxisome Proliferator-Activated Receptor γ Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A2 in Glycerol-Induced Acute Renal Failure

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Glycerol-Induced Renal Damage Improved by 7-O-Galloyl-D-sedoheptulose Treatment through Attenuating Oxidative Stress

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Ciglitazone, a Peroxisome Proliferator-Activated Receptor γ Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A₂ in Glycerol-Induced Acute Renal Failure

Ciglitazone, a Peroxisome Proliferator-Activated Receptor γ Inducer, Ameliorates Renal Preglomerular Production and Activity of Angiotensin II and Thromboxane A₂ in Glycerol-Induced Acute Renal Failure