Role of Angiotensin II on Dihydrofolate Reductase, GTP-Cyclohydrolase 1 and Nitric Oxide Synthase Expressions in Renal Ischemia-Reperfusion

Seujange, Yuyen; Eiam-Ong, Somchit; Tirawatnapong, Thaweesak; Eiam‐Ong, Somchai

doi:10.1159/000126927

Cited by 15 publications

(15 citation statements)

References 59 publications

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“…Activation of the renin-angiotensin pathway with increased production of Ang-II plays an important role in the pathogenesis of renal I/R injury. 6,7 Ang-II is a well-known oxidative stress inducer, and ROS are involved in many of the Ang-II signaling pathways. Ang-II, through the AT1 receptor, stimulates the NADPH oxidase enzyme with increased generation of superoxide anion, hydrogen peroxide, and hydroxyl radicals.…”

Section: Discussionmentioning

confidence: 99%

“…Ang-II, by activating the Ang-II type 1 (AT1) receptor, increases generation of reactive oxygen species (ROS) and proinflammatory mediators, particularly tumor necrosis factor-a (TNF-a), which are greatly responsible for renal damage induced by I/R. 6,7 Also, I/R impairs renal homocysteine metabolism leading to homocysteine accumulation in the kidney, which contributes to I/Rinduced oxidative stress with renal cell death. 8 Peroxisome proliferator-activated receptor (PPAR)-a is one of the three subtypes of the nuclear receptor PPAR family, which can be activated by natural ligands, such as polyunsaturated fatty acids, and synthetic ligands.…”

Section: Introductionmentioning

confidence: 99%

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Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

et al. 2010

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It was demonstrated that fenofibrate and telmisartan exerted renoprotective effects in ischemia/reperfusion (I/R) injury. Because the combination of fenofibrate and telmisartan synergistically enhanced peroxisome proliferator-activated receptor (PPAR) activation, we hypothesized that the combination of both drugs may exert prolonged beneficial effects in renal I/R injury than fenofibrate alone. Forty-eight male Wistar albino rats were divided into eight groups. Hyperlipidemia was induced by cholesterol feeding for 4 weeks. At the end of the fourth week, renal I/R injury was performed by occlusion of both renal vascular pedicles for 60 minutes, followed by 24 hours of reperfusion. In the treatment group, fenofibrate alone and in combination with telmisartan was administered 2 weeks prior to renal ischemia. At the end of the experiment, blood and kidneys were isolated for biochemical and histological analysis. I/R in hyperlipidemic rat shows significantly increased lipid peroxidation, nitric oxide, and myeloperoxidase activity, and depletion of antioxidant enzyme compared with control rats, and that was significantly restored after fenofibrate and telmisartan treatment. Also, significant increases in serum homocysteine level were detected following I/R. Fenofibrate treatment further elevated homocysteine level, which was reduced by telmisartan in combination with fenofibrate. The most significant histological damage was found in the hyperlipidemic rat subjected to renal I/R, which was reduced significantly with combination therapy. The results of this study concluded that fenofibrate alone and in combination with telmisartan significantly ameliorated renal I/R injury. The additive beneficial effect of telmisartan is predicted to reduce homocysteine-induced oxidative stress through reduced nitric oxide production during I/R.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

et al. 2010

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“…All animal protocols were approved by the Ethics Committee of Research, Chulalongkorn University. The serum creatinine should be <1 mg/dl [12]. The rats were divided into three groups (n = 8/group): (1) sham (normal saline solution; NSS: 0.5 ml/kg BW by intraperitoneal injection, i.p.…”

Section: Methodsmentioning

confidence: 99%

“…The measurement of protein abundance was performed as previously described [12]. The proteins were resolved on 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) for pEGFR or pERK1/2 and blotted onto nitrocellulose membrane (Bio-Rad, Hercules, Calif., USA).…”

Section: Methodsmentioning

confidence: 99%

Nongenomic Effects of Aldosterone on Renal Protein Expressions of pEGFR and pERK1/2 in Rat Kidney

Sinphitukkul

Eiam-Ong²,

Manotham³

et al. 2010

Am J Nephrol

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Background: In vitro studies have demonstrated that aldosterone elicits nongenomic actions by enhancing protein expressions of phosphorylated epidermal growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2). There are no available in vivo investigations regarding this action of aldosterone on renal pEGFR-pERK1/2 protein expressions. Methods: Male Wistar rats received normal saline solution, low-dose (LA: 150 µg/kg BW) or high-dose aldosterone (HA: 500 µg/kg BW) by intraperitoneal injection. After 30 min, protein abundances and localizations of renal pEGFR and pERK1/2 were determined by Western blot and immunohistochemistry. Results: Plasma aldosterone levels were increased in LA and HA groups (p < 0.001). Aldosterone enhanced renal pEGFR and pERK1/2 protein abundances (p < 0.001). HA showed a greater stimulation on pEGFR immunoreactivity than LA in the glomerulus, vasa recta, and thin limb of Henle’s loop in the inner medulla area. LA provided more reactivity of pERK1/2 in the thick ascending limb of Henle’s loop, outer medullary collecting duct, and proximal straight tubule, whereas HA illustrated more pERK1/2 activation in the glomerulus, peritubular capillary, and inner medulla region. Conclusion: This is the first in vivo study which demonstrates that aldosterone, via the nongenomic pathway, could elevate pEGFR and pERK1/2 protein abundances and expressions in the rat kidney. These results indicate that aldosterone induces phosphorylation of EGFR upstream of ERK1/2.

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“…21,22 Although some experiments have suggested a protective effect of angiotensin-converting enzyme inhibition or ARB therapy early during ischemic-reperfusion kidney injury, outcomes with these agents have not been uniformly favorable. [23][24][25][26] One concern with these treatments is the risk of hemodynamic insult related to an acute lowering of glomerular filtration pressure. These studies, therefore, parse the mechanisms underpinning the mixed effects of global RAS inhibition during cisplatin-induced AKI by defining the distinct roles of AT 1 receptors on T cells and kidney epithelial cells in this setting and documenting the critical contribution of TNF in the distal nephron to cisplatin nephrotoxicity.…”

mentioning

confidence: 99%

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI

Zhang¹,

Rudemiller²,

Patel³

et al. 2016

JASN

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Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT 1 ) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-a is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-a is suppressed or enhanced by AT 1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT 1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-a levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT 1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-a production induced by cisplatin. Finally, disrupting TNF-a production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-a levels induced by cisplatin. These results illustrate discrepant tissue-specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT 1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.

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Role of Angiotensin II on Dihydrofolate Reductase, GTP-Cyclohydrolase 1 and Nitric Oxide Synthase Expressions in Renal Ischemia-Reperfusion

Cited by 15 publications

References 59 publications

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

Role of fenofibrate alone and in combination with telmisartan on renal ischemia/reperfusion injury

Nongenomic Effects of Aldosterone on Renal Protein Expressions of pEGFR and pERK1/2 in Rat Kidney

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI

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