Amelioration of Renal Ischemia-Reperfusion Injury With a Novel Protective Cocktail

Dorai, Thambi; Fishman, Andrew I.; Ding, Cheng; Batinić‐Haberle, Ines; Goldfarb, David S.; Grasso, Michael

doi:10.1016/j.juro.2011.08.010

Cited by 43 publications

(52 citation statements)

References 23 publications

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“…It contributes to the development of acute renal failure (ARF), which is associated with high mortality and morbidity in patients with transplanted kidney. 3 A substantial amount of study to date has focused on the mechanism of oxidative stress and cell apoptosis in renal I/R injury, so many therapeutic method aimed at oxidative stress and apoptosis has been reported to protection renal injury. [26][27][28] Nesfatin-1, an 82-amino-acid peptide, has been reported to possess antioxidative, antiinflammation and anti-apoptotic properties.…”

Section: Discussionmentioning

confidence: 99%

“…It contributes to the development of acute renal failure (ARF), which is associated with high mortality and morbidity in patients with transplanted kidney. 3 The mechanisms underlying IR injury are complex and incompletely understood, but oxidative stress, necrosis, cell apoptosis, ATP depletion and calcium dyshomeostasis undoubtedly contribute to the mechanisms of renal ischemia-reperfusion injury. [4][5][6][7][8] When renal I/R injury occurs, the increased generation of reactive oxygen species (ROS) in the reperfusion phase leads to lipid peroxidation, DNA mutation, as well as initiation of apoptotic and necrotic cascades, and ultimately leading to cell death.…”

Section: Introductionmentioning

confidence: 99%

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The protective effect of nesfatin-1 against renal ischemia–reperfusion injury in rats

Jiang

Wang

et al. 2015

Renal Failure

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(2015) The protective effect of nesfatin-1 against renal ischemia-reperfusion injury in rats, Renal Failure, 37:5,[882][883][884][885][886][887][888][889] LABORATORY STUDYThe protective effect of nesfatin-1 against renal ischemia-reperfusion injury in rats Guanjun Jiang, Min Wang, Lei Wang, Hui Chen, Zhiyuan Chen, Jia Guo, Xiaodong Weng, and Xiuheng Liu Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, PR China Abstract Introduction: The pathogenetic mechanisms underlying ischemia-reperfusion (I/R) injury involve oxidative stress, inflammation and apoptosis. Nesfatin-1, a novel peptide, has been reported to possess antioxidant, anti-inflammatory and anti-apoptic properties. The study was to examine the potential protective effects of nesfatin-1 on renal I/R injury. Materials and methods: I/R model was induced by placing a clamp across left renal artery for 45 min followed by 24 h reperfusion, along with a contralateral nephrectom. Twenty-four rats divided into three groups: sham-operated group, vehicle-treated I/R and nesfatin-1-treated I/R. Nesfatin-1 was intraperitoneally injected 30 min before renal ischemia. We harvested serum and kidneys at 24 h after reperfusion. Renal function and histological changes were assessed. Marker of oxidative stress and cells in kidney were also evaluated. Results: The animals with nesfatin-1 significantly improved renal functional and histologic lesions induced by I/R injury. The malondialdehyde (MDA) level decreased, whereas superoxide dismutase (SOD) and catalase (CAT) activities were significantly increased. Moreover, nesfatin-1-treated rats had a markedly decrease in apoptotic tubular cells, as well as a decrease in caspase-3 activity and an increase in the bcl-2/Bax ratio. Conclusions: This is the first evidence that nesfatin-1 treatment ameliorates acute renal I/R injury by suppressing oxidative stress and cell apoptosis. Therefore, it is promising as a potential therapeutic agent for renal IR injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The protective effect of nesfatin-1 against renal ischemia–reperfusion injury in rats

Jiang

Wang

et al. 2015

Renal Failure

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“…Dorai's group substantiated the fact that MnP can cause adaptive response via a mild pro-oxidative stress (75). MnTnHex-2-PyP 5 + was administered as a part of GMP treatment that contained specific renoprotective growth factors and mitochondria-protecting amino acids.…”

Section: ) (D)mentioning

confidence: 99%

SOD Therapeutics: Latest Insights into Their Structure-Activity Relationships and Impact on the Cellular Redox-Based Signaling Pathways

Batinić‐Haberle

Tovmasyan

Roberts

et al. 2014

Antioxidants & Redox Signaling

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206

458

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Significance: Superoxide dismutase (SOD) enzymes are indispensable and ubiquitous antioxidant defenses maintaining the steady-state levels of O 2 $ -; no wonder, thus, that their mimics are remarkably efficacious in essentially any animal model of oxidative stress injuries thus far explored. Recent Advances: Structure-activity relationship (half-wave reduction potential [E 1/2 ] versus log k cat ), originally reported for Mn porphyrins (MnPs), is valid for any other class of SOD mimics, as it is dominated by the superoxide reduction and oxidation potential. The biocompatible E 1/2 of *+300 mV versus normal hydrogen electrode (NHE) allows powerful SOD mimics as mild oxidants and antioxidants (alike O 2 $ -) to readily traffic electrons among reactive species and signaling proteins, serving as fine mediators of redox-based signaling pathways. Based on similar thermodynamics, both SOD enzymes and their mimics undergo similar reactions, however, due to vastly different sterics, with different rate constants. Critical Issues: Although log k cat (O 2 $ -) is a good measure of therapeutic potential of SOD mimics, discussions of their in vivo mechanisms of actions remain mostly of speculative character. Most recently, the therapeutic and mechanistic relevance of oxidation of ascorbate and glutathionylation and oxidation of protein thiols by MnP-based SOD mimics and subsequent inactivation of nuclear factor jB has been substantiated in rescuing normal and killing cancer cells. Interaction of MnPs with thiols seems to be, at least in part, involved in up-regulation of endogenous antioxidative defenses, leading to the healing of diseased cells. Future Directions: Mechanistic explorations of single and combined therapeutic strategies, along with studies of bioavailability and translational aspects, will comprise future work in optimizing redox-active drugs. Antioxid. Redox Signal. 20, 2372Signal. 20, -2415

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“…Galectin-3 is one of a family of lectins (otherwise known as MAC-2 Ag) whose main target is myofibroblasts via intracellular signaling, which translate the transforming growth factor-β signal for increase cell cycle (cyclin D 1 ) enabling a marked production of procollagen I which is ultimately cross-linked into mature collagen [34]. Translational studies have demonstrated that a similar process of organ fibrosis can be turned on in the kidney resulting in progressive CKD in the setting of HF, warm renal ischemia-reperfusion injury, and renal transplantation degeneration [35,36]. Thus, in CRS type 2, HF incites a sequence of processes involving the endothelium, glycocalyx, tubules, nephron units, and fibroblasts in the skeleton of the kidney that result in progressive loss of functioning nephrons and replacement of tissue with fibrosis (fig.…”

Section: Resultsmentioning

confidence: 99%

Pathophysiology of the Cardiorenal Syndromes: Executive Summary from the Eleventh Consensus Conference of the Acute Dialysis Quality Initiative (ADQI)

et al. 2014

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Cardiorenal syndromes (CRS) have been recently classified into five distinct entities, each with different major pathophysiologic mechanisms. CRS type 1 most commonly occurs in the setting of acutely decompensated heart failure where approximately 25% of patients develop a rise in serum creatinine and a reduction of urine output after the first several doses of intravenous diuretics. Altered cardiac and renal hemodynamics are believed to be the most important determinants of CRS type 1. CRS type 2 is the hastened progression of chronic kidney disease (CKD) in the setting of chronic heart failure. Accelerated renal cell apoptosis and replacement fibrosis is considered to be the dominant mechanism. CRS type 3 is acutely decompensated heart failure after acute kidney injury from inflammatory, toxic, or ischemic insults. This syndrome is precipitated by salt and water overload, acute uremic myocyte dysfunction, and neurohormonal dysregulation. CRS type 4 is manifested by the acceleration of the progression of chronic heart failure in the setting of CKD. Cardiac myocyte dysfunction and fibrosis, so-called ‘CKD cardiomyopathy', is believed to be the predominant pathophysiologic mechanism. Type 5 CRS is simultaneous acute cardiac and renal injury in the setting of an overwhelming systemic insult such as sepsis. In this scenario, the predominant pathophysiological disturbance is microcirculatory dysfunction as a result of acutely abnormal immune cell signaling, catecholamine cellular toxicity, and enzymatic activation which result in simultaneous organ injury often extending beyond both the heart and the kidneys. This paper will summarize these and other key findings from an international consensus conference on the spectrum of pathophysiologic mechanisms at work in the CRS.

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Amelioration of Renal Ischemia-Reperfusion Injury With a Novel Protective Cocktail

Abstract: According to histopathological and several molecular measures our unique renoprotective cocktail mitigated ischemia-reperfusion injury.

Cited by 43 publications

References 23 publications

The protective effect of nesfatin-1 against renal ischemia–reperfusion injury in rats

The protective effect of nesfatin-1 against renal ischemia–reperfusion injury in rats

SOD Therapeutics: Latest Insights into Their Structure-Activity Relationships and Impact on the Cellular Redox-Based Signaling Pathways

Pathophysiology of the Cardiorenal Syndromes: Executive Summary from the Eleventh Consensus Conference of the Acute Dialysis Quality Initiative (ADQI)

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