Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the causative role of oxidative stress in renal ischemia-reperfusion (I-R) injury effects of preservation solutions on reactive oxygen species (ROS) release have not been sufficiently evaluated. We compared the effects of most common solutions in kidney transplantation, University of Wisconsin (UW) and Histidine-Tryptophan-Ketoglutarate (HTK). ROS formation in isolated perfused rat kidney was detected by electron spin resonance spectroscopy using spin label 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Donor kidneys from Lewis rats were pretreated with saline (controls), in therapeutic groups, kidneys underwent 18 h of cold storage (CS) preserved by HTK or UW solution. Experimental protocol included a stabilization period followed by additional I-R. Kidneys preserved by HTK produced highest ROS values in the control period after CS, whereas levels in UW and control group did not vary significantly. A peak release induced by additional I-R was also significantly highest in HTK kidneys, and UW did not differ from controls. During reperfusion, levels in HTK exceeded control and UW values. Renal vascular resistance, caspase-3-activity, and tissue hydration were enhanced in HTK compared with UW group, whereas ATP concentration was less reduced in UW-preserved tissue. These data show the greater antioxidative potential of UW solution, which also attenuated organ impairment after CS in the early reperfusion period.
 ...
PMID:Evaluation of preservation solutions by ESR-spectroscopy: superior effects of University of Wisconsin over Histidine-Tryptophan-Ketoglutarate in reducing renal reactive oxygen species. 1731 Oct 72

Renal ischemia/reperfusion (I/R) injury often occurs as a result of vascular surgery, organ procurement, or transplantation. We previously showed that renal I/R results in ATP depletion, oxidant production, and manganese superoxide dismutase (MnSOD) inactivation. There have been several reports that overexpression of MnSOD protects tissues/organs from I/R-related damage, thus a loss of MnSOD activity during I/R likely contributes to tissue injury. The present study examined the therapeutic benefit of a catalytic antioxidant, Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), using the rat renal I/R model. This was the first study to examine the effects of MnTnHex-2-PyP(5+) in an animal model of oxidative stress injury. Our results showed that porphyrin pretreatment of rats for 24 h protected against ATP depletion, MnSOD inactivation, nitrotyrosine formation, and renal dysfunction. The dose (50 microg/kg) used in this study is lower than doses of various types of antioxidants commonly used in animal models of oxidative stress injuries. In addition, using novel proteomic techniques, we identified the ATP synthase-beta subunit as a key protein induced by MnTnHex-2-PyP(5+) treatment alone and complex V (ATP synthase) as a target of injury during renal I/R. These results showed that MnTnHex-2-PyP(5+) protected against renal I/R injury via induction of key mitochondrial proteins that may be capable of blunting oxidative injury.
 ...
PMID:Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion. 1744 4

Bid, a BH3-only member of the Bcl-2 family proteins, is most abundantly expressed in the kidneys. Recent research has shown Bid activation in renal tubular cells in vitro following ATP-depletion and hypoxic injury, and also in vivo during renal ischemia-reperfusion in rats and mice. Importantly, Bid-deficient mice are resistant to ischemic kidney injury. Targeting Bid may therefore offer a new strategy for the treatment of acute renal failure associated with ischemia-reperfusion.
 ...
PMID:Regulation and pathological role of bid in ischemic acute kidney injury. 1806 37

Renal ischemia was induced in the rat by constriction of the renal artery for 45 min, and the ability of the ATP-sensitive K(+) (K(ATP)) channel opener diazoxide (DZ) to ameliorate renal ischemia-reperfusion (I/R) injury was evaluated. In this model, blood urea nitrogen and creatinine were elevated 2 days after I/R injury but returned closer to normal levels by 7 days after reperfusion. Histological staining for reactive oxygen species (ROS) was clearly positive and oxidized DNA, detected by the presence of the stable adduct 8-hydroxy-2'-deoxyguanosine, was clearly present in the cytoplasm of tubular cells after 1 h of reperfusion and declined 7 days after reperfusion. This finding was confirmed by ELISA, which detected 8-hydroxy-2'-deoxyguanosine in the mitochondrial fraction of kidney homogenates. Despite evidence of improved function measured by blood urea nitrogen and creatinine 7 days after reperfusion, the early changes in tubules were alarming. Mitochondrial DNA showed the common deletion, and the number of TdT-mediated dUTP nick-end label-positive tubular cells increased. Activation of caspase-3 continued, and abnormal levels of ROS were found in the mitochondrial fraction of cellular homogenates. Treatment with DZ before ischemia reduced or prevented the acute and subacute deleterious effects associated with renal I/R injury. We conclude that excess production of ROS by mitochondria on reperfusion is a major upstream event in renal reperfusion injury and that DZ functioned by preventing ROS accumulation in the mitochondria after I/R injury, thereby reducing oxidative stress as measured by the presence of oxidized mitochondrial DNA and features of apoptosis.
 ...
PMID:Amelioration of oxidative mitochondrial DNA damage and deletion after renal ischemic injury by the KATP channel opener diazoxide. 1816 Jun 22

The cellular pathophysiology of renal ischemia-reperfusion injury was investigated in primary cell cultures from rabbit medullary thick ascending limb (MTAL). Metabolic inhibition (MI) was achieved with cyanide and 2-deoxyglucose. Sixty minutes of MI caused a profound but reversible decrease in intracellular concentration of ATP ([ATP]i). Intracellular pH (pHi) first decreased after initiation of MI, followed by a transient alkalinization. When [ATP]i reached its lowest value (<1% of control), the cells slowly acidified to reach a stable pHi of 6.92 after 50 min of MI. In the presence of EIPA (10 micromol/L), the pattern of changes in pHi was unchanged and acidification was not increased, indicating that the Na+/H+ exchangers were inactive during ATP depletion. When inorganic phosphate (P(i)) or Na+ was omitted from the apical solutions during MI, the transient alkalinization was no longer observed and the cytosol slowly acidified. Experiments on Na+-dependent alkalinizations revealed the presence of a Na-P(i) cotransporter in the apical cell membrane. With indirect immunofluorescence, the Na-P(i) cotransporter expressed in these primary cell cultures could be identified as Na-P(i) type I. Although the exact physiological role of Na-P(i) type I still is unresolved, these experiments demonstrate that apical Na-P(i) type I activity is increased at the onset of ATP depletion in MTAL cells.
 ...
PMID:Na-P(i) cotransporter type I activity causes a transient intracellular alkalinization during ATP depletion in rabbit medullary thick ascending limb cells. 1841 45

Acute kidney injury (AKI) is a serious condition that affects many ICU patients. The most common causes of AKI in ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite of our increasing ability to support vital organs. This is partly due to our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. However, new concepts are emerging to explain the pathogenesis of septic AKI, which challenge previously held dogma. Throughout the past half century, septic AKI has essentially been considered secondary to kidney ischemia. However, recent models of experimental sepsis have challenged this notion by demonstrating that, in experimental states, which simulate the hemodynamic picture most typically seen in man (e.g. hyperdynamic sepsis) renal blood flow, actually increases as renal vascular resistance decreases. These experimental observations provide proof of concept that septic AKI can occur in the setting of renal hyperemia and that ischemia is not necessary for loss of glomerular filtration rate (GFR) to occur. They also suggest that similar hemodynamic event may occur in man. In addition, preliminary studies in septic sheep show that, when ATP is measured using an implanted phosphorus coil and magnetic resonance technology, renal bioenergetics are preserved in the setting of advanced septic shock. While these findings need to be confirmed, they challenge established paradigms and offer a new conceptual framework of reference for further investigation and intervention in man.
 ...
PMID:Septic acute kidney injury: new concepts. 1880 75

Glomerular injury is often characterized by the effacement of podocytes, loss of slit diaphragms, and proteinuria. Renal ischemia or the loss of blood flow to the kidneys has been widely associated with tubular and endothelial injury but rarely has been shown to induce podocyte damage and disruption of the slit diaphragm. In this study, we have used an in vivo rat ischemic model to demonstrate that renal ischemia induces podocyte effacement with loss of slit diaphragm and proteinuria. Biochemical analysis of the ischemic glomerulus shows that ischemia induces rapid loss of interaction between slit diaphragm junctional proteins Neph1 and ZO-1. To further understand the effect of ischemia on molecular interactions between slit diaphragm proteins, a cell culture model was employed to study the binding between Neph1 and ZO-1. Under physiologic conditions, Neph1 co-localized with ZO-1 at cell-cell contacts in cultured human podocytes. Induction of injury by ATP depletion resulted in rapid loss of Neph1 and ZO-1 binding and redistribution of Neph1 and ZO-1 proteins from cell membrane to the cytoplasm. Recovery resulted in increased Neph1 tyrosine phosphorylation, restoring Neph1 and ZO-1 binding and their localization at the cell membrane. We further demonstrate that tyrosine phosphorylation of Neph1 mediated by Fyn results in significantly increased Neph1 and ZO-1 binding, suggesting a critical role for Neph1 tyrosine phosphorylation in reorganizing the Neph1-ZO-1 complex. This study documents that renal ischemia induces dynamic changes in the molecular interactions between slit diaphragm proteins, leading to podocyte damage and proteinuria.
 ...
PMID:Ischemic injury to kidney induces glomerular podocyte effacement and dissociation of slit diaphragm proteins Neph1 and ZO-1. 1892 1

ATP dependent K channels (K-ATP) take part in the Erythropoietin (EPO) induced cardioprotection but these channel activations have role in cytoprotective role of EPO in the renal ischemia reperfusion (IR) damage is still unknown. For this purpose rats were pretreated with EPO (500 IU/kg) and/or K-ATP channel blocker glibenclamide (40 mM/kg) i.p. before bilateral renal IR damage. Renal tissues were used for histological examination and measurement of caspase-3 and TNF-alpha levels. Renal functions were evaluated by glomerular filtration rate (GFR) fractional excretion of sodium (FENa) and potassium (FEK). Renal TNF-alpha and caspase-3 levels were decreased in both glibenclamide and EPO-treated IR rats compared to untreated rats. The protection afforded by the pretreatment with EPO alone was greater than that of administering glibenclamide alone. Application of glibenclamide at the same time partly abolished the cytoprotective effect of EPO treatment. K-ATP mediated cytoprotection is not the main mechanism of protective effect of EPO.
 ...
PMID:The effect of K-ATP channel blockage during erythropoietin treatment in renal ischemia-reperfusion injury. 1916 Jan 44

Prolonged ischemia amplified iscehemia/reperfusion (IR) induced renal apoptosis and autophagy. We hypothesize that ischemic conditioning (IC) by a briefly intermittent reperfusion during a prolonged ischemic phase may ameliorate IR induced renal dysfunction. We evaluated the antioxidant/oxidant mechanism, autophagy and apoptosis in the uninephrectomized Wistar rats subjected to sham control, 4 stages of 15-min IC (I15 x 4), 2 stages of 30-min IC (I30 x 2), and total 60-min ischema (I60) in the kidney followed by 4 or 24 hours of reperfusion. By use of ATP assay, monitoring O2-. amounts, autophagy and apoptosis analysis of rat kidneys, I60 followed by 4 hours of reperfusion decreased renal ATP and enhanced reactive oxygen species (ROS) level and proapoptotic and autophagic mechanisms, including enhanced Bax/Bcl-2 ratio, cytochrome C release, active caspase 3, poly-(ADP-ribose)-polymerase (PARP) degradation fragments, microtubule-associated protein light chain 3 (LC3) and Beclin-1 expression and subsequently tubular apoptosis and autophagy associated with elevated blood urea nitrogen and creatinine level. I30 x 2, not I15 x 4 decreased ROS production and cytochrome C release, increased Manganese superoxide dismutase (MnSOD), Copper-Zn superoxide dismutase (CuZnSOD) and catalase expression and provided a more efficient protection than I60 against IR induced tubular apoptosis and autophagy and blood urea nitrogen and creatinine level. We conclude that 60-min renal ischemia enhanced renal tubular oxidative stress, proapoptosis and autophagy in the rat kidneys. Two stages of 30-min ischemia with 3-min reperfusion significantly preserved renal ATP content, increased antioxidant defense mechanisms and decreased ischemia/reperfusion enhanced renal tubular oxidative stress, cytosolic cytochrome C release, proapoptosis and autophagy in rat kidneys.
 ...
PMID:Ischemic conditioning by short periods of reperfusion attenuates renal ischemia/reperfusion induced apoptosis and autophagy in the rat. 1927 87

The mechanism of mitochondrial damage, a key contributor to renal tubular cell death during acute kidney injury, remains largely unknown. Here, we have demonstrated a striking morphological change of mitochondria in experimental models of renal ischemia/reperfusion and cisplatin-induced nephrotoxicity. This change contributed to mitochondrial outer membrane permeabilization, release of apoptogenic factors, and consequent apoptosis. Following either ATP depletion or cisplatin treatment of rat renal tubular cells, mitochondrial fragmentation was observed prior to cytochrome c release and apoptosis. This mitochondrial fragmentation was inhibited by Bcl2 but not by caspase inhibitors. Dynamin-related protein 1 (Drp1), a critical mitochondrial fission protein, translocated to mitochondria early during tubular cell injury, and both siRNA knockdown of Drp1 and expression of a dominant-negative Drp1 attenuated mitochondrial fragmentation, cytochrome c release, caspase activation, and apoptosis. Further in vivo analysis revealed that mitochondrial fragmentation also occurred in proximal tubular cells in mice during renal ischemia/reperfusion and cisplatin-induced nephrotoxicity. Notably, both tubular cell apoptosis and acute kidney injury were attenuated by mdivi-1, a newly identified pharmacological inhibitor of Drp1. This study demonstrates a rapid regulation of mitochondrial dynamics during acute kidney injury and identifies mitochondrial fragmentation as what we believe to be a novel mechanism contributing to mitochondrial damage and apoptosis in vivo in mouse models of disease.
 ...
PMID:Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models. 1934 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>