scholarly journals Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Marco A. C. de Resende ◽  
Alberto V. Pantoja ◽  
Bruno M. Barcellos ◽  
Eduardo P. Reis ◽  
Thays D. Consolo ◽  
...  
Keyword(s):  
Renal Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Arterial Occlusion ◽  
Kidney Injury ◽  
Ischemic Postconditioning ◽  
Tubular Damage ◽  
Ketamine Infusion ◽  
Renal Histology

Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI.Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology.Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG.Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model.

scholarly journals Targeting HIF-1α to Prevent Renal Ischemia-Reperfusion Injury: Does It Work?

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Kapil Sethi ◽  
Kenny Rao ◽  
Damien Bolton ◽  
Oneel Patel ◽  
Joseph Ischia
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Arterial Occlusion ◽  
Small Animal ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Metabolic Adaptation ◽  
Critical Ischemia

Partial nephrectomy (open or minimally invasive) usually requires temporary renal arterial occlusion to limit intraoperative bleeding and improve access to intrarenal structures. This is a time-critical step due to the critical ischemia period of renal tissue. Prolonged renal ischemia may lead to irreversible nephron damage in the remaining tissue and, ultimately, chronic kidney disease. This is potentiated by the incompletely understood ischemia-reperfusion injury (IRI). A key mechanism in IRI prevention appears to be the upregulation of an intracellular transcription protein, Hypoxia-Inducible Factor (HIF). HIF mediates metabolic adaptation, angiogenesis, erythropoiesis, cell growth, survival, and apoptosis. Upregulating HIF-1α via ischemic preconditioning (IPC) or drugs that simulate hypoxia (hypoxia-mimetics) has been investigated as a method to reduce IRI. While many promising chemical agents have been trialed for the prevention of IRI in small animal studies, all have failed in human trials. The aim of this review is to highlight the techniques and drugs that target HIF-1α and ameliorate IRI associated with renal ischemia. Developing a technique or drug that could reduce the risk of acute kidney injury associated with renal IRI would have an immediate worldwide impact on multisystem surgeries that would otherwise risk ischemic tissue injury.

scholarly journals Netrin-1 and kidney injury. I. Netrin-1 protects against ischemia-reperfusion injury of the kidney

2008 ◽  
Vol 294 (4) ◽  
pp. F739-F747 ◽  
Author(s):  
Weiwei Wang ◽  
W. Brian Reeves ◽  
Ganesan Ramesh
Keyword(s):  
Cell Activation ◽  
Ischemia Reperfusion Injury ◽  
Vascular Endothelial Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Endothelial Cell Activation ◽  
Protein Levels ◽  
Peritubular Capillaries ◽  
The Impact

Endogenous mechanisms exist to limit inflammation. One such molecule is netrin. This study examined the impact of ischemia-reperfusion (I/R) on netrin expression and the role of netrin in preventing renal inflammation and injury. All three isoforms of netrin (1, 3, and 4) are expressed in normal kidney. I/R significantly downregulated netrin-1 and -4 mRNA expression, whereas expression of netrin-3 was moderately upregulated at 24 h of reperfusion. The netrin receptor UNC5B mRNA increased at 3 h and but decreased at later time points. Expression of a second netrin receptor, DCC, was not altered significantly. I/R was associated with dramatic changes in netrin-1 protein abundance and localization. Netrin-1 protein levels increased between 3 and 24 h after reperfusion. Immunolocalization showed an interstitial distribution of netrin-1 in sham-operated kidneys which colocalized with Von Willebrand Factor suggesting the presence of netrin-1 in peritubular capillaries. After I/R, interstitial netrin-1 expression decreased and netrin-1 appeared in tubular epithelial cells. By 72 h after reperfusion, netrin-1 reappeared in the interstitium while tubular epithelial staining decreased significantly. Downregulation of netrin-1 in the interstitium corresponded with increased MCP-1 and IL-6 expression and infiltration of leukocytes into the reperfused kidney. Administration of recombinant netrin-1 significantly improved kidney function (blood urea nitrogen: 161 ± 7 vs. 104 ± 24 mg/dl, creatinine: 1.3 ± 0.07 vs. 0.75 ± 0.16 mg/dl, P < 0.05 at 24 h) and reduced tubular damage and leukocyte infiltration in the outer medulla. These results suggest that downregulation of netrin-1 in vascular endothelial cells may promote endothelial cell activation and infiltration of leukocytes into the kidney thereby enhancing tubular injury.

scholarly journals Antithrombin nanoparticles improve kidney reperfusion and protect kidney function after ischemia-reperfusion injury

2015 ◽  
Vol 308 (7) ◽  
pp. F765-F773 ◽  
Author(s):  
Junjie Chen ◽  
Chandu Vemuri ◽  
Rohun U. Palekar ◽  
Joseph P. Gaut ◽  
Matthew Goette ◽  
...  
Keyword(s):  
Renal Function ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Vascular Endothelial Cell ◽  
Kidney Injury ◽  
Warm Ischemia ◽  
Thrombin Inhibitor ◽  
Direct Role ◽  
Creatinine Concentration

In the extension phase of acute kidney injury, microvascular thrombosis, inflammation, vasoconstriction, and vascular endothelial cell dysfunction promote progressive damage to renal parenchyma after reperfusion. In this study, we hypothesized that direct targeting and pharmaceutical knockdown of activated thrombin at the sites of injury with a selective nanoparticle (NP)-based thrombin inhibitor, PPACK (phenylalanine-proline-arginine-chloromethylketone), would improve kidney reperfusion and protect renal function after transient warm ischemia in rodent models. Saline- or plain NP-treated animals were employed as controls. In vivo 19F magnetic resonance imaging revealed that kidney nonreperfusion was evident within 3 h after global kidney reperfusion at 34 ± 13% area in the saline group and 43 ± 12% area in the plain NP group and substantially reduced to 17 ± 4% (∼50% decrease, P < 0.05) in the PPACK NP pretreatment group. PPACK NP pretreatment prevented an increase in serum creatinine concentration within 24 h after ischemia-reperfusion, reflecting preserved renal function. Histologic analysis illustrated substantially reduced intrarenal thrombin accumulation within 24 h after reperfusion for PPACK NP-treated kidneys (0.11% ± 0.06%) compared with saline-treated kidneys (0.58 ± 0.37%). These results suggest a direct role for thrombin in the pathophysiology of AKI and a nanomedicine-based preventative strategy for improving kidney reperfusion after transient warm ischemia.

Trehalose attenuates renal ischemia-reperfusion injury by enhancing autophagy and inhibiting oxidative stress and inflammation

2020 ◽  
Vol 318 (4) ◽  
pp. F994-F1005
Author(s):  
Suwen Liu ◽  
Yunwen Yang ◽  
Huiping Gao ◽  
Ning Zhou ◽  
Peipei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Renal Histology ◽  
Hypoxia Reoxygenation

Renal ischemia-reperfusion (IR) injury is one of the most common acute kidney injuries, but there is still a lack of effective treatment in the clinical setting. Trehalose (Tre), a natural disaccharide, has been demonstrated to protect against oxidative stress, inflammation, and apoptosis. However, whether it could protect against IR-induced renal injury needs to be investigated. In an in vivo experiment, C57BL/6J mice were pretreated with or without Tre (2 g/kg) through a daily single intraperitoneal injection from 3 days before renal IR surgery. Renal function, apoptosis, oxidative stress, and inflammation were analyzed to evaluate kidney injury. In an in vitro experiment, mouse proximal tubular cells were treated with or without Tre under a hypoxia/reoxygenation condition. Western blot analysis, autophagy flux detection, and apoptosis assay were performed to evaluate the level of autophagy and antiapoptotic effect of Tre. The in vivo results showed that the renal damage induced by IR was ameliorated by Tre treatment, as renal histology and renal function were improved and the enhanced protein levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were blocked. Moreover, autophagy was activated by Tre pretreatment along with inhibition of the IR injury-induced apoptosis, oxidative stress, and inflammation. The in vitro results showed that Tre treatment activated autophagy and protected against hypoxia/reoxygenation-induced tubular cell apoptosis and oxidative stress. Our results demonstrated that Tre protects against IR-induced renal injury, possibly by enhancing autophagy and blocking oxidative stress, inflammation, and apoptosis, suggesting its potential use for the clinical treatment of renal IR injury.

scholarly journals Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation

2008 ◽  
Vol 23 (suppl 1) ◽  
pp. 42-46 ◽  
Author(s):  
Silvio Tucci Junior ◽  
Roberto Marins de Carvalho ◽  
Fábia Martins Celini ◽  
Adauto José Cologna ◽  
Haylton Jorge Suaid ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Renal Function ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Renal Ischemia ◽  
Control Group ◽  
Ischemia And Reperfusion Injury ◽  
Mda Content

PURPOSE: To evaluate the influence of chlorpromazine (CPZ) on renal function and lipid peroxidation in a rat model of kidney ischemia/reperfusion injury. METHODS: Forty eight Wistar rats underwent a laparotomy for hilar clamping of left kidney with a bulldog clamp for 60 minutes followed by organ reperfusion and contralateral nephrectomy. Of these, 26 received 3mg/kg of CPZ intravenously 15 minutes before renal ischemia (G-E) while the remaining 22 were used as ischemic control group (G-C). Eleven rats of G-E and 8 of G-C were followed for blood urea nitrogen and creatinine determinations before renal ischemia and at 1st, 4th and 7th postoperative days. Samplings of left renal tissue were obtained at 5 minutes (5 rats from each group) and 24 hours (9 G-C and 10 of G-E) of reperfusion for malondialdehy (MDA) content determination. Controls of renal MDA content were determined in kidneys harvested from 6 additional normal rats. RESULTS: Acute renal failure occurred in all animals but levels of BUN and creatinine were significantly lower in G-E (p<0.001). MDA content rose strikingly at 5 minutes of reperfusion in both groups (p>0.05) and returned near to normal levels 24 hours later. CONCLUSION: CPZ conferred partial protection of renal function to kidneys submitted to ischemia/reperfusion injury that seems to be not dependent on inhibition of lipid peroxidation.

scholarly journals ADAMTS13 protects mice against renal ischemia-reperfusion injury by reducing inflammation and improving endothelial function

2019 ◽  
Vol 316 (1) ◽  
pp. F134-F145 ◽  
Author(s):  
Suhan Zhou ◽  
Shan Jiang ◽  
Jie Guo ◽  
Nan Xu ◽  
Qin Wang ◽  
...  
Keyword(s):  
Renal Function ◽  
Endothelial Function ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Renal Protection ◽  
Renal Ischemia Reperfusion Injury ◽  
Microvascular Endothelial

Acute kidney injury (AKI) is a serious condition without efficient therapeutic options. Recent studies have indicated that recombinant human a disintegrin and metalloprotease with thrombospondin motifs 13 (rhADAMTS13) provides protection against inflammation. Therefore, we hypothesized that ADAMTS13 might protect against AKI by reducing inflammation. Bilateral renal ischemia-reperfusion injury (I/R) was used as AKI models in this study. Prophylactic infusion of rhADAMTS13 was employed to investigate potential mechanisms of renal protection. Renal function, inflammation, and microvascular endothelial function were assessed after 24 h of reperfusion. Our results showed that I/R mice increased plasma von Willebrand factor levels but decreased ADAMTS13 expression. Administration of rhADAMTS13 to I/R mice recovered renal function, histological injury, and apoptosis. Renal inflammation was reduced by rhADAMTS13, accompanied with the downregulation of p38/extracellular signal-regulated protein kinase phosphorylation and cyclooxygenase-2 expression. rhADAMTS13 restored vasodilation in afferent arterioles in I/R mice. Furthermore, rhADAMTS13 treatment enhanced phosphorylation of Akt at Ser473 and eNOS at Ser1177. Administration of the Akt pathway inhibitor wortmannin reduced the protective effect of rhADAMTS13. Our conclusions are that treatment with rhADAMTS13 ameliorates renal I/R injury by reducing inflammation, tubular cell apoptosis, and improving microvascular endothelial dysfunction. rhADAMTS13 could be a promising strategy to treat AKI in clinical settings.

scholarly journals RTA-408 Protects Kidney from Ischemia-Reperfusion Injury in Mice via Activating Nrf2 and Downstream GSH Biosynthesis Gene

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Peng Han ◽  
Zhiqiang Qin ◽  
Jingyuan Tang ◽  
Zhen Xu ◽  
Ran Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Function ◽  
Reperfusion Injury ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Ros Production ◽  
Antioxidant Genes

Acute kidney injury (AKI) induced by ischemia-reperfusion is a critical conundrum in many clinical settings. Here, this study aimed to determine whether and how RTA-408, a novel oleanane triterpenoid, could confer protection against renal ischemia-reperfusion injury (IRI) in male mice. Mice treated with RTA-408 undergoing unilateral ischemia followed by contralateral nephrectomy had improved renal function and histological outcome, as well as decreased apoptosis, ROS production, and oxidative injury marker compared with vehicle-treated mice. Also, we had found that RTA-408 could strengthen the total antioxidant capacity by increasing Nrf2 nuclear translocation and subsequently increased Nrf2 downstream GSH-related antioxidant gene expression and activity. In vitro study demonstrated that GSH biosynthesis enzyme GCLc could be an important target of RTA-408. Furthermore, Nrf2-deficient mice treated with RTA-408 had no significant improvement in renal function, histology, ROS production, and GSH-related gene expression. Thus, by upregulating Nrf2 and its downstream antioxidant genes, RTA-408 presents a novel and potential approach to renal IRI prevention and therapy.

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