scholarly journals Pharmacological inhibition of Src kinase protects against acute kidney injury in a murine model of renal ischemia/reperfusion

Oncotarget ◽  
2017 ◽  
Vol 8 (19) ◽  
pp. 31238-31253 ◽  
Author(s):  
Chongxiang Xiong ◽  
Xiujuan Zang ◽  
Xiaoxu Zhou ◽  
Lirong Liu ◽  
Monica V. Masucci ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Murine Model ◽  
Ischemia Reperfusion ◽  
Src Kinase ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Pharmacological Inhibition

scholarly journals Post-treatment with JP-1302 protects against renal ischemia/reperfusion-induced acute kidney injury in rats

2019 ◽  
Vol 139 (3) ◽  
pp. 137-142 ◽  
Author(s):  
Takaomi Shimokawa ◽  
Hidenobu Tsutsui ◽  
Takeshi Miura ◽  
Masashi Takama ◽  
Kohei Hayashi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Post Treatment ◽  
Renal Ischemia

scholarly journals Concordant Changes of Plasma and Kidney MicroRNA in the Early Stages of Acute Kidney Injury: Time Course in a Mouse Model of Bilateral Renal Ischemia-Reperfusion

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e93297 ◽  
Author(s):  
Melissa A. Bellinger ◽  
James S. Bean ◽  
Melissa A. Rader ◽  
Kathleen M. Heinz-Taheny ◽  
Jairo S. Nunes ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mouse Model ◽  
Time Course ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Early Stages

scholarly journals Amelioration of testicular damages in renal ischemia/reperfusion by berberine: An experimental study

2019 ◽  
Author(s):  
Firouzeh Gholampour ◽  
Shabnam Malekpour Mansourkhani ◽  
Seyed Mohammad Owji
Keyword(s):  
Acute Kidney Injury ◽  
Plasma Levels ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Plasma Testosterone ◽  
Left Renal Artery ◽  
Functional Disorders ◽  
Urea Nitrogen ◽  
Testosterone Concentration

Background: Ischemic acute kidney injury is associated with an inflammatory reaction. Objective: In the current study, berberine was assessed for its effect on the functional disorders and histological damages of testis induced by renal ischemia/reperfusion (I/R). Materials and Methods: Twenty-eight adult male Wistar rats (260-300 gr) were equally divided into four groups (n = 7/each): sham and I/R groups which received distilled water as well as berberine (BBR) and BBR + I/R groups which received berberine (15 mg/kg/day) orally seven days before the surgery. In both groups of sham and BBR, renal arteries were not clamped. Renal I/R was induced by occluding right and left renal artery for 45 min followed by a 24 hr reperfusion period. Blood samples were taken for determining the plasma levels of creatinine, urea nitrogen, FSH (follicle stimulating hormone), LH (luteinizing hormone), and testosterone. Then the rats were killed under deep anesthesia and the left testis was immediately isolated and preserved. Results: The renal I/R injury led to testicular histological damages accompanied with increased plasma levels of creatinine, urea nitrogen, LH, and FSH, as well decrease of plasma testosterone concentration at the end of 24 hr reperfusion (All p < 0.001, except for FSH p < 0.01). Berberine diminished histological damage to the testis and attenuated the increase in plasma creatinine, urea nitrogen, LH, FSH, and decrease in plasma testosterone concentration in the BBR + I/R group (All p < 0.001). Conclusion: These results suggest that ischemic acute renal failure induces functional disorders and tissue damages in testis of rat, which was improved through the administration of berberine. Key words: Ischemia/reperfusion, Acute kidney injury, Berberine, Testis, LH, FSH.

scholarly journals CBX7 suppression prevents ischemia-reperfusion injury-induced endoplasmic reticulum stress through the Nrf-2/HO-1 pathway

2020 ◽  
Vol 318 (6) ◽  
pp. F1531-F1538
Author(s):  
Ye Zhang ◽  
Jian-Jian Zhang ◽  
Xiu-Heng Liu ◽  
Lei Wang
Keyword(s):  
Acute Kidney Injury ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Translation Initiation Factor ◽  
Heme Oxygenase 1

Renal ischemia-reperfusion injury (I/R) usually occurs in renal transplantation and partial nephrectomy, which could lead to acute kidney injury. However, the effective treatment for renal I/R still remains limited. In the present study, we investigated whether inhibition of chromobox 7 (CBX7) could attenuate renal I/R injury in vivo and in vitro as well as the potential mechanisms. Adult male mice were subjected to right renal ischemia and reperfusion for different periods, both with and without the CBX7 inhibitor UNC3866. In addition, human kidney cells (HK-2) were subjected to a hypoxia/reoxygenation (H/R) process for different periods, both with or without the CBX7 inhibitor or siRNA for CBX7. The results showed that expression of CBX7, glucose regulator protein-78 (GRP78), phosphorylated eukaryotic translation initiation factor-2α (p-eIF2α), and C/EBP homologous protein (CHOP) were increased after extension of I/R and H/R periods. Moreover, overexpression of CBX7 could elevate the expression of CBX7, GRP78, p-eIF2α, and CHOP. However, CBX7 inhibition with either UNC3866 or genetic knockdown led to reduced expression of GRP78, p-eIF2α, and CHOP through nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 activation in I/R and H/R injury. Furthermore, ML385, the Nrf2 inhibitor, could elevate endoplasmic reticulum stress levels, abrogating the protective effects of UNC3866 against renal I/R injury. In conclusion, our results demonstrated that CBX7 inhibition alleviated acute kidney injury by preventing endoplasmic reticulum stress via the Nrf2/HO-1 pathway, indicating that CBX7 inhibitor could be a potential therapeutic target for renal I/R injury.

scholarly journals Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0161315 ◽  
Author(s):  
Marc Johnsen ◽  
Martin Richard Späth ◽  
Martin S. Denzel ◽  
Heike Göbel ◽  
Torsten Kubacki ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Oral Supplementation ◽  
Reperfusion Damage

scholarly journals Acute Kidney Injury Induced Lupus Exacerbation Through the Enhanced Neutrophil Extracellular Traps (and Apoptosis) in Fcgr2b Deficient Lupus Mice With Renal Ischemia Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Wilasinee Saisorn ◽  
Supichcha Saithong ◽  
Pornpimol Phuengmaung ◽  
Kanyarat Udompornpitak ◽  
Thansita Bhunyakarnjanarat ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Neutrophil Extracellular Traps ◽  
Renal Ischemia ◽  
Extracellular Traps ◽  
Renal Ischemia Reperfusion Injury ◽  
Syk Inhibitor

Renal ischemia is the most common cause of acute kidney injury (AKI) that might be exacerbate lupus activity through neutrophil extracellular traps (NETs) and apoptosis. Here, the renal ischemia reperfusion injury (I/R) was performed in Fc gamma receptor 2b deficient (Fcgr2b-/-) lupus mice and the in vitro experiments. At 24 h post-renal I/R injury, NETs in peripheral blood neutrophils and in kidneys were detected using myeloperoxidase (MPO), neutrophil elastase (NE) and citrullinated histone H3 (CitH3), as well as kidney apoptosis (activating caspase-3), which were prominent in Fcgr2b-/- mice more compared to wild-type (WT). After 120 h renal-I/R injury, renal NETs (using MPO and NE) were non-detectable, whereas glomerular immunoglobulin (Ig) deposition and serum anti-dsDNA were increased in Fcgr2b-/- mice. These results imply that renal NETs at 24 h post-renal I/R exacerbated the lupus nephritis at 120 h post-renal I/R injury in Fcgr2b-/- lupus mice. Furthermore, a Syk inhibitor attenuated NETs, that activated by phorbol myristate acetate (PMA; a NETs activator) or lipopolysaccharide (LPS; a potent inflammatory stimulator), more prominently in Fcgr2b-/- neutrophils than the WT cells as determined by dsDNA, PAD4 and MPO. In addition, the inhibitors against Syk and PAD4 attenuated lupus characteristics (serum creatinine, proteinuria, and anti-dsDNA) in Fcgr2b-/- mice at 120 h post-renal I/R injury. In conclusion, renal I/R in Fcgr2b-/- mice induced lupus exacerbation at 120 h post-I/R injury partly because Syk-enhanced renal NETs led to apoptosis-induced anti-dsDNA, which was attenuated by a Syk inhibitor.

scholarly journals Treprostinil, a prostacyclin analog, ameliorates renal ischemia–reperfusion injury: preclinical studies in a rat model of acute kidney injury

2020 ◽  
Author(s):  
Meiwen Ding ◽  
Evelyn Tolbert ◽  
Mark Birkenbach ◽  
Fatemeh Akhlaghi ◽  
Reginald Gohh ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Reperfusion Injury ◽  
Messenger Rna ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury ◽  
Prostacyclin Analog

Abstract Graphical Abstract Background Renal ischemia–reperfusion injury (IRI) is a major factor causing acute kidney injury (AKI). No pharmacological treatments for prevention or amelioration of I/R-induced renal injury are available. Here we investigate the protective effects of treprostinil, a prostacyclin analog, against renal IRI in vivo. Methods Male Sprague Dawley rats were subjected to bilateral renal ischemia (45 min) followed by reperfusion for 1–168 h. Treprostinil (100 ng/kg/min) or placebo was administered subcutaneously for 18–24 h before ischemia. Results Treatment with treprostinil both significantly reduced peak elevation and accelerated the return to baseline levels for serum creatinine and blood urea nitrogen versus I/R-placebo animals following IRI. I/R-treprostinil animals exhibited reduced histopathological features of tubular epithelial injury versus I/R-placebo animals. IRI resulted in a marked induction of messenger RNA coding for kidney injury biomarkers, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin and for pro-inflammatory cytokines chemokine (C-C motif) ligand 2, interleukin 1β, interleukin 6 and intracellular adhesion molecular 1 in animals treated with placebo only relative to sham controls. Upregulation of expression of all these genes was significantly suppressed by treprostinil. Treprostinil significantly suppressed the elevation in renal lipid peroxidation found in the I/R-placebo group at 1-h post-reperfusion. In addition, renal protein expression of cleaved poly(ADP-ribose) polymerase 1 and caspase-3, -8 and -9 in I/R-placebo animals was significantly inhibited by treprostinil. Conclusions This study demonstrates the efficacy of treprostinil in ameliorating I/R-induced AKI in rats by significantly improving renal function early post-reperfusion and by inhibiting renal inflammation and tubular epithelial apoptosis. Importantly, these data suggest that treprostinil has the potential to serve as a therapeutic agent to protect the kidney against IRI in vivo.

scholarly journals Systemic and sustained thioredoxin analogue prevents acute kidney injury and its-associated distant organ damage in renal ischemia reperfusion injury mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kento Nishida ◽  
Hiroshi Watanabe ◽  
Masako Miyahisa ◽  
Yuto Hiramoto ◽  
Hiroto Nosaki ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Lung Injury ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Expression System ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Tnf Α ◽  
Renal Ischemia Reperfusion Injury

AbstractThe mortality of patients with acute kidney injury (AKI) remains high due to AKI associated-lung injury. An effective strategy for preventing both AKI and AKI-associated lung injury is urgently needed. Thioredoxin-1 (Trx) is a redox-active protein that possesses anti-oxidative, anti-apoptotic and anti-inflammatory properties including modulation of macrophage migration inhibitory factor (MIF), but its short half-life limits its clinical application. Therefore, we examined the preventive effect of a long-acting Trx, which is a fusion protein of albumin and Trx (HSA-Trx), against AKI and AKI-associated lung injury. Recombinant HSA-Trx was expressed using a Pichia expression system. AKI-induced lung injury mice were generated by bilateral renal ischemia reperfusion injury (IRI). HSA-Trx administration attenuated renal IRI and its-associated lung injury. Both renal and pulmonary oxidative stress were suppressed by HSA-Trx. Moreover, HSA-Trx inhibited elevations of plasma IL-6 and TNF-α level, and suppressed IL-6–CXCL1/2-mediated neutrophil infiltration into lung and TNF-α-mediated pulmonary apoptosis. Additionally, HSA-Trx suppressed renal IRI-induced MIF expression in kidney and lung. Administration of HSA-Trx resulted in a significant increase in the survival rate of renal IRI mice. Collectively, HSA-Trx could have therapeutic utility in preventing both AKI and AKI-associated lung injury as a consequence of its systemic and sustained multiple biological action.

scholarly journals Mouse model of ischemic acute kidney injury: technical notes and tricks

2012 ◽  
Vol 303 (11) ◽  
pp. F1487-F1494 ◽  
Author(s):  
Qingqing Wei ◽  
Zheng Dong
Keyword(s):  
Acute Kidney Injury ◽  
Mouse Model ◽  
Drug Testing ◽  
Ischemia Reperfusion ◽  
Small Animal ◽  
Kidney Injury ◽  
Experimental Models ◽  
Renal Ischemia

Renal ischemia-reperfusion leads to acute kidney injury (AKI), a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models, both in vitro and in vivo, have been used to study the pathogenic mechanisms of ischemic AKI and to test renoprotective strategies. Among them, the mouse model of renal clamping is popular, mainly due to the availability of transgenic models and the relatively small animal size for drug testing. However, the mouse model is generally less stable, resulting in notable variations in results. Here, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion. We share the lessons and experiences gained from our laboratory in the past decade. We further discuss the technical issues that account for the variability of this model and offer relevant solutions, which may help other investigators to establish a well-controlled, reliable animal model of ischemic AKI.

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