NGAL attenuates renal ischemia/reperfusion injury through autophagy activation and apoptosis inhibition in rats

Zhang, Yali; Qiao, Shu-Kai; Wang, Rongying; Guo, Xiaonan

doi:10.1016/j.cbi.2018.04.018

Cited by 33 publications

(24 citation statements)

References 29 publications

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“…Additionally, it not only marks injury but mediates cell repair, too [18]. NGAL not only serves as early injury marker, but also seems to play a role in the transition from acute to chronic kidney disease [19] and its exogenous application experimentally attenuated IRI in rats [20].…”

Section: Histopathological Evaluationmentioning

confidence: 99%

“Point of no return” in unilateral renal ischemia reperfusion injury in mice

et al. 2020

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Background: In the past years evidence has been growing about the interconnection of chronic kidney disease and acute kidney injury. The underlying pathophysiological mechanisms remain unclear. We hypothesized, that a threshold ischemia time in unilateral ischemia/reperfusion injury sets an extent of ischemic tubule necrosis, which as "point of no return" leads to progressive injury. This progress is temporarily associated by increased markers of inflammation and results in fibrosis and atrophy of the ischemic kidney. Methods: Acute tubule necrosis was induced by unilateral ischemia/reperfusion injury in male C57BL/6 N mice with different ischemia times (15, 25, 35, and 45 min). At multiple time points between 15 min and 5 weeks we assessed gene expression of markers for injury, inflammation, and fibrosis, histologically the injury of tubules, cell death (TUNEL), macrophages, neutrophil influx and kidney atrophy. Results: Unilateral ischemia for 15 and 25 min induced upregulation of markers for injury after reperfusion for 24 h but no upregulation after 5 weeks. None of the markers for inflammation or fibrosis were upregulated after ischemia for 15 and 25 min at 24 h or 5 weeks on a gene expression level, except for Il-6. Ischemia for 35 and 45 min consistently induced upregulation of markers for inflammation, injury, and partially of fibrosis (Tgf-β1 and Col1a1) at 24 h and 5 weeks. The threshold ischemia time for persistent injury of 35 min induced a temporal association of markers for inflammation and injury with peaks between 6 h and 7 d along the course of 10 d. This ischemia time also induced persistent cell death (TUNEL) throughout observation for 5 weeks with a peak at 6 h and progressing kidney atrophy beginning 7 d after ischemia. Conclusions: This study confirms the evidence of a threshold extent of ischemic injury in which markers of injury, inflammation and fibrosis do not decline to baseline but remain upregulated assessed in long term outcome (5 weeks). Excess of this threshold as "point of no return" leads to persistent cell death and progressing atrophy and is characterized by a temporal association of markers for inflammation and injury.

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Section: Histopathological Evaluationmentioning

confidence: 99%

“Point of no return” in unilateral renal ischemia reperfusion injury in mice

et al. 2020

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“…[4][5][6] Ischemic injury is the main cause of AKI, although at present, there is a significant lack of therapeutic options for treatment. 7 However, research has provided strong evidence that oxidative stress and inflammation are major contributors to the pathogenesis of ischemic AKI. [8][9][10][11] Ischemia/reperfusion (I/R) injury can lead to the production of large amounts of reactive oxygen species (ROS) in tubular epithelial cells (TECs), thus triggering mitochondrial damage and lipid peroxidation and causing devastating cell damage.…”

Section: Introductionmentioning

confidence: 99%

Porous Se@SiO<sub>2</sub> nanospheres attenuate ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and inflammation by antioxidative stress

Zheng¹,

Deng²,

Qi³

et al. 2018

IJN

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ObjectivesAcute kidney injury (AKI) is a growing global health concern, and is associated with high rates of mortality and morbidity in intensive care units. Se is a trace element with antioxidant properties. This study aimed to determine whether porous Se@SiO2 nanospheres could relieve oxidative stress and inflammation in ischemia/reperfusion (I/R)-induced AKI.MethodsMale 6- to 8-week-old C57bl/6 mice were divided into four groups: sham + saline, sham + Se@SiO2, I/R + saline, and I/R + Se@SiO2. Mice in the I/R groups experienced 30 minutes of bilateral renal I/R to induce an AKI. Porous Se@SiO2 nanospheres (1 mg/kg) were intraperitoneally injected into mice in the I/R + Se@SiO2 group 2 hours before I/R, and the same dose was injected every 12 hours thereafter. Hypoxia/reoxygenation (H/R) was used to mimic I/R in vitro. PBS was used as a control treatment. Human kidney 2 cells were seeded into 12-well plates (5×105 cells/well) and divided into four groups: control + PBS group, control + Se@SiO2 group, H/R + PBS group, and H/R + Se@SiO2 group (n=3 wells). We then determined the expression levels of ROS, glutathione, inflammatory cytokines and proteins, fibrosis proteins, and carried out histological analysis upon kidney tissues.ResultsIn vitro, intervention with porous Se@SiO2 nanospheres significantly reduced levels of ROS (P<0.05), inflammatory cytokines (P<0.05), and inflammation-associated proteins (P<0.05). In vivo, tubular damage, cell apoptosis, and interstitial inflammation during AKI were reduced significantly following treatment with porous Se@SiO2 nanospheres. Moreover, the occurrence of fibrosis and tubular atrophy after AKI was attenuated by porous Se@SiO2 nanospheres.ConclusionPorous Se@SiO2 nanospheres exhibited a protective effect in I/R-induced AKI by resisting oxidative stress and inflammation. This suggests that porous Se@SiO2 nanospheres may represent a new therapeutic method for AKI.

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“…It may be that renal tubules are more sensitive to hypoxia than glomerulus; as a result, renal tubules are damaged before glomeruli [19]. Autophagy is another vital link in the study of pathological changes after myocardial infarction, playing a vital role to protect the kidney or heart from injury [26,27].…”

Section: Discussionmentioning

confidence: 99%

Adaptive Autophagy Offers Cardiorenal Protection in Rats with Acute Myocardial Infarction

Feng

Jiang

Chen

et al. 2020

Cardiology Research and Practice

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Objective. Understanding the multifactorial changes involved in the kidney and heart after acute myocardial infarction (AMI) is prerequisite for further mechanisms and early intervention, especially autophagy changes. Here, we discussed the role of adaptive autophagy in the heart and kidney of rats with AMI. Methods. A rat model of AMI was established by ligating the left anterior descending branch of the coronary artery. Animals were sacrificed at 2 and 4 weeks after the operation to assess the morphological and functional changes of the heart and kidney, as well as the autophagy pathway. In vitro, HK-2 and AC16 cell injuries and the autophagy pathway were assayed after autophagy was inhibited by 3-methyladenine (3-MA) in a hypoxia incubator. Results. We found that the left ventricular systolic pressure (LVSP) significantly decreased in the model group at weeks 2 and 4. At weeks 2 and 4, the level of urinary kidney injury molecule 1 (uKIM1) of the model group was significantly higher than the sham group. At week 4, urinary neutrophil gelatinase-associated lipocalcin (uNGAL) and urinary albumin also significantly increased. At week 2, microtubule-associated protein 1 light chain 3-II (LC3-II), ATG5, and Beclin1 were significantly elevated in the heart and kidney compared with the sham-operated rats, but there was no change in p62 levels. At week 4, LC3-II did not significantly increase and p62 levels significantly increased. In addition, 3-MA markedly increased KIM1, NGAL, and the activity of caspase-3 in the hypoxic HK-2 and AC16 cell. Conclusion. Autophagy will undergo adaptive changes and play a protective role in the heart and kidney of rats after AMI.

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NGAL attenuates renal ischemia/reperfusion injury through autophagy activation and apoptosis inhibition in rats

Cited by 33 publications

References 29 publications

“Point of no return” in unilateral renal ischemia reperfusion injury in mice

“Point of no return” in unilateral renal ischemia reperfusion injury in mice

Porous Se@SiO<sub>2</sub> nanospheres attenuate ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and inflammation by antioxidative stress

Adaptive Autophagy Offers Cardiorenal Protection in Rats with Acute Myocardial Infarction

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