scholarly journals Bone Marrow–Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

2017 ◽  
Vol 41 (5) ◽  
pp. 1736-1752 ◽  
Author(s):  
Felipe Mateus Ornellas ◽  
Débora Santos Ornellas ◽  
Sabrina Vargas Martini ◽  
Raquel Carvalho Castiglione ◽  
Grasiella Maria Ventura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Renal Function ◽  
Biological Markers ◽  
Mononuclear Cells ◽  
Cellular Therapy ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Proliferation Index ◽  
Anti Inflammatory

Background/Aims: We investigated the regenerative capacity of intravenous administration of bone marrow–derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process. Methods: Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by 99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed. Results: Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S. Conclusion: The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy.

scholarly journals Dexmedetomidine Preconditioning Protects Rats from Renal Ischemia–Reperfusion Injury Accompanied with Biphasic Changes of Nuclear Factor-Kappa B Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Naren Bao ◽  
Bing Tang ◽  
Junke Wang
Keyword(s):  
Reperfusion Injury ◽  
Nuclear Factor Kappa B ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Renal Ischemia Reperfusion Injury ◽  
Anti Inflammatory

Acute kidney injury (AKI) is one of the most common and troublesome perioperative complications. Dexmedetomidine (DEX) is a potent α2-adrenoceptor (α2-AR) agonist with anti-inflammatory and renoprotective effects. In this study, a rat renal ischemia–reperfusion injury (IRI) model was induced. At 24 h after reperfusion, the IRI-induced damage and the renoprotection of DEX preconditioning were confirmed both biochemically and histologically. Changes in nuclear factor-kappa B (NF-κB), as well as its downstream anti-inflammatory factor A20 and proinflammatory factor tumor necrosis factor-α (TNF-α), were detected. Atipamezole, a nonselective antagonist, was then added 5 min before the administration of DEX to further analyze DEX’s effects on NF-κB, and another anti-inflammatory medicine, methylprednisolone, was used in comparison with DEX, to further analyze DEX’s effects on NF-κB. Different concentrations of DEX (0 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, and 10 μM) were applied to preincubated human renal tubular epithelial cell line (HK-2) cells in vitro. After anoxia and reoxygenation, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the levels of NF-κB downstream anti-inflammatory cytokines. The results showed that, unlike methylprednisolone, DEX preconditioning led to a time-dependent biphasic change (first activation then inhibition) of NF-κB in the rat renal IRI models that were given 25 μg/kg i.p. It was accompanied by a similarly biphasic change of TNF-α and an early and persistent upregulation of A20. In vitro, DEX’s cellular protection showed a concentration-dependent biphasic change which was protective within the range of 0 to 100 nM but became opposite when concentrations are greater than 1 μM. The changes in the A20 and NF-κB messenger RNA (mRNA) levels were consistent with the renoprotective ability of DEX. In other words, DEX preconditioning protected the rats from renal IRI via regulation biphasic change of NF-κB signaling.

Neuroprotective Effects of Bone Marrow Mononuclear Cells Therapy in a Rat Model of Ischemia Stroke

2020 ◽  
Vol 10 (3) ◽  
pp. 346-351
Author(s):  
Jianfeng Liu ◽  
Yamei Hu ◽  
Gang Li ◽  
Qianlin Zhang ◽  
Jiewen Zhang
Keyword(s):  
Bone Marrow ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Bone Marrow Mononuclear Cells ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Rat Models

Objective: Bone marrow mononuclear cells (BMMCs) are considered a potential approach to promote the recovery of stroke-induced neurological deficit. However, the exact mechanism of BMMCs in nerve function recovery is still unclear. Methods: Adult Sprague-Dawley (SD) rat models of cerebral ischemia-reperfusion injury was established by using thread method. BMMCs were transplanted into rat models. Neurological deficits were evaluated by Longa score scale. Immunohistochemistry assay were employed to examine the expression of GFAP and Nogo-A around the ischemic foci in the right frontal lobe. Caspase-3 activity was examined by Western Blot. Results: Rats in BMMCs group had lessened neurological deficits and cleaved Caspase-3 expression on day 21 after reper-fusion, as well as higher expression of GFAP [(37.62±2.45) vs. (27.62±1.69) and (38.00±1.85) vs. (27.25±1.83), P < 0.05] and lower expression of Nogo-A [(28.88±2.64) vs. (32.50±1.60) and (23.87±2.36) vs. (32.00±1.85), P < 0.05] on day 14 and 21 after reperfusion. Meanwhile, the expression of Nogo-A on day 21 was lower than that on day 14 after reperfusion [(23.87±2.36) vs. (28.88±2.64), P < 0.05] in BMMCs group. Conclusion: These findings suggested that BMMCs treatment could improve the functional recovery of neurological deficits in rats with MCAO, which was probably related to enhanced expression of GFAP and reduced Nogo-A expression and Caspase-3 activity in the ischemic brain tissues.

scholarly journals Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Tian Chen ◽  
Yamei Jiang ◽  
Shihao Xu ◽  
Yin Celeste Cheuk ◽  
Jiyan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pi3k Pathway ◽  
Poly I:C ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Objective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those treated with normal saline, untreated mesenchymal stem cells, mesenchymal stem cells treated with lipopolysaccharide (LPS, pro-inflammatory phenotype) and mesenchymal stem cells treated with polyinosinic-polycytidylic acid (poly[I:C], anti-inflammatory phenotype) respectively. The renal function, histopathological damage, circulating inflammation levels and antioxidant capacity of mice were evaluated. The PI3 kinase p85 (PI3K) inhibitor was added into the conventional mesenchymal stem cell cultures in vitro to observe its effects on the secretion of anti-inflammatory cytokines.Results: Mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) could effectively reduce serum creatinine and blood urea nitrogen, attenuate histopathological damage and apoptosis level, decrease the level of circulating pro-inflammatory cytokines and increase the level of circulating anti-inflammatory cytokines, enhance peroxidase activity and reduce malondialdehyde content at each time point. After the addition of the PI3K inhibitor, the mRNA expression and protein secretion of indoleamine 2,3-dioxygenase 1 and heme oxygenase 1 of various mesenchymal stem cells were significantly reduced, and that of mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) was more obvious.Conclusions: Polyriboinosinic-polyribocytidylic acid (poly[I:C]), a synthetic double-stranded RNA, whose pretreatment induces mesenchymal stem cells to differentiate into the anti-inflammatory phenotype. Anti-inflammatory mesenchymal stem cells induced by poly(I:C) can better protect renal function, alleviate tissue damage, reduce circulating inflammation levels and enhance antioxidant capacity, and achieve stronger anti-inflammatory effects through the TLR3/PI3K pathway.

scholarly journals Riclinoctaose Attenuates Renal Ischemia-Reperfusion Injury by the Regulation of Macrophage Polarization

2021 ◽  
Vol 12 ◽  
Author(s):  
Yang Zhao ◽  
Zhao Ding ◽  
Wenhao Ge ◽  
Junhao Liu ◽  
Xi Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Macrophage Polarization ◽  
Renal Ischemia ◽  
M2 Macrophage ◽  
Mouse Bone Marrow ◽  
M1 Macrophage ◽  
Renal Ischemia Reperfusion Injury

Renal ischemia-reperfusion injury is a major trigger of acute kidney injury and leads to permanent renal impairment, and effective therapies remain unresolved. Riclinoctaose is an immunomodulatory octasaccharide composed of glucose and galactose monomers. Here we investigated whether riclinoctaose protects against renal ischemia-reperfusion injury. In mice, pretreatment with riclinoctaose significantly improved renal function, structure, and the inflammatory response after renal ischemia-reperfusion. Flow cytometry analysis revealed that riclinoctaose inhibited ischemia-reperfusion-induced M1 macrophage polarization and facilitated M2 macrophage recruitment into the kidneys. In isolated mouse bone marrow-derived macrophages, pretreatment with riclinoctaose promoted the macrophage polarization toward M2-like phenotype. The inhibitor of Nrf-2/HO-1 brusatol diminished the effects of riclinoctaose on macrophage polarization. In mice, intravenous injection with riclinoctaose-pretreated bone marrow-derived macrophages also protected against renal ischemia-reperfusion injury. Fluorescence-labeled riclinoctaose specifically bound to the membrane of macrophages. Interfering with mDC-SIGN blocked the riclinoctaose function on M2 polarization of macrophages, consequently impairing the renoprotective effect of riclinoctaose. Our results revealed that riclinoctaose is a potential therapeutic agent in preventing renal ischemia-reperfusion injury.

O2 metabolites cause reperfusion injury after short but not prolonged renal ischemia

1987 ◽  
Vol 253 (4) ◽  
pp. F685-F691 ◽  
Author(s):  
S. L. Linas ◽  
D. Whittenburg ◽  
J. E. Repine
Keyword(s):  
Renal Function ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Cellular Events ◽  
Perfusion Flow ◽  
Biochemical Assessment ◽  
Perfusion Flow Rate

Toxic O2 metabolites have been postulated to contribute to renal ischemia-reperfusion injury, but their biochemical assessment and contribution as a function of the duration of ischemia is unclear. To address this issue we measured renal function and renal cortical glutathione levels following 20, 30, or 45 min of ischemia in situ and then 60 min of reperfusion by the isolated kidney technique. Increasing durations of ischemia were associated with progressive decreases in perfusion flow rate, glomerular filtration rate, tubular Na reabsorption, and renal cortical glutathione following reperfusion. However, reperfusion following simultaneous addition of the permeable O2 metabolite scavenger dimethylthiourea (DMTU; but not urea) prevented glutathione consumption and attenuated reperfusion-induced injury after 20 and 30 min of ischemia. In contrast, reperfusion with DMTU prevented glutathione consumption but did not improve renal function after 45 min of ischemia. Similarly, reperfusion with dimethyl sulfoxide also attenuated renal injury after 20 and 30 min, but not after 45 min of ischemia. Thus reperfusion of kidneys made ischemic for 20 or 30 min is associated with decreases in tissue glutathione and renal function that were both inhibitable by addition of O2 metabolite scavengers during reperfusion. In contrast, addition of O2 metabolite scavengers during reperfusion of kidneys previously made ischemic for 45 min prevented decreases in glutathione but did not improve renal function. We conclude that O2 metabolites formed during reperfusion contribute to functional impairment in kidneys made ischemic for short durations up to 30 min) but that after prolonged ischemia (greater than 30 min) injury is primarily mediated by non-O2 metabolite-dependent cellular events.

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