scholarly journals Rosiglitazone Suppresses Renal Crystal Deposition by Ameliorating Tubular Injury Resulted from Oxidative Stress and Inflammatory Response via Promoting the Nrf2/HO-1 Pathway and Shifting Macrophage Polarization

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Hongyan Lu ◽  
Xifeng Sun ◽  
Min Jia ◽  
Fa Sun ◽  
Jianguo Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Macrophage Polarization ◽  
Glyoxylic Acid ◽  
Adhesion Assay ◽  
Tubular Injury ◽  
Crystal Deposition ◽  
Crystal Adhesion

Oxidative stress and inflammatory response are closely related to nephrolithiasis. This study is aimed at exploring whether rosiglitazone (ROSI), a regulator of macrophage (Mp) polarization, could reduce renal calcium oxalate (CaOx) deposition by ameliorating oxidative stress and inflammatory response. Male C57 mice were equally and randomly divided into 7 groups. Kidney sections were collected on day 5 or day 8 after treatment. Pizzolato staining and polarized light optical microscopy were used to detect crystal deposition. PAS staining and TUNEL assay were performed to assess the tubular injury and cell apoptosis, respectively. Gene expression was assessed by immunohistochemistry, immunofluorescence, ELISA, qRT-PCR, and Western blot. The reactive oxygen species (ROS) level was assessed using a fluorescence microplate and fluorescence microscope. Hydrogen peroxide (H2O2), malonaldehyde (MDA), and glutathione (GSH) were evaluated to determine oxidative stress. Lactic dehydrogenase (LDH) activity was examined to detect cell injury. Adhesion of CaOx monohydrate (COM) crystals to HK-2 cells was detected by crystal adhesion assay. HK-2 cell death or renal macrophage polarization was assessed by flow cytometry. In vivo, renal crystal deposition, tubular injury, crystal adhesion, cell apoptosis, oxidative stress, and inflammatory response were significantly increased in the 7-day glyoxylic acid- (Gly-) treated group but were decreased in the ROSI-treated groups, especially in the groups pretreated with ROSI. Moreover, ROSI significantly reduced renal Mp aggregation and M1Mp polarization but significantly enhanced renal M2Mp polarization. In vitro, ROSI significantly suppressed renal injury, apoptosis, and crystal adhesion of HK-2 cells and markedly shifted COM-stimulated M1Mps to M2Mps, presenting an anti-inflammatory effect. Furthermore, ROSI significantly suppressed oxidative stress by promoting the Nrf2/HO-1 pathway in HK-2 cells. These findings indicate that ROSI could ameliorate renal tubular injury that resulted from oxidative stress and inflammatory response by suppressing M1Mp polarization and promoting M2Mp polarization. Therefore, ROSI is a potential therapeutic and preventive drug for CaOx nephrolithiasis.

scholarly journals Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis

2021 ◽  
Vol 16 (1) ◽  
pp. 537-543
Author(s):  
Mei Zhang ◽  
Jing Yuan ◽  
Rong Dong ◽  
Jingjing Da ◽  
Qian Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Tubular Injury ◽  
Jnk Pathway ◽  
Pathway Activation

Abstract Background Hyperhomocysteinemia (HHcy) plays an important role in the progression of many kidney diseases; however, the relationship between HHcy and ischemia-reperfusion injury (IRI)-induced acute kidney injury (IRI-induced AKI) is far from clear. In this study, we try to investigate the effect and possible mechanisms of HHcy on IRI-induced AKI. Methods Twenty C57/BL6 mice were reared with a regular diet or high methionine diet for 2 weeks (to generate HHcy mice); after that, mice were subgrouped to receive sham operation or ischemia-reperfusion surgery. Twenty four hour after reperfusion, serum creatinine, blood urea nitrogen, and Malondialdehyde (MDA) were measured. H&E staining for tubular injury, western blot for γH2AX, JNK, p-JNK, and cleaved caspase 3, and TUNEL assay for tubular cell apoptosis were also performed. Results Our results showed that HHcy did not influence the renal function and histological structure, as well as the levels of MDA, γH2AX, JNK, p-JNK, and tubular cell apoptosis in control mice. However, in IRI-induced AKI mice, HHcy caused severer renal dysfunction and tubular injury, higher levels of oxidative stress, DNA damage, JNK pathway activation, and tubular cell apoptosis. Conclusion Our results demonstrated that HHcy could exacerbate IRI-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, JNK pathway activation, and consequent apoptosis.

scholarly journals SNHG3 cooperates with ELAVL2 to modulate cell apoptosis and extracellular matrix accumulation by stabilizing SNAI2 in human trabecular meshwork cells under oxidative stress

2020 ◽  
Author(s):  
Sizhen Li ◽  
Qingsong Yang ◽  
Zixiu Zhou ◽  
Min Fu ◽  
Xiaodong Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Intraocular Pressure ◽  
Oxidative Damage ◽  
Trabecular Meshwork ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Quantitative Polymerase Chain Reaction ◽  
Subcellular Fractionation ◽  
Cell Counting

Abstract Background: Glaucoma is the main reason for irreversible blindness, and pathological increased intraocular pressure is the leading risk factor for glaucoma. It is reported that trabecular meshwork cell injury is closely associated with the elevated intraocular pressure. The current study aimed to investigate the role of SNHG3 in human trabecular meshwork (HTM) cells under oxidative stress. Methods: A series of experiments including real-time quantitative polymerase chain reaction (RT-qPCR), subcellular fractionation assay, western blot analysis, cell counting kit-8 (CCK-8) assay, RNA pull down, flow cytometry analysis, and RIP assay were employed to explore the biological function and regulatory mechanism of SNHG3 in HTM cells under oxidative stress.Results: First, we observed that H2O2 induced SNHG3 upregulation in HTM cells. Then, we found that SNHG3 silencing alleviated H2O2-induced oxidative damage in HTM cells. Moreover, SNAI2 knockdown alleviated the oxidative damage induced by H2O2 in HTM cells. Mechanistically, SNHG3 bound with ELAVL2 to stabilize SNAI2. Finally, SNAI2 overexpression counteracted the effect of SNHG3 silencing on H2O2-induced HTM cells. Conclusion: Our results demonstrated that SNHG3 cooperated with ELAVL2 to modulate cell apoptosis and extracellular matrix (ECM) accumulation by stabilizing SNAI2 in HTM cells under oxidative stress.

scholarly journals Podocyte and tubular involvement in AngioJet-induced kidney injury

2019 ◽  
Author(s):  
Raquel Esteras ◽  
Pablo Cannata-Ortiz ◽  
Marta del Palacio-Tamarit ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adaptive Response ◽  
Mechanical Thrombectomy ◽  
Cell Injury ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Histological Evidence ◽  
Cellular Targets ◽  
Percutaneous Mechanical Thrombectomy ◽  
Renal Biopsies

Abstract The AngioJet technique combines localized thrombolysis and percutaneous mechanical thrombectomy (PMT). However, PMT may cause acute kidney injury (AKI), which has been ascribed to severe mechanical haemolysis, although no renal biopsies have been reported. We now report the first renal biopsy in a patient with AKI following PMT. There is histological evidence of haemoglobin (Hb)-induced tubular injury and podocyte stress characterized by intracellular Hb and staining for ferritin and hemo-oxygenase-1, suggestive of an adaptive response to oxidative stress. This confirms that Hb is involved in kidney cell injury and supports the existence of several different kidney cellular targets.

Hydroxycitric Acid Inhibits Renal Calcium Oxalate Deposition by Reducing Oxidative Stress and Inflammation

2020 ◽  
Vol 20 (7) ◽  
pp. 527-535 ◽  
Author(s):  
Xiao Liu ◽  
Peng Yuan ◽  
Xifeng Sun ◽  
Zhiqiang Chen
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Calcium Oxalate ◽  
Tubular Injury ◽  
Calcium Oxalate Crystals ◽  
Calcium Oxalate Crystal ◽  
Crystal Deposition ◽  
Qrt Pcr ◽  
Hydroxycitric Acid ◽  
Oxalate Crystals

Objective: The study aimed to evaluate the preventive effects of hydroxycitric acid（HCA） for stone formation in the glyoxylate-induced mouse model. Materials and methods: Male C57BL/6J mice were divided into a control group, glyoxylate(GOX) 100 mg/kg group, a GOX+HCA 100 mg/kg group, and a GOX+HCA 200 mg/kg group. Blood samples and kidney samples were collected on the eighth day of the experiment. We used Pizzolato staining and a polarized light microscope to examine crystal formation and evaluated oxidative stress via the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the expression of monocyte chemotactic protein-1(MCP-1), nuclear factor-kappa B (NF κ B), interleukin-1 β (IL-1 β) and interleukin-6 (IL-6) messenger RNA (mRNA). The expression of osteopontin (OPN) and a cluster of differentiation-44(CD44) were detected by immunohistochemistry and qRT-PCR. In addition, periodic acid Schiff (PAS) staining and TUNEL assay were used to evaluate renal tubular injury and apoptosis. Results: HCA treatment could reduce markers of renal impairment (Blood Urea Nitrogen and serum creatinine). There was significantly less calcium oxalate crystal deposition in mice treated with HCA. Calcium oxalate crystals induced the production of reactive oxygen species and reduced the activity of antioxidant defense enzymes. HCA attenuated oxidative stress induced by calcium oxalate crystallization. HCA had inhibitory effects on calcium oxalate-induced inflammatory cytokines, such as MCP-1, IL- 1 β, and IL-6. In addition, HCA alleviated tubular injury and apoptosis caused by calcium oxalate crystals. Conclusion: HCA inhibits renal injury and calcium oxalate crystal deposition in the glyoxylate-induced mouse model through antioxidation and anti-inflammation.

scholarly journals MP67-07 THE PROTECTIVE EFFECTS OF PROPOLIS ON OXIDATIVE STRESS AND CRYSTAL DEPOSITION WITH HYPEROXALURIA INDUCED TUBULAR CELL INJURY IN RAT MODEL

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Kamil Fehmi Narter ◽  
Alper Kafkasli ◽  
Oguz Ozturk ◽  
Ozgur Yazici ◽  
Bilal Hamarat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Cell Injury ◽  
Tubular Cell ◽  
Protective Effects ◽  
Crystal Deposition

Luteolin Attenuates Diabetic Nephropathy through Suppressing Inflammatory Response and Oxidative Stress by Inhibiting STAT3 Pathway

2020 ◽  
Author(s):  
Miaoyuan Zhang ◽  
Liyu He ◽  
Jingsong Liu ◽  
Lin Zhou
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Inflammatory Response ◽  
Animal Experiments ◽  
Pathological Feature ◽  
Tubular Injury ◽  
Oral Gavage ◽  
Stat3 Pathway ◽  
Kidney Protection ◽  
And Oxidative Stress

Abstract Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). DN has many pathological changes, but tubular injury is considered to be a crucial pathological feature and plays a key role in the progression of DN. Accumulating studies have confirmed that Luteolin (3,4,5,7-tetrahydroxyflavone, Lut) possesses anti-inflammatory and antioxidant activities, which may play a role in kidney protection in DN. Objectives This paper described the effects of Lut on appropriated tubular injury in the kidneys of db/db mice and searched the possible mechanisms underlying the kidney protection effect in DN. Methods Twelve-week-old male C57BL/6 J db/db and C57BL/6 J db/m mice were used for the animal experiments. They were organized into the following five groups for the animal experiments: a db/m group (control, n=6); a db/db group(n=8) ; a db/db group receiving Lut (10 mg/kg/day, n=8)treatment by oral gavage; a db/db group receiving stattic (a selective STAT3 inhibitor,50 mg/Kg/day, n=8) treatment by oral gavage and a db/db group receiving both stattic and Lut treatment by oral gavage. Results In this study, we found that Lut might ameliorate glomerular sclerosis and interstitial fibrosis in DN mouse models through inhibiting the inflammatory response and oxidative stress. And it might play its biological function mainly through repressing the STAT3 activation. Conclusions Lut attenuates DN mainly via suppression of inflammatory response and oxidative response. STAT3 pathway is the potential target, which ultimately reduces renal fibrosis and delays the progress of DN.

scholarly journals USP10 alleviates sepsis-induced acute kidney injury by regulating Sirt6-mediated Nrf2/ARE signaling pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Fei Gao ◽  
Mingjiang Qian ◽  
Guoyue Liu ◽  
Wanping Ao ◽  
Dahua Dai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Epithelial Cell ◽  
Western Blot ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Renal Tubular Epithelial Cell ◽  
Renal Tubular

Abstract Background Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. H2O2, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis. Results In this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury. Conclusions This study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.

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