scholarly journals Catalytic Antioxidants in the Kidney

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 130
Author(s):  
Yu Ah Hong ◽  
Cheol Whee Park
Keyword(s):  
Antioxidant Enzymes ◽  
Reactive Nitrogen Species ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Lipid Peroxides ◽  
Hypertensive Nephropathy ◽  
Antioxidant Agents

Reactive oxygen species and reactive nitrogen species are highly implicated in kidney injuries that include acute kidney injury, chronic kidney disease, hypertensive nephropathy, and diabetic nephropathy. Therefore, antioxidant agents are promising therapeutic strategies for kidney diseases. Catalytic antioxidants are defined as small molecular mimics of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, and some of them function as potent detoxifiers of lipid peroxides and peroxynitrite. Several catalytic antioxidants have been demonstrated to be effective in a variety of in vitro and in vivo disease models that are associated with oxidative stress, including kidney diseases. This review summarizes the evidence for the role of antioxidant enzymes in kidney diseases, the classifications of catalytic antioxidants, and their current applications to kidney diseases.

Role of intracellular antioxidant enzymes after in vivo myocardial ischemia and reperfusion

2003 ◽  
Vol 284 (1) ◽  
pp. H277-H282 ◽  
Author(s):  
Steven P. Jones ◽  
Michaela R. Hoffmeyer ◽  
Brent R. Sharp ◽  
Ye-Shih Ho ◽  
David J. Lefer
Keyword(s):  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Myocardial Damage ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion

Reactive oxygen species induce myocardial damage after ischemia and reperfusion in experimental animal models. Numerous studies have investigated the deleterious effects of ischemia-reperfusion (I/R)-induced oxidant production using various pharmacological interventions. More recently, in vitro studies have incorporated gene-targeted mice to decipher the role of antioxidant enzymes in myocardial reperfusion injury. We examined the role of cellular antioxidant enzymes in the pathogenesis of myocardial I/R (MI/R) injury in vivo in gene-targeted mice. Neither deficiency nor overexpression of Cu-Zn superoxide dismutase (SOD) altered the extent of myocardial necrosis. Overexpression of glutathione peroxidase did not affect the degree of myocardial injury. Conversely, overexpression of manganese (Mn)SOD significantly attenuated myocardial necrosis after MI/R. Transthoracic echocardiography was performed on MnSOD-overexpressing and wild-type mice that were subjected to a more prolonged period of reperfusion. Cardiac output was significantly depressed in the nontransgenic but not the transgenic MnSOD-treated mice. Anterior wall motion was significantly impaired in the nontransgenic mice. These findings demonstrate an important role for MnSOD but not Cu/ZnSOD or glutathione peroxidase in mice after in vivo MI/R.

scholarly journals MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xudong Wang ◽  
Yali Wang ◽  
Mingjian Kong ◽  
Jianping Yang
Keyword(s):  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Periodic Acid ◽  
Kidney Injury ◽  
Luciferase Reporter ◽  
Tunel Staining ◽  
Tnf Α

Abstract Background: Septic acute kidney injury is considered as a severe and frequent complication that occurs during sepsis. The present study was performed to understand the role of miR-22-3p and its underlying mechanism in sepsis-induced acute kidney injury. Methods: Rats were injected with adenovirus carrying miR-22-3p or miR-NC in the caudal vein before cecal ligation. Meanwhile, HK-2 cells were transfected with the above adenovirus following LPS stimulation. We measured the markers of renal injury (blood urea nitrogen (BUN), serum creatinine (SCR)). Histological changes in kidney tissues were examined by hematoxylin and eosin (H&E), Masson staining, periodic acid Schiff staining and TUNEL staining. The levels of IL-1β, IL-6, TNF-α and NO were determined by ELISA assay. Using TargetScan prediction and luciferase reporter assay, we predicted and validated the association between PTEN and miR-22-3p. Results: Our data showed that miR-22-3p was significantly down-regulated in a rat model of sepsis-induced acute kidney injury, in vivo and LPS-induced sepsis model in HK-2 cells, in vitro. Overexpression of miR-22-3p remarkably suppressed the inflammatory response and apoptosis via down-regulating HMGB1, p-p65, TLR4 and pro-inflammatory factors (IL-1β, IL-6, TNF-α and NO), both in vivo and in vitro. Moreover, PTEN was identified as a target of miR-22-3p. Furthermore, PTEN knockdown augmented, while overexpression reversed the suppressive role of miR-22-3p in LPS-induced inflammatory response. Conclusions: Our results showed that miR-22-3p induced protective role in sepsis-induced acute kidney injury may rely on the repression of PTEN.

scholarly journals Antioxidant Therapy in Graves’ Orbitopathy

2020 ◽  
Vol 11 ◽  
Author(s):  
Giulia Lanzolla ◽  
Claudio Marcocci ◽  
Michele Marinò
Keyword(s):  
Ros Generation ◽  
Related Condition ◽  
Orbital Radiotherapy ◽  
Antioxidant Agents ◽  
Graves Orbitopathy ◽  
High Doses

The balance of the cell redox state is a key point for the maintenance of cellular homeostasis. Increased reactive oxygen species (ROS) generation leads to oxidative damage of tissues, which is involved in the development of several diseases, including autoimmune diseases. Graves’ Orbitopathy (GO) is a disfiguring autoimmune-related condition associated with Graves’ Disease (GD). Patients with active, moderate-to-severe GO, are generally treated with high doses intravenous glucocorticoids (ivGCs) and/or orbital radiotherapy. On the contrary, up to recently, local ointments were the treatment most frequently offered to patients with mild GO, because the risks related to ivGCs does not justify the relatively poor benefits expected in mild GO. However, a medical treatment for these patients is heavily wanted, considering that GO can progress into more severe forms and also patients with mild GO complain with an impairment in their quality of life. Thus, based on the role of oxidative stress in the pathogenesis of GO, a therapy with antioxidant agents has been proposed and a number of studies have been performed, both in vitro and in vivo, which is reviewed here.

scholarly journals The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity

2019 ◽  
Vol 20 (20) ◽  
pp. 5238 ◽  
Author(s):  
Daniela Maria Tanase ◽  
Evelina Maria Gosav ◽  
Smaranda Radu ◽  
Claudia Florida Costea ◽  
Manuela Ciocoiu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
In Vivo Studies ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Induced Apoptosis ◽  
Kidney Injury Molecule 1

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

scholarly journals Isoquercitrin Ameliorates Cisplatin-Induced Nephrotoxicity Via the Inhibition of Apoptosis, Inflammation, and Oxidative Stress

2020 ◽  
Vol 11 ◽  
Author(s):  
Hao Wang ◽  
Weiwei Xia ◽  
Guangfeng Long ◽  
Zhiyin Pei ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Cell Injury ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Epithelial Cell Line ◽  
Therapeutic Uses ◽  
And Oxidative Stress

Cisplatin is extensively used and is highly effective in clinical oncology; nevertheless, nephrotoxicity has severely limited its widespread utility. Isoquercitrin (IQC), a natural flavonoid widely found in herbage, is well known and recognized for its antioxidant, anti-inflammatory, and anti-apoptotic properties. However, the potential effects and mechanism of IQC in cisplatin-induced acute kidney diseases remain unknown. In this study, we postulated the potential effects and mechanism of IQC upon cisplatin exposure in vivo and in vitro. For the in vivo study, C57BL/6J mice were pretreated with IQC or saline (50 mg/kg/day) by gavage for 3 days before cisplatin single injection (25 mg/kg). Renal function, apoptosis, inflammation, oxidative stress and p-ERK were measured to evaluate kidney injury. In vitro, mouse proximal tubular cells (mPTCs) and human proximal tubule epithelial cell line (HK2) were pretreated with or without IQC (80 μM for mPTCs and 120 μM for HK2) for 2 h and then co-administrated with cisplatin for another 24 h. Apoptosis, inflammation, ROS and p-ERK of cells were also measured. In vivo, IQC administration strikingly reduced cisplatin-induced nephrotoxicity as evidenced by the improvement in renal function (serum creatinine and blood urea nitrogen), kidney histology (PAS staining), apoptotic molecules (cleaved caspase-3, caspase-8, Bax and Bcl-2), inflammatory cytokines (IL-1β, IL-6, TNF-α, and COX-2), oxidative stress (MDA and total glutathione) and p-ERK. In line with in vivo findings, IQC markedly protected against cisplatin-induced cell injury in mPTCs and HK2 cells. Collectively, these findings demonstrated that IQC administration could significantly protect against cisplatin nephrotoxicity possibly through ameliorating apoptosis, inflammation and oxidative stress accompanied by cross talk with p-ERK. Furthermore, IQC may have potential therapeutic uses in the treatment of cisplatin-induced acute kidney injury.

scholarly journals Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Qian Wang ◽  
Xuefei Tian ◽  
Wei’e Zhou ◽  
Yan Wang ◽  
Hailing Zhao ◽  
...  
Keyword(s):  
Renal Function ◽  
Transient Receptor Potential ◽  
Kidney Diseases ◽  
Protective Role ◽  
Protective Mechanism ◽  
Cell Matrix ◽  
Tangshen Formula

Tangshen Formula (TSF) is a Chinese Medicine formula that has been reported to alleviate proteinuria and protect renal function in humans and animals with diabetic kidney disease (DKD). However, little is known about its mechanism in improving proteinuria. The dysregulation of podocyte cell-matrix adhesion has been demonstrated to play an important role in the pathogenesis and progression of proteinuric kidney diseases including DKD. In the present study, the underlying protective mechanism of TSF on podocytes was investigated using the murine model of type 2 DKD db/db mice in vivo and advanced glycation end products (AGEs)-stimulated primary mice podocytes in vitro. Results revealed that TSF treatment could significantly mitigate reduction of podocyte numbers and foot process effacement, reduce proteinuria, and protect renal function in db/db mice. There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice. The results of AGEs-stimulated primary mice podocytes showed increased cell migration and actin-cytoskeleton rearrangement. Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca2+ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2. These dysregulations in mice primary podocytes stimulated by AGEs could be significantly attenuated after TSF treatment. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a TRPC6 agonist, blocked the protective role of TSF on podocyte cell-matrix adherence. In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.

scholarly journals ING2 Controls Mitochondrial Respiration via Modulating MRPL12 Ubiquitination in Renal Tubular Epithelial Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Ying Yang ◽  
Chensheng Li ◽  
Xia Gu ◽  
Junhui Zhen ◽  
Suwei Zhu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mitochondrial Respiration ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Mitochondrial Injury ◽  
Mitochondrial Transcription Factor ◽  
Mtdna Transcription

Mitochondrial injury of tubular epithelial cells (TECs) is the key pathogenic event underlying various kidney diseases and a potential intervening target as well. Our previous study demonstrated that ING2 is ubiquitously expressed at tubulointerstitial area within kidneys, while its role in regulating TEC mitochondrial respiration is not fully elucidated. To clarify the roles of ING2 in mitochondrial homeostasis of TECs and pathogenesis of acute ischemic kidney injury, Western blot, PCR, immunofluorescence, immunoprecipitation, and oxygen consumption rate assay were applied to address the roles of ING2 in modulating mitochondrial respiration. We further complemented these studies with acute ischemic kidney injury both in vitro and in vivo. In vitro study demonstrated ING2 could positively control TEC mitochondrial respiration. Concurrently, both mRNA and protein levels of mtDNA encoded respiratory chain components were altered by ING2, suggesting ING2 could regulate mtDNA transcription. In mechanism, ING2 could regulate the ubiquitination of a newly identified mitochondrial transcription factor MRPL12, thereby modulating its cellular stability and abundance. We also demonstrated ING2-mediated modulation on mtDNA transcription and mitochondrial respiration are involved in serum deprivation induced TEC injuries. Finally, immunohistochemistry study revealed that ING2 expression was significantly altered in kidney biopsies with acute ischemic kidney injury. In vivo study suggested that kidney specific ING2 overexpression could effectively ameliorate acute ischemic kidney injury. Our study demonstrated that ING2 is a crucial modulator of TEC mitochondrial respiration. These findings suggested a unrecognized role of ING2 in TEC mitochondrial energetic homeostasis and a potential intervening target for TEC mitochondrial injury associated pathologies.

scholarly journals Role of TRPA1 in Tissue Damage and Kidney Disease

2021 ◽  
Vol 22 (7) ◽  
pp. 3415
Author(s):  
Chung-Kuan Wu ◽  
Ji-Fan Lin ◽  
Tzong-Shyuan Lee ◽  
Yu Ru Kou ◽  
Der-Cherng Tarng
Keyword(s):  
Kidney Disease ◽  
Tissue Damage ◽  
Animal Studies ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Cell Types ◽  
Renal Tubular

TRPA1, a nonselective cation channel, is expressed in sensory afferent that innervates peripheral targets. Neuronal TRPA1 can promote tissue repair, remove harmful stimuli and induce protective responses via the release of neuropeptides after the activation of the channel by chemical, exogenous, or endogenous irritants in the injured tissue. However, chronic inflammation after repeated noxious stimuli may result in the development of several diseases. In addition to sensory neurons, TRPA1, activated by inflammatory agents from some non-neuronal cells in the injured area or disease, might promote or protect disease progression. Therefore, TRPA1 works as a molecular sentinel of tissue damage or as an inflammation gatekeeper. Most kidney damage cases are associated with inflammation. In this review, we summarised the role of TRPA1 in neurogenic or non-neurogenic inflammation and in kidney disease, especially the non-neuronal TRPA1. In in vivo animal studies, TRPA1 prevented sepsis-induced or Ang-II-induced and ischemia-reperfusion renal injury by maintaining mitochondrial haemostasis or via the downregulation of macrophage-mediated inflammation, respectively. Renal tubular epithelial TRPA1 acts as an oxidative stress sensor to mediate hypoxia–reoxygenation injury in vitro and ischaemia–reperfusion-induced kidney injury in vivo through MAPKs/NF-kB signalling. Acute kidney injury (AKI) patients with high renal tubular TRPA1 expression had low complete renal function recovery. In renal disease, TPRA1 plays different roles in different cell types accordingly. These findings depict the important role of TRPA1 and warrant further investigation.

scholarly journals Cisplatin induces acute kidney injury and pyroptosis in mice through the exosome miR-122/ELAVL1 regulatory axis

2020 ◽  
Author(s):  
Bei Zhu ◽  
Xiaoshuang Ye ◽  
Fei Gao ◽  
Yun Bai ◽  
Zhouyi Chan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Regulation Mechanism ◽  
Substrate Protein ◽  
Functional Components ◽  
Hk2 Cells

Abstract Background Although cisplatin is an effective chemotherapeutic drug for the treatment of various cancers, its clinical application is limited due to its side effects, especially nephrotoxicity. Unfortunately, Acute kidney injury (AKI) caused by cisplatin remains one of the main obstacles to cancer treatment. Increasing evidence suggests that renal inflammation and pyroptotic inflammatory cell death of tubular epithelial cells (RTECs) mainly determine the progression and outcome of cisplatin-induced AKI. However, it is not clear how cisplatin regulates the pyroptosis of RTECs cells in AKI. The current study aimed to determine the regulation mechanism of AKI induced by cisplatin. In vivo, cisplatin was used to induce AKI. H&E staining of mouse kidney tissue sections and serological indicators of kidney injury (including BUN, serum creatinine and TNF-α) were detected. The important substrate protein GSDMD and key target caspase-1 of pyroptosis were detected by immunohistochemistry and western blot, respectively. In vitro, cisplatin significantly induces HK-2 cells pyroptosis. Furthermore, Cisplatin transmits HK2 cells pyroptosis signals to surrounding cells in the form of exosomes. Previous studies have shown that exosomes are involved in kidney physiology and the pathogenesis of various kidney diseases/disorders. MicroRNAs (miRNAs) are the main functional components of exosomes. Results Further research shows that exosome miR-122 negatively regulates the pyrolysis of HK2 cells. Finally, we elucidated that exosome miR-122 participates in cisplatin induced AKI regulation by regulating ELAVL1 expression. Conclusions In conclusion, these results suggest that exosome miR-122 inhibits pyroptosis and AKI by targeting ELAVL1 under cisplatin treatment, which will provide a potential target for the treatment of AKI.

scholarly journals Regulatory B Cell Therapy in Kidney Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Sergio G. Garcia ◽  
Noelia Sandoval-Hellín ◽  
Marcella Franquesa
Keyword(s):  
Kidney Transplantation ◽  
Cell Therapy ◽  
Cell Subset ◽  
Kidney Injury ◽  
Specific Marker ◽  
Regulatory B Cell ◽  
Unique Cell

In the context of kidney injury, the role of Bregs is gaining interest. In a number of autoimmune diseases, the number and/or the function of Bregs has been shown to be impaired or downregulated, therefore restoring their balance might be a potential therapeutic tool. Moreover, in the context of kidney transplantation their upregulation has been linked to tolerance. However, a specific marker or set of markers that define Bregs as a unique cell subset has not been found and otherwise multiple phenotypes of Bregs have been studied. A quest on the proper markers and induction mechanisms is now the goal of many researchers. Here we summarize the most recent evidence on the role of Bregs in kidney disease by describing the relevance of in vitro and in vivo Bregs induction as well as the potential use of Bregs as cell therapy agents in kidney transplantation.

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