scholarly journals Comparative Study of Protective Action of Exogenous 2-Cys Peroxiredoxins (Prx1 and Prx2) Under Renal Ischemia-Reperfusion Injury

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 680
Author(s):  
Mars G. Sharapov ◽  
Ruslan G. Goncharov ◽  
Gleb I. Filkov ◽  
Alexander V. Trofimenko ◽  
Valery V. Boyarintsev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Action ◽  
Free Radical Oxidation ◽  
Biological Macromolecules ◽  
Secondary Products ◽  
Radical Oxidation ◽  
Wide Range

The pathogenesis of ischemia-reperfusion (I/R) injuries is based on oxidative stress caused by a sharp increase in the concentration of free radicals, reactive oxygen species (ROS) and secondary products of free radical oxidation of biological macromolecules during reperfusion. Application of exogenous antioxidants lowers the level of ROS in the affected tissues, suppresses or adjusts the course of oxidative stress, thereby substantially reducing the severity of I/R injury. We believe that the use of antioxidant enzymes may be the most promising line of effort since they possess higher efficiency than low molecular weight antioxidants. Among antioxidant enzymes, of great interest are peroxiredoxins (Prx1–6) which reduce a wide range of organic and inorganic peroxide substrates. In an animal model of bilateral I/R injury of kidneys (using histological, biochemical, and molecular biological methods) it was shown that intravenous administration of recombinant typical 2-Cys peroxiredoxins (Prx1 and Prx2) effectively reduces the severity of I/R damage, contributing to the normalization of the structural and functional state of the kidneys and an almost 2-fold increase in the survival of experimental animals. The use of recombinant Prx1 or Prx2 can be an efficient approach for the prevention and treatment of renal I/R injury.

Abstract MP58: Tissue And Sex Specific Effects Of Gstm1 Deletion In Mouse Models

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yves Wang ◽  
Nhu Nguyen ◽  
Keith Nehrke ◽  
Paul S Brookes ◽  
Thu H Le
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Iri Model ◽  
Increased Risk ◽  
Study Gene Expression

The glutathione S-transferase ( Gst ) gene family encodes antioxidant enzymes. In humans, a common null allele deletion variant of GST μ-1 ( GSTM1 ) is highly prevalent across populations and is associated with increased risk and progression of various diseases. Using a Gstm1 knockout (KO) mouse model, we previously showed that KO mice with angiotensin II-induced hypertension (HTN) have increased kidney injury compared to wild-type (WT) controls, mediated by elevated oxidative stress. In the same mouse model, we have recently reported that in a Langendorff-perfused cardiac ischemia-reperfusion injury (IRI) model, where damage is also mediated by oxidative stress, male KO hearts are protected while females are not. Here, we investigated the molecular mechanisms for this difference in male hearts. WT and KO mice of both sexes were studied at 12-20 weeks of age. Hearts were snap frozen at baseline and after 25 min of global ischemia, and kidneys were collected at baseline and 4 weeks following HTN induction. A panel of 18 Gst genes were probed by qPCR from baseline hearts and kidneys of both sexes. Global metabolites were assayed using Metabolon, Inc. from hearts of both sexes and kidneys of males, at both baseline and diseased states. Analysis by qPCR (n = 3/group) showed that male, but not female, KO hearts had upregulation of other Gst s. In contrast, no significant differences between were found in male kidneys. Metabolomics (n = 6/group) detected 695 metabolites in hearts and 926 in kidneys. There were increases in several metabolites in KO vs. WT hearts including those with antioxidant properties. Notably, increases in carnosine and anserine were observed in KO male hearts but not in female hearts, while that of other antioxidant-related metabolites were observed in hearts of both sexes, but not in kidneys. HTN induced significant increases in metabolites in KO vs. WT kidneys in the pathways related to and linking methionine, cysteine, and glutathione, which were not observed in hearts. In this study, gene expression and metabolites suggest that the mechanisms compensating for the loss of GSTM1 are both tissue and sex specific. The resulting differences in antioxidant enzymes and metabolites may explain the unexpected protection for male Gstm1 KO hearts in IRI.

scholarly journals Cabbage (Brassica oleracea var. capitata) Protects against H2O2-Induced Oxidative Stress by Preventing Mitochondrial Dysfunction in H9c2 Cardiomyoblasts

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Dong Kwon Yang
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Ros Production ◽  
Hepatic Diseases ◽  
Mitochondrial Functions ◽  
Wide Range ◽  
H9c2 Cardiomyoblasts ◽  
Cabbage Extract

Oxidative stress plays an important role in the progression of cardiac diseases, including ischemia/reperfusion injury, myocardial infarction, and heart failure. Growing evidence indicates that cabbage has various pharmacological properties against a wide range of diseases, such as cardiovascular diseases, hepatic diseases, and cancer. However, little is known about its effects on oxidative stress in cardiomyocytes or the underlying mechanisms. Therefore, the present study examined the effects of cabbage extract on oxidative stress in H9c2 cardiomyoblasts. Cell viability, reactive oxygen species (ROS) production, apoptosis, mitochondrial functions, and expression levels of mitogen-activated protein kinase (MAPK) proteins were analyzed to elucidate the antioxidant effects of this extract. Cabbage extract protected against H2O2-induced cell death and did not elicit any cytotoxic effects. In addition, cabbage extract suppressed ROS production and increased expression of antioxidant proteins (SOD-1, catalase, and GPx). Cabbage extract also inhibited apoptotic responses and activation of MAPK proteins (ERK1/2, JNK, and p-38) in oxidative stress-exposed H9c2 cells. Notably, cabbage extract preserved mitochondrial functions upon oxidative stress. These findings reveal that cabbage extract protects against oxidative stress and suggest that it can be used as an alternative therapeutic strategy to prevent the oxidative stress in the heart.

scholarly journals Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury through inhibiting alveolar macrophages pyroptosis via Keap1/Nrf-2/HO-1 signal pathway

2020 ◽  
Author(s):  
Lin Fei ◽  
Xiao Jingyuan ◽  
Liang Fangte ◽  
Dai Huijun ◽  
Ye Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Lung Injury ◽  
Reperfusion Injury ◽  
Lung Tissue ◽  
Alveolar Macrophages ◽  
Tissue Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lung Tissue Damage

Abstract Background Lung ischemia-reperfusion injury (LIRI) is a common and complex pathophysiological process that can lead to poor patient outcomes. Inflammasome-dependent macrophage pyroptosis contributes to organ damage caused by ischemia-reperfusion (I/R). Oxidative stress reaction and antioxidant enzymes also play an important role in LIRI. This experiment was conducted to investigate whether preconditioning with rHMGB1 could ameliorate LIRI and explore the mechanisms of its protective effect in a lung I/R mice model. Methods Adult male mice were anesthetized and the left hilus pulmonis was clamped for 60 min, followed by 120 min of reperfusion. rHMGB1 was performed by intraperitoneal injection at 2 h before anesthesia. Brusatol (Nrf-2 antagonist) was given intraperitoneally every other day for a total of five times before surgery. Measurements of pathohistological lung tissue damage, pulmonary wet/dry (W/D) ratios, inflammatory mediators were performed to assess the extent of lung injury after I/R. Alveolar macrophages (AMs) pyroptosis were evaluated by LDH release, caspase-1 expression in flow cytometry, GSDMD expression in immunofluorescent staining. Measurement of the products of oxidative Stress (ROS, MDA, 15-F2t-Isoprostane) and the antioxidant enzymes (SOD, GSH-PX, CAT) were performed. Results Preconditioning with rHMGB1 significantly ameliorated I/R-induced lung injury through measuring the morphology, wet/dry weight ratio, the expressions of IL-1β, IL-6, NF-κB, HMGB1 in lung tissue. rHMGB1 preconditioning remarkably alleviated AMs pyroptosis induced by lung I/R. rHMGB1 preconditioning significantly reduced oxidative stress and restored the activity of antioxidative enzymes. In addition, rHMGB1 preconditioning mediated the activity of Keap1/Nrf-2/HO-1 pathway in LIRI. Furthermore, inhibiting Keap1/Nrf-2/HO-1 pathway through brusatol administration could aggravate lung tissue damage and inflammatory response after lung I/R. Also, brusatol administration could suppresse the antioxidant and anti-pyroptosis effects of rHMGB1 preconditioning in LIRI. Conclusions rHMGB1 preconditioning protects against LIRI through suppressing AMs pyroptosis. The mechanism is partially explained by inhibiting oxidative stress and improving the activity of antioxidative enzymes via Keap1/Nrf-2/HO-1 pathway.

scholarly journals Astragaloside IV Attenuates Myocardial Ischemia-Reperfusion Injury from Oxidative Stress by Regulating Succinate, Lysophospholipid Metabolism, and ROS Scavenging System

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Miaomiao Jiang ◽  
Jingyu Ni ◽  
Yuanlin Cao ◽  
Xiaoxue Xing ◽  
Qian Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Ros Scavenging ◽  
Astragaloside Iv ◽  
Wide Range

Astragaloside IV is one of the main active ingredients isolated from Astragalus membranaceus. Here we confirmed its protective effect against cardiac ischemia-reperfusion (I/R) injury and aimed to investigate the potential molecular mechanisms involved. Pretreatment of ex vivo and in vivo I/R-induced rat models by astragaloside IV significantly prevented the ratio of myocardium infarct size, systolic and diastolic dysfunction, and the production of creatine kinase and lactate dehydrogenase. Metabolic analyses showed that I/R injury caused a notable reduction of succinate and elevation of lysophospholipids, indicating excessive reactive oxygen species (ROS) generation driven by succinate’s rapid reoxidization and glycerophospholipid degradation. Molecular validation mechanistically revealed that astragaloside IV stimulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) released from Kelch-like ECH-associated protein 1 (Keap1) and translocated to the nucleus to combine with musculoaponeurotic fibrosarcoma (Maf) to initiate the transcription of antioxidative gene heme oxygenase-1 (HO-1), which performed a wide range of ROS scavenging processes against pathological oxidative stress in the hearts. As expected, increasing succinate and decreasing lysophospholipid levels were observed in the astragaloside IV-pretreated group compared with the I/R model group. These results suggested that astragaloside IV ameliorated myocardial I/R injury by modulating succinate and lysophospholipid metabolism and scavenging ROS via the Nrf2 signal pathway.

scholarly journals Preconditioning with rHMGB1 ameliorates lung ischemia–reperfusion injury through inhibiting alveolar macrophages pyroptosis via Keap1/Nrf2/HO-1 signal pathway

2020 ◽  
Author(s):  
Lin Fei ◽  
Xiao Jingyuan ◽  
Liang Fangte ◽  
Dai Huijun ◽  
Ye Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Lung Injury ◽  
Reperfusion Injury ◽  
Lung Tissue ◽  
Alveolar Macrophages ◽  
Tissue Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lung Tissue Damage

Abstract Background: Lung ischemia-reperfusion injury (LIRI) is a common and complex pathophysiological process that can lead to poor patient outcomes. Inflammasome-dependent macrophage pyroptosis contributes to organ damage caused by ischemia-reperfusion (I/R). Oxidative stress reaction and antioxidant enzymes also play an important role in LIRI. This experiment was conducted to investigate whether preconditioning with rHMGB1 could ameliorate LIRI and explore the mechanisms of its protective effect in a lung I/R mice model. Methods: Adult male mice were anesthetized and the left hilus pulmonis was clamped for 60 min, followed by 120 min of reperfusion. rHMGB1 was performed by intraperitoneal injection at 2 h before anesthesia. Brusatol (Nrf2 antagonist) was given intraperitoneally every other day for a total of five times before surgery. Measurements of pathohistological lung tissue damage, pulmonary wet/dry (W/D) ratios and inflammatory mediators were performed to assess the extent of lung injury after I/R. Alveolar macrophages (AMs) pyroptosis were evaluated by LDH release, caspase-1 expression in flow cytometry, GSDMD expression in immunofluorescent staining. The products of oxidative Stress (ROS, MDA, 15-F2t-Isoprostane) and the antioxidant enzymes (SOD, GSH-PX, CAT) were detected.Results: Preconditioning with rHMGB1 significantly ameliorated I/R-induced lung injury through measuring the morphology, wet/dry weight ratio, the expressions of IL-1β, IL-6, NF-κB and HMGB1 in lung tissue. rHMGB1 preconditioning remarkably alleviated AMs pyroptosis induced by lung I/R. rHMGB1 preconditioning significantly reduced oxidative stress and restored the activity of antioxidative enzymes. In addition, rHMGB1 preconditioning mediated the activity of Keap1/Nrf2/HO-1 pathway in LIRI. Furthermore, inhibiting Keap1/Nrf2/HO-1 pathway through brusatol administration could aggravate lung tissue damage and inflammatory response after lung I/R. And these effects by brusatol administration could be alleviated by rHMGB1 preconditioning in LIRI .Conclusions : rHMGB1 preconditioning protects against LIRI through suppressing AMs pyroptosis. The molecular mechanism could be partially explained by inhibiting oxidative stress and improving the activity of antioxidative enzymes via Keap1/Nrf2/HO-1 pathway upon rHMGB1 preconditioning.

State of the enzyme link of antioxidant protection in boys with hypoandrogenism

2020 ◽  
Vol 40 (4) ◽  
pp. 32-36
Author(s):  
L. K. Parkhomenko ◽  
◽  
L. A. Strashok ◽  
S. I. Turchina ◽  
G. V. Kosovtsova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Free Radical ◽  
Glutathione Peroxidase ◽  
Free Radical Oxidation ◽  
Conjugated Dienes ◽  
Delayed Puberty ◽  
Control Group ◽  
Antioxidant Protection ◽  
Radical Oxidation

Recently, interest in the problem of free radical oxidation in biological membranes, which is directly related to both the normal functioning of cells and the occurrence, course and outcome of many pathological conditions, has increased again in clinical medicine. The aim was to determine the role and impact of antioxidant defense in boys with hypoandrogenism. The study involved 75 adolescents with hypoandrogenism aged 13–18 years, who underwent a complex of clinical and laboratory examinations. All patients were conducted complex of anthropometric research and determination of the degree of delayed puberty, laboratory and instrumental examination. Free radical oxidation was determined by the levels of malondialdehyde, conjugated dienes, carbonated proteins, superoxide dismutase and catalase in the serum, and restored glutathione and glutathione peroxidase in whole blood. Based on their determination, the coefficient of oxidative stress was calculated. Statistical processing of results was performed using parametric and nonparametric methods. The study of indicators of the free radical oxidation process found that adolescents with hypoandrogenism have multidirectional changes in the oxidation of proteins and lipids, namely: the level of conjugated dienes increases, the concentration of malondialdehyde remains at the level of the control group, and the level of carbonated proteins tends to decrease. As for the activity of antioxidant protection enzymes, a significant decrease in the level of glutathione peroxidase was detected, while the level of superoxide dismutase and catalase remained at the level of normative indicators. Oxidative stress accompanies and is one of the pathogenetic links in the formation or maintenance of the state of hypoandrogenism in boys. This requires the use of antioxidants, the complex of which must be selected individually.

Gender differences in biochemical measurement reflecting the state of free-radical oxidation and antioxidant protection among workers in metallurgical production

2019 ◽  
Vol 1 (10) ◽  
pp. 877-881
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Gender Differences ◽  
Free Radical ◽  
Biochemical Parameters ◽  
Free Radical Oxidation ◽  
The Body ◽  
Antioxidant Protection ◽  
Radical Oxidation ◽  
Metallurgical Production ◽  
Production Factors

Introduction. To date, age and sex differences have been established for many biochemical parameters. Gender differences in indicators for systems such as antioxidant, thiol-disulfide, oxidative stress and inflammation systems are absent or under study.The aim of the study was to identify gender differences in biochemical parameters reflecting the functioning of antioxidant systems of the body and free radical oxidation in workers of metallurgical production, in contact with harmful production factors.Materials and methods. The blood of men and women working at the metallurgical enterprise of the Nizhny Novgorod region (n=80) under the influence of a complex of physical and chemical production factors was studied. Total oxidative stress, total antioxidant capacity of serum, glutathione levels were studied by photometric biochemical methods. Levels of C-reactive protein and 8-hydroxy–2-deoxyguanosine were studied by ELISA.Results. The average amount of peroxides in the serum of women exceeded 1.6 times this figure in men. In the group of men, the content of 8-Ondg was higher by 26% (p=0.012), the level of GS-by 12% (p=0.019), the activity of SOD — by 1.5–2 times (p=0.0001), the level of CRP — by 2 times (p=0.008) compared to similar indicators in women.Conclusions. Studies of gender differences in workers under the influence of harmful production factors will allow more effective approach to the etiology, treatment and prognosis of production-related diseases. Indicators of oxidative stress and antioxidant protection can be indicators of the health of workers under the influence of harmful industrial factors and be important in the prevention of diseases associated with oxidative stress.

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 microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

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