Herbal antioxidants and renal ischemic-reperfusion injury; an updated review

Renal ischemia-reperfusion (RIR) is a pathological condition due to transient restriction of blood flow to the kidneys, which is followed by the subsequent recovery of perfusion and re-oxygenation. RIR injury contributes to the progression of renal dysfunction including acute kidney injury (AKI) in native and renal allograft transplant. The generation of reactive oxygen species (ROS) during oxidative stress contributes to the occurrence of RIR. Hence, the use of antioxidant compounds can improve oxidative stress due to RIR. This review highlights herbal antioxidant efficacy against RIR injury. The findings of this study indicate that antioxidant compounds with herbal origin could reduce complications due to oxidative stress related to RIR through diminishing lipid peroxidation, decreased production of malondialdehyde (MDA), apoptosis and increasing antioxidant enzymes activity. Reducing oxidative stress with the pharmacological approach of antioxidants can be a desirable target for ameliorating RIR.

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Danshensu Rescues Ischemia/Reperfusion Caused Human Hepatocyte Death

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.17:117-121 ◽

2018 ◽

Vol 17 (2) ◽

pp. 117-121

Author(s):

Sun Maw-Sheng ◽

Liang Chun-Ya ◽

Hsieh Po-Chun ◽

Kuo Chan-Yen

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Caspase 3 ◽

Ischemia Reperfusion ◽

Oxygen Species ◽

Good Strategy ◽

Ros Accumulation ◽

Dichlorofluorescin Diacetate ◽

Hepatocyte Damage ◽

Hepatocyte Death

Apoptosis of hepatocyte, under ischemia/reperfusion (IR) conditions, has been identified as an essential process in the progression of liver transplantation. Under these conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). Additionally, ROS overproduction may induce inflammation. As ROS accumulation appears to cause hepatocyte damage or death, there has been considerable interest in identifying the candidate natural products involved and in developing strategies to reduce oxidative stress. In this study, we use Danshensu as a candidate product to speculate whether has the protective effect on apoptotic hepatocyte upon IR. To speculate the apoptotic phenomena was reversed by Danshensu, we detected the p53, cleaved-caspase 3 expression by western blotting, as well as caspase-3 activity. Additionally, we analyzed the ROS levels by 2′,7′-dichlorofluorescin diacetate (DCF-DA) staining. We also detected the cell viability by WST-1. Results showed that Danshensu alleviated hypoxia-caused cell apoptosis via ROS overproduction. We suggested that Danshensu is a good strategy for treating hepatocyte damage upon IR.

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Magnesium deficiency augments myocardial response to reactive oxygen species

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y06-017 ◽

2006 ◽

Vol 84 (6) ◽

pp. 617-624 ◽

Cited By ~ 5

Author(s):

L. Manju ◽

R. Renuka Nair

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Lipid Peroxidation ◽

Tissue Injury ◽

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Oxygen Species ◽

Inotropic Response ◽

Mg Deficiency ◽

Negative Inotropic Response

Magnesium (Mg) deficiency and oxidative stress are independently implicated in the etiopathogenesis of various cardiovascular disorders. This study was undertaken to examine the hypothesis that Mg deficiency augments the myocardial response to oxidative stress. Electrically stimulated rat papillary muscle was used for recording the contractile variation. Biochemical variables of energy metabolism (adenosine triphosphate (ATP) and creatine phosphate) and markers of tissue injury (lactate dehydrogenase (LDH) release and lipidperoxidation), which can affect myocardial contractility, were assayed in Langendorff-perfused rat hearts. Hydrogen peroxide (100 µmol/L) was used as the source of reactive oxygen species. The negative inotropic response to H2O2 was significantly higher in Mg deficiency (0.48 mmol Mg/L) than in Mg sufficiency (1.2 mmol Mg/L). Low Mg levels did not affect ATP levels or tissue lipid peroxidation. However, H2O2 induced a decrease in ATP; enhanced lipid peroxidation and the release of LDH were augmented by Mg deficiency. Increased lipid peroxidation associated with a decrease in available energy might be responsible for the augmentation of the negative inotropic response to H2O2 in Mg deficiency. The observations from this study validate the hypothesis that myocardial response to oxidative stress is augmented by Mg deficiency. This observation has significance in ischemia–reperfusion injury, where Mg deficiency can have an additive effect on the debilitating consequences.

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SARS-CoV-2 and Other Respiratory Viruses: What Does Oxidative Stress Have to Do with It?

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/8844280 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Iara Grigoletto Fernandes ◽

Cyro Alves de Brito ◽

Vitor Manoel Silva dos Reis ◽

Maria Notomi Sato ◽

Nátalli Zanete Pereira

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Severe Acute Respiratory Syndrome ◽

Viral Infections ◽

Reactive Oxygen ◽

Antioxidant Compounds ◽

Oxygen Species ◽

Antiviral Therapies ◽

Species Production ◽

Relationship Of

The phenomenon of oxidative stress, characterized as an imbalance in the production of reactive oxygen species and antioxidant responses, is a well-known inflammatory mechanism and constitutes an important cellular process. The relationship of viral infections, reactive species production, oxidative stress, and the antiviral response is relevant. Therefore, the aim of this review is to report studies showing how reactive oxygen species may positively or negatively affect the pathophysiology of viral infection. We focus on known respiratory viral infections, especially severe acute respiratory syndrome coronaviruses (SARS-CoVs), in an attempt to provide important information on the challenges posed by the current COVID-19 pandemic. Because antiviral therapies for severe acute respiratory syndrome coronaviruses (e.g., SARS-CoV-2) are rare, knowledge about relevant antioxidant compounds and oxidative pathways may be important for understanding viral pathogenesis and identifying possible therapeutic targets.

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Modulatory Effect of Myokines on Reactive Oxygen Species in Ischemia/Reperfusion

International Journal of Molecular Sciences ◽

10.3390/ijms21249382 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9382

Author(s):

Márton Richárd Szabó ◽

Márton Pipicz ◽

Tamás Csont ◽

Csaba Csonka

Keyword(s):

Oxidative Stress ◽

Physical Activity ◽

Reactive Oxygen Species ◽

Skeletal Muscle ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Oxygen Species ◽

Interleukin 7 ◽

Species Formation

There is a growing body of evidence showing the importance of physical activity against acute ischemic events in various organs. Ischemia/reperfusion injury (I/R) is characterized by tissue damage as a result of restriction and subsequent restoration of blood supply to an organ. Oxidative stress due to increased reactive oxygen species formation and/or insufficient antioxidant defense is considered to play an important role in I/R. Physical activity not only decreases the general risk factors for ischemia but also confers direct anti-ischemic protection via myokine production. Myokines are skeletal muscle-derived cytokines, representing multifunctional communication channels between the contracting skeletal muscle and other organs through an endocrine manner. In this review, we discuss the most prominent members of the myokines (i.e., brain-derived neurotrophic factor (BDNF), cathepsin B, decorin, fibroblast growth factors-2 and -21, follistatin, follistatin-like, insulin-like growth factor-1; interleukin-6, interleukin-7, interleukin-15, irisin, leukemia inhibitory factor, meteorin-like, myonectin, musclin, myostatin, and osteoglycin) with a particular interest in their potential influence on reactive oxygen and nitrogen species formation or antioxidant capacity. A better understanding of the mechanism of action of myokines and particularly their participation in the regulation of oxidative stress may widen their possible therapeutic use and, thereby, may support the fight against I/R.

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Intermittent Hypoxia Prevents Myocardial Mitochondrial Ca2+ Overload and Cell Death during Ischemia/Reperfusion: The Role of Reactive Oxygen Species

Cells ◽

10.3390/cells8060564 ◽

2019 ◽

Vol 8 (6) ◽

pp. 564 ◽

Cited By ~ 7

Author(s):

Jui-Chih Chang ◽

Chih-Feng Lien ◽

Wen-Sen Lee ◽

Huai-Ren Chang ◽

Yu-Cheng Hsu ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Cell Death ◽

Antioxidant Enzymes ◽

Membrane Potential ◽

Antioxidant Capacity ◽

Intermittent Hypoxia ◽

Mitochondrial Membrane ◽

Ischemia Reperfusion ◽

Oxygen Species

It has been documented that reactive oxygen species (ROS) contribute to oxidative stress, leading to diseases such as ischemic heart disease. Recently, increasing evidence has indicated that short-term intermittent hypoxia (IH), similar to ischemia preconditioning, could yield cardioprotection. However, the underlying mechanism for the IH-induced cardioprotective effect remains unclear. The aim of this study was to determine whether IH exposure can enhance antioxidant capacity, which contributes to cardioprotection against oxidative stress and ischemia/reperfusion (I/R) injury in cardiomyocytes. Primary rat neonatal cardiomyocytes were cultured in IH condition with an oscillating O2 concentration between 20% and 5% every 30 min. An MTT assay was conducted to examine the cell viability. Annexin V-FITC and SYTOX green fluorescent intensity and caspase 3 activity were detected to analyze the cell death. Fluorescent images for DCFDA, Fura-2, Rhod-2, and TMRM were acquired to analyze the ROS, cytosol Ca2+, mitochondrial Ca2+, and mitochondrial membrane potential, respectively. RT-PCR, immunocytofluorescence staining, and antioxidant activity assay were conducted to detect the expression of antioxidant enzymes. Our results show that IH induced slight increases of O2−· and protected cardiomyocytes against H2O2- and I/R-induced cell death. Moreover, H2O2-induced Ca2+ imbalance and mitochondrial membrane depolarization were attenuated by IH, which also reduced the I/R-induced Ca2+ overload. Furthermore, treatment with IH increased the expression of Cu/Zn SOD and Mn SOD, the total antioxidant capacity, and the activity of catalase. Blockade of the IH-increased ROS production abolished the protective effects of IH on the Ca2+ homeostasis and antioxidant defense capacity. Taken together, our findings suggest that IH protected the cardiomyocytes against H2O2- and I/R-induced oxidative stress and cell death through maintaining Ca2+ homeostasis as well as the mitochondrial membrane potential, and upregulation of antioxidant enzymes.

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Intracellular Reactive Oxygen Species Mediate the Therapeutic Effect of Induced Pluripotent Stem Cells for Acute Kidney Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1609638 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Shun Wang ◽

Xiaoyu Tian ◽

Yijun Li ◽

Rong Xue ◽

Haochen Guan ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Acute Kidney Injury ◽

Therapeutic Effect ◽

Pluripotent Stem Cells ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Oxygen Species ◽

Renal Ischemia Reperfusion Injury ◽

Induced Pluripotent

Aims. Treatment for acute kidney injury (AKI) is challenging. Induced pluripotent stem cells (iPSCs) have great therapeutic potential. This study sought to determine whether iPSCs attenuate AKI and the role of reactive oxygen species (ROS). Results. We intravenously injected isogenic iPSCs into mice 2 h after renal ischemia-reperfusion injury (IRI). The cells were selectively trafficked to ischemia/reperfusion-injured kidney where they decreased kidney ROS and inflammatory cytokines and improved kidney function and morphology. Pretreating the cells with ROS inhibitors before administration decreased iPSC engraftment and abolished the protective effect of iPSCs. In contrast, pretreating iPSCs with hydrogen peroxide increased iPSC engraftment and therapeutic effect. Although the intravenously administered iPSCs trafficked to the IRI kidney, the cells did not differentiate into proximal or distal tubular epithelial cells. In vitro, the capabilities of the iPSC-released substances to promote proliferation and decrease apoptosis of renal epithelial cells were increased by ROS pretreatment of iPSCs. Moreover, pretreatment of the iPSCs with ROS inhibitor had the opposite effect. Similarly, moderate concentrations of ROS increased while ROS inhibitors decreased iPSC mobility, adhesion to the extracellular matrix, and mitochondrial metabolism. Innovation and Conclusion. iPSCs decreased renal ischemia/reperfusion injury mainly through iPSC-released substances. The therapeutic effect, mitochondrial metabolism, mobility, and kidney trafficking of iPSCs were ROS dependent.

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Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia

International Journal of Molecular Sciences ◽

10.3390/ijms22041729 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1729

Author(s):

Yun Liu ◽

Mengxue Wang ◽

Yin Liang ◽

Chen Wang ◽

Keiji Naruse ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Infarction ◽

Reactive Oxygen Species ◽

Ischemia Reperfusion ◽

Ros Generation ◽

Oxygen Species ◽

New Findings ◽

Important Intermediate ◽

Endogenous Antioxidants ◽

Material Exchange

A thrombus in a coronary artery causes ischemia, which eventually leads to myocardial infarction (MI) if not removed. However, removal generates reactive oxygen species (ROS), which causes ischemia–reperfusion (I/R) injury that damages the tissue and exacerbates the resulting MI. The mechanism of I/R injury is currently extensively understood. However, supplementation of exogenous antioxidants is ineffective against oxidative stress (OS). Enhancing the ability of endogenous antioxidants may be a more effective way to treat OS, and exosomes may play a role as targeted carriers. Exosomes are nanosized vesicles wrapped in biofilms which contain various complex RNAs and proteins. They are important intermediate carriers of intercellular communication and material exchange. In recent years, diagnosis and treatment with exosomes in cardiovascular diseases have gained considerable attention. Herein, we review the new findings of exosomes in the regulation of OS in coronary heart disease, discuss the possibility of exosomes as carriers for the targeted regulation of endogenous ROS generation, and compare the advantages of exosome therapy with those of stem-cell therapy. Finally, we explore several miRNAs found in exosomes against OS.

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Different effects of global osteopontin and macrophage osteopontin in glomerular injury

AJP Renal Physiology ◽

10.1152/ajprenal.00458.2017 ◽

2018 ◽

Vol 315 (4) ◽

pp. F759-F768 ◽

Cited By ~ 5

Author(s):

Jessica Trostel ◽

Luan D. Truong ◽

Carlos Roncal-Jimenez ◽

Makoto Miyazaki ◽

Shinobu Miyazaki-Anzai ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Kidney Injury ◽

Oxygen Species ◽

Glomerular Injury ◽

Tubulointerstitial Injury ◽

Crescent Formation ◽

Elevated Expression ◽

Toxin Receptor

Osteopontin (OPN) is a pro-and anti-inflammatory molecule that simultaneously attenuates oxidative stress. Both inflammation and oxidative stress play a role in the pathogenesis of glomerulonephritis and in the progression of kidney injury. Importantly, OPN is highly induced in nephritic kidneys. To characterize further the role of OPN in kidney injury we used OPN−/− mice in antiglomerular basement membrane reactive serum-induced immune (NTS) nephritis, an inflammatory and progressive model of kidney disease. Normal wild-type (WT) and OPN−/− mice did not show histological differences. However, nephritic kidneys from OPN−/− mice showed severe damage compared with WT mice. Glomerular proliferation, necrotizing lesions, crescent formation, and tubulointerstitial injury were significantly higher in OPN−/− mice. Macrophage infiltration was increased in the glomeruli and interstitium in OPN−/− mice, with higher expression of IL-6, CCL2, and chemokine CXCL1. In addition, collagen (Col) I, Col III, and Col IV deposition were increased in kidneys from OPN−/− mice. Elevated expression of the reactive oxygen species-generating enzyme Nox4 and blunted expression of Nrf2, a molecule that inhibits reactive oxygen species and inflammatory pathways, was observed in nephritic kidneys from OPN−/− mice. Notably, CD11b diphteria toxin receptor mice with NTS nephritis selectively depleted of macrophages and reconstituted with OPN−/− macrophages showed less kidney injury compared with mice receiving WT macrophages. These findings suggest that in global OPN−/− mice there is increased inflammation and redox imbalance that mediate kidney damage. However, absence of macrophage OPN is protective, indicating that macrophage OPN plays a role in the induction and progression of kidney injury in NTS nephritis.

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TRPC1 Deficiency Exacerbates Cerebral Ischemia/Reperfusion-Induced Neurological Injury by Potentiating Nox4-Derived Reactive Oxygen Species Generation

Cellular Physiology and Biochemistry ◽

10.1159/000495676 ◽

2018 ◽

Vol 51 (4) ◽

pp. 1723-1738 ◽

Cited By ~ 6

Author(s):

Ning Xu ◽

Hao Meng ◽

Tianyi Liu ◽

Yingli Feng ◽

Yuan Qi ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Severity Score ◽

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Neurological Injury ◽

Ros Generation ◽

Oxygen Species ◽

Neurological Severity Score

Background/Aims: Transient receptor potential cation channel 1 (TRPC1)-mediated the calcium (Ca2+) influx plays an important role in several brain disorders. However, the function of TRPC1 in ischemia/reperfusion (I/R)-induced neurological injury is unclear. Methods: Wild-type or TRPC1 knockout mice underwent middle cerebral artery occlusion for 90 min followed by 24 h of reperfusion. In an in vitro study, neuronal cells were treated with oxygen–glucose deprivation and reoxygenation (OGD/R) to mimic I/R. The intracellular Ca2+ concentration [Ca2+]i was measured by Fura 2-AM under a microscope. Cerebral infarct volume was measured by triphenyltetrazolium chloride staining. Neurological function was examined by neurological severity score, Morris water maze test, rotarod test and string test. Oxidative parameters were detected by malondialdehyde, glutathione peroxidase, and superoxide dismutase commercially available kits. The protein expression levels of TRPC1, Nox4, p22phox, p47phox, and p67phox were analyzed by western blotting. Results: Brain tissues from cerebral I/R mice showed decreased TRPC1 expression. Similarly, TRPC1 expression was reduced in HT22 cells upon exposure to OGD/R treatment, followed by decreased Ca2+ influx. However, TRPC1 overexpression reversed the OGD/R-induced decrease in [Ca2+]i. TRPC1 knockout significantly exacerbated I/R-induced brain infarction, edema, neurological severity score, memory impairment, neurological deficits, and oxidative stress. In contrast, TRPC1 upregulation inhibited the increase in reactive oxygen species (ROS) generation induced by OGD/R. Analysis of key subunits of the Nox family and mitochondrial ROS revealed that the effects of TRPC1 downregulation on oxidative stress were associated with activation of Nox4-containing NADPH oxidase. TRPC1 interacted with Nox4 and facilitated Nox4 protein degradation under OGD/R conditions. In addition, TRPC1 inhibition potentiated the OGD/R-induced translocation of p47phox and p67phox as well as the interaction between Nox4 and p47phox or p67phox, whereas TRPC1 overexpression had the opposite effects. Conclusion: TRPC1 deficiency potentiates ROS generation via Nox4-containing NADPH oxidase, which exacerbates cerebral I/R injury. TRPC1 may be a promising molecular target for the treatment of stroke.

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Targeting mitochondrial reactive oxygen species-mediated oxidative stress attenuates nicotine-induced cardiac remodeling and dysfunction

Scientific Reports ◽

10.1038/s41598-021-93234-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anand Ramalingam ◽

Siti Balkis Budin ◽

Norsyahida Mohd Fauzi ◽

Rebecca H. Ritchie ◽

Satirah Zainalabidin

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Cardiac Remodeling ◽

Ventricular Dysfunction ◽

Ischemia Reperfusion ◽

Oxygen Species ◽

Mitochondrial Reactive Oxygen Species ◽

Nicotine Administration ◽

Mitochondrial Ros ◽

Rat Hearts

AbstractLong-term nicotine intake is associated with an increased risk of myocardial damage and dysfunction. However, it remains unclear whether targeting mitochondrial reactive oxygen species (ROS) prevents nicotine-induced cardiac remodeling and dysfunction. This study investigated the effects of mitoTEMPO (a mitochondria-targeted antioxidant), and resveratrol (a sirtuin activator) , on nicotine-induced cardiac remodeling and dysfunction. Sprague–Dawley rats were administered 0.6 mg/kg nicotine daily with 0.7 mg/kg mitoTEMPO, 8 mg/kg resveratrol, or vehicle alone for 28 days. At the end of the study, rat hearts were collected to analyze the cardiac structure, mitochondrial ROS level, oxidative stress, and inflammation markers. A subset of rat hearts was perfused ex vivo to determine the cardiac function and myocardial susceptibility to ischemia–reperfusion injury. Nicotine administration significantly augmented mitochondrial ROS level, cardiomyocyte hypertrophy, fibrosis, and inflammation in rat hearts. Nicotine administration also induced left ventricular dysfunction, which was worsened by ischemia–reperfusion in isolated rat hearts. MitoTEMPO and resveratrol both significantly attenuated the adverse cardiac remodeling induced by nicotine, as well as the aggravation of postischemic ventricular dysfunction. Findings from this study show that targeting mitochondrial ROS with mitoTEMPO or resveratrol partially attenuates nicotine-induced cardiac remodeling and dysfunction.

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