scholarly journals Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model

2018 ◽  
Vol 16 ◽  
pp. 205873921881266
Author(s):  
Walter A Trujillo-Rangel ◽  
Araceli Castillo-Romero ◽  
Sylvia E Totsuka-Sutto ◽  
Simón Q Rodríguez-Lara ◽  
Teresa A García-Cobián ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cellular Damage ◽  
Healthy Controls ◽  
Transcript Levels ◽  
Loss And Damage ◽  
Ischemic Tissue ◽  
Tnf Α ◽  
Hematoxylin And Eosin Stain

Ischemia–reperfusion is defined as cellular damage after the reperfusion of ischemic tissue, and it is likely to occur in relation to various diseases and surgical procedures. The purpose of this study was to evaluate the capability of atorvastatin to prevent oxidative damage and modulate the release of proinflammatory cytokines in rat hindlimb during ischemia–reperfusion injury. The animals were divided into 4 groups (ischemia–reperfusion + vehicle, ischemia–reperfusion + atorvastatin, sham, and healthy controls) with 15 rats per group. The animals were exposed to ischemia for 6 h, followed by 24 h, 7 days, and 14 days of reperfusion. Atorvastatin was administered by gavage 14 days before ischemia–reperfusion induction. We then measured the serum concentrations and mRNA transcript levels of TNF-α, IL-1β, IL-6, IL-10, SOD2, and CAT. Hematoxylin and eosin stain were performed for histological analyses. Animals subjected to ischemia–reperfusion showed increased serum and transcript levels of TNF-α, IL-1β, IL-6, and IL-10 expressions with a concurrent increase in mRNA transcripts levels compared with sham and healthy controls. Groups treated with atorvastatin showed a significant CAT increase in the first 24 h, but CAT levels decreased at 7 and 14 days. SOD2 enzyme increased in serum without significant changes in mRNA expression. Histological analysis showed inflammatory infiltrate, microhemorrhages, and distortion of the tissue architecture in the first 7 days. At 14 days, the tissue showed loss and damage to myocytes. However, animals treated with atorvastatin showed few histological changes and a decrease in inflammatory cytokines. No significant changes in NO2, NO3, or 8-OHdG were observed. Atorvastatin showed a protective effect on the inflammation and tissue damage induced by ischemia–reperfusion in the hindlimb. The antioxidant effect of atorvastatin in the hindlimb is already unclear, and further research is needed to elucidate the molecular mechanism of this drug in the extremities.

Neuroprotective effect of hydroxy safflor yellow A against cerebral ischemia-reperfusion injury in rats: putative role of mPTP

2016 ◽  
Vol 27 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Sruthi Ramagiri ◽  
Rajeev Taliyan
Keyword(s):  
Oxidative Damage ◽  
Protective Effect ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Radical Scavenger ◽  
Neuroprotective Effects ◽  
Y Maze ◽  
Tnf Α

AbstractHydroxy safflor yellow A (HSYA) has been translated clinically for cardiovascular diseases. HSYA is also greatly acknowledged for its protective effects against cerebral ischemic-reperfusion (I/R) injury. Although the precise mechanism of cerebral I/R injury is not fully understood, oxygen-derived free radicals and mitochondrial permeability transition pore (mPTP) opening during I/R injury are widely recognized as an important contributor to neuronal injury. Thus, we speculated that the neuroprotective effects of HSYA against cerebral I/R injury may be associated with mPTP modulation.Induction of I/R injury was achieved by 60 min of middle cerebral artery occlusion, followed by reperfusion for 24 h. For behavior and cognitive assessment, neurological scoring (NSS), rotarod, and Y-maze task were performed. Oxidative damage was measured in terms of markers such as malondialdehyde, reduced glutathione, and catalase levels and cerebral infarct volumes were quantified using 2,3,5-triphenyl tetrazolinium chloride staining. I/R injury-induced inflammation was determined using tumor necrosis factor-α (TNF-α) levels.Animals exposed to I/R injury showed neurological severity, functional and cognitive disability, elevated oxidative markers, and TNF-α levels along with large infarct volumes. HSYA treatment during onset of reperfusion ameliorated performance in NSS, rotarod and Y-maze attenuated oxidative damage, TNF-α levels, and infarction rate. However, treatment with carboxyatractyloside, an mPTP opener, 20 min before HSYA, attenuated the protective effect of HSYA.Our study confirmed that protective effect of HSYA may be conferred through its free radical scavenger action followed by inhibiting the opening of mPTP during reperfusion and HSYA might act as a promising therapeutic agent against cerebral I/R injury.

scholarly journals Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by the action on the Nrf2/HO-1 pathway

2021 ◽  
Vol 12 (1) ◽  
pp. 020-031
Author(s):  
Kong Fu ◽  
Miancong Chen ◽  
Hua Zheng ◽  
Chuanzi Li ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Learning Ability ◽  
Morris Water Maze Test ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background Morbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia. Methods The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays. Results The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues. Conclusions Our data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.

scholarly journals Remote ischemic per-conditioning protects against renal ischemia–reperfusion injury via suppressing gene expression of TLR4 and TNF-α in rat model

2019 ◽  
Vol 97 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Firouzeh Gholampour ◽  
Jamshid Roozbeh ◽  
Sahar Janfeshan ◽  
Zeinab Karimi
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Antioxidant Systems ◽  
Tlr4 Signaling ◽  
Tnf Α ◽  
Renal Ischemia Reperfusion Injury ◽  
Tlr4 Signaling Pathway

The pathogenesis of renal ischemia–reperfusion injury (IRI) involves both inflammatory processes and oxidative stress in the kidney. This study determined whether remote ischemic per-conditioning (RIPerC) is mediated by toll-like receptor 4 (TLR4) signaling pathway in rats. Renal IR injury was induced by occluding renal arteries for 45 min followed by 24 h of reperfusion. RIPerC included 4 cycles of 2 min of ischemia of the left femoral artery followed by 3 min of reperfusion performed at the start of renal ischemia. Rats were divided into sham, IR, and RIPerC groups. At the end of the reperfusion period, urine, blood and tissue samples were gathered. IR created kidney dysfunction, as ascertained by a significant decrease in creatinine clearance and a significant increase in sodium fractional excretion. These changes occurred in concert with a decrease in the activities of glutathione peroxidase, catalase, and superoxide dismutase with an increment in malondialdehyde levels, mRNA expression levels of TLR4 and tumor necrosis factor α (TNF-α), and histological damage in renal tissues. RIPerC treatment diminished all these changes. This study demonstrates that RIPerC has protective effects on the kidney after renal IR, which might be related to the inhibition of the TLR4 signaling pathway and augmentation of antioxidant systems.

scholarly journals Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2884 ◽  
Author(s):  
Eun-Jung In ◽  
Yuno Lee ◽  
Sushruta Koppula ◽  
Tae-Yeon Kim ◽  
Jun-Hyuk Han ◽  
...  
Keyword(s):  
Cell Death ◽  
Md Simulation ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Therapeutic Implications ◽  
Pathological Conditions ◽  
Tnf Α

Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none of them are currently in clinical use. In the present study, we identified a new compound, 4-({[5-(4-aminophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-N-(1,3-thiazol-2-yl) benzamide (NTB451), with significant inhibitory activity on the necroptosis induced by various triggers, such as tumor necrosis factor-α (TNF-α) and toll-like receptor (TLR) agonists. Mechanistic studies revealed that NTB451 inhibited phosphorylation and oligomerization of mixed lineage kinase domain like (MLKL), and this activity was linked to its inhibitory effect on the formation of the receptor interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3 complex. Small interfering RNA (siRNA)-mediated RIPK1 knockdown, drug affinity responsive target stability assay, and molecular dynamics (MD) simulation study illustrated that RIPK1 is a specific target of NTB451. Moreover, MD simulation showed a direct interaction of NTB451 and RIPK1. Further experiments to ensure that the inhibitory effect of NTB451 was restricted to necroptosis and NTB451 had no effect on nuclear factor-κB (NF-κB) activation or apoptotic cell death upon triggering with TNF-α were also performed. Considering the data obtained, our study confirmed the potential of NTB451 as a new necroptosis inhibitor, suggesting its therapeutic implications for pathological conditions induced by necroptotic cell death.

scholarly journals Assessing the Efficacy of Dietary Selenomethionine Supplementation in the Setting of Cardiac Ischemia/Reperfusion Injury

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 546 ◽  
Author(s):  
Leila Reyes ◽  
David P. Bishop ◽  
Clare L. Hawkins ◽  
Benjamin S. Rayner
Keyword(s):  
Cardiac Myocyte ◽  
Hypochlorous Acid ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Cytosolic Calcium ◽  
Cardiac Ischemia ◽  
Cellular Damage

Oxidative stress is a major hallmark of cardiac ischemia/reperfusion (I/R) injury. This partly arises from the presence of activated phagocytes releasing myeloperoxidase (MPO) and its production of hypochlorous acid (HOCl). The dietary supplement selenomethionine (SeMet) has been shown to bolster endogenous antioxidant processes as well as readily react with MPO-derived oxidants. The aim of this study was to assess whether supplementation with SeMet could modulate the extent of cellular damage observed in an in vitro cardiac myocyte model exposed to (patho)-physiological levels of HOCl and an in vivo rat model of cardiac I/R injury. Exposure of the H9c2 cardiac myoblast cell line to HOCl resulted in a dose-dependent increase in necrotic cell death, which could be prevented by SeMet supplementation and was attributed to SeMet preventing the HOCl-induced loss of mitochondrial inner trans-membrane potential, and the associated cytosolic calcium accumulation. This protection was credited primarily to the direct oxidant scavenging ability of SeMet, with a minor contribution arising from the ability of SeMet to bolster cardiac myoblast glutathione peroxidase (GPx) activity. In vivo, a significant increase in selenium levels in the plasma and heart tissue were seen in male Wistar rats fed a diet supplemented with 2 mg kg−1 SeMet compared to controls. However, SeMet-supplementation demonstrated only limited improvement in heart function and did not result in better heart remodelling following I/R injury. These data indicate that SeMet supplementation is of potential benefit within pathological settings where excessive HOCl is known to be generated but has limited efficacy as a therapeutic agent for the treatment of heart attack.

scholarly journals Role of cytokines in myocardial ischemia and reperfusion

1997 ◽  
Vol 6 (3) ◽  
pp. 175-183 ◽  
Author(s):  
H. S. Sharma ◽  
D. K. Das
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Membrane Damage ◽  
Inflammatory Cells ◽  
Myocardial Ischemia And Reperfusion ◽  
Tnf Α

Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia–reperfusion injury. Furthermore, ischemia–reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-α) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.

Vinpocetine protects liver against ischemia–reperfusion injury

2013 ◽  
Vol 91 (12) ◽  
pp. 1064-1070 ◽  
Author(s):  
Hala Fahmy Zaki ◽  
Rania Mohsen Abdelsalam
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Lipid ◽  
Cerebrovascular Disorders ◽  
Cellular Damage ◽  
Dependent Manner ◽  
Oxidative Stress Biomarkers ◽  
Serum Transaminases

Hepatic ischemia–reperfusion (IR) injury is a clinical problem that leads to cellular damage and organ dysfunction mediated mainly via production of reactive oxygen species and inflammatory cytokines. Vinpocetine has long been used in cerebrovascular disorders. This study aimed to explore the protective effect of vinpocetine in IR injury to the liver. Ischemia was induced in rats by clamping the common hepatic artery and portal vein for 30 min followed by 30 min of reperfusion. Serum transaminases and liver lactate dehydrogenase (LDH) activities, liver inflammatory cytokines, oxidative stress biomarkers, and liver histopathology were assessed. IR resulted in marked histopathology changes in liver tissues coupled with elevations in serum transaminases and liver LDH activities. IR also increased the production of liver lipid peroxides, nitric oxide, and inflammatory cytokines interleukin-1β and interleukin-6, in parallel with a reduction in reduced glutathione and interleukin-10 in the liver. Pretreatment with vinpocetine protected against liver IR-induced injury, in a dose-dependent manner, as evidenced by the attenuation of oxidative stress as well as inflammatory and liver injury biomarkers. The effects of vinpocetine were comparable with that of curcumin, a natural antioxidant, and could be attributed to its antioxidant and anti-inflammatory properties.

scholarly journals Oxidative Damage in Clinical Ischemia/Reperfusion Injury: A Reappraisal

2013 ◽  
Vol 19 (6) ◽  
pp. 535-545 ◽  
Author(s):  
Dorottya K. de Vries ◽  
Kirsten A. Kortekaas ◽  
Dimitrios Tsikas ◽  
Leonie G.M. Wijermars ◽  
Cornelis J.F. van Noorden ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion
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