scholarly journals Preconditioning and Acute Effects of Flavonoids in Protecting Cardiomyocytes from Oxidative Cell Death

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Masoumeh Akhlaghi ◽  
Brian Bandy
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Relative Effectiveness ◽  
Epigallocatechin Gallate ◽  
Short Term ◽  
Higher Doses

While flavonoids can reportedly protect against cardiac ischemia-reperfusion injury, the relative effectiveness of different flavonoids and the mechanisms involved are unclear. We compared protection by different flavonoids using rat embryonic ventricular H9c2 cells subjected to simulated ischemia-reperfusion (IR) and totert-butyl hydroperoxide (t-buOOH). Characterization of the IR model showed the relative contributions of glucose, serum, and oxygen deprivation to cell death. With long-term (2-3 day) pretreatment before IR the best protection was given by catechin, epigallocatechin gallate, proanthocyanidins, and ascorbate, which protected at all doses. Quercetin protected (34%) at 5 μM but was cytotoxic at higher doses. Cyanidin protected mildly (10–15%) at 5 and 20 μM, while delphinidin had no effect at 5 μM and was cytotoxic at higher doses. Comparing long-term and acute protection by catechin, a higher concentration was needed for benefit with acute (1 hr) pretreatment. With a pure oxidative stress (t-buOOH) only quercetin significantly protected with 3-day pretreatment, while with short-term (1 h) pretreatments protection was best with quercetin and epigallocatechin gallate. The results suggest catechins to be especially useful as IR preconditioning agents, while quercetin and epigallocatechin gallate may be the most protective acutely in situations of oxidative stress.

scholarly journals Oxidative Stress-Associated Impairment of Proteasome Activity during Ischemia–Reperfusion Injury

2000 ◽  
Vol 20 (10) ◽  
pp. 1467-1473 ◽  
Author(s):  
Jeffrey N. Keller ◽  
Feng F. Huang ◽  
Hong Zhu ◽  
Jin Yu ◽  
Ye-Shih Ho ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Proteasome Inhibition ◽  
Cerebral Ischemia Reperfusion ◽  
Proteasome Subunits ◽  
Cerebral Ischemia Reperfusion Injury

Numerous studies indicate a role for oxidative stress in the neuronal degeneration and cell death that occur during ischemia–reperfusion injury. Recent data suggest that inhibition of the proteasome may be a means by which oxidative stress mediates neuronal cell death. In the current study, the authors demonstrate that there is a time-dependent decrease in proteasome activity, which is not associated with decreased expression of proteasome subunits, after cerebral ischemia–reperfusion injury. To determine the role of oxidative stress in mediating proteasome inhibition, ischemia–reperfusion studies were conducted in mice that either overexpressed the antioxidant enzyme glutathione peroxidase [GPX 1(+)], or were devoid of glutathione peroxidase activity (GPX −/−). After ischemia–reperfusion, GPX 1(+) mice displayed decreased infarct size, attenuated neurologic impairment, and reduced levels of proteasome inhibition compared with either GPX −/− or wild type mice. In addition, GPX 1(+) mice displayed lower levels of 4-hydroxynonenal-modified proteasome subunits after ischemia–reperfusion injury. Together, these data indicate that proteasome inhibition occurs during cerebral ischemia–reperfusion injury and is mediated, at least in part, by oxidative stress.

scholarly journals The long-term protective effect of tadalafil on spermatogenesis following testicular ischemia-reperfusion injury in a rat model

2020 ◽  
Author(s):  
Bomi Kim ◽  
EunHye Lee ◽  
BoHyun Yoon ◽  
So Young Chun ◽  
Jae-Wook Chung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Rat Model ◽  
Testicular Torsion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Group A ◽  
Testicular Ischemia

Abstract Background Testicular torsion is a urological emergency in which misdiagnosis and inappropriate treatment can lead to testicular atrophy and male infertility owing to ischemia-reperfusion injury (IRI). Although experimental studies of testicular torsion have been preceded, promising therapeutic agents based on the long-term effect for spermatogenesis have not been identified in testicular ischemia reperfusion injury (IRI) animal model. Tadalafil, one of the phosphodiesterase-5 inhibitors commonly used in the treatment of erectile dysfunction, has recently reported a protective effect against IRI in several organs. In this study, we evaluated the long-term protective effect of tadalafil for spermatogenesis in a rat testicular IRI model. Methods Forty-eight adolescent Sprague–Dawley rats were divided into 6 groups (A-F). Sham operation was performed in group A. Group B received surgical 720-degree torsion of the left testis without any medication. Groups C, D, E, and F were operated surgical torsion with tadalafil at varying doses (0.3 mg/kg, 1.0 mg/kg) and durations (single or daily administration for 4 weeks). Detorsion was performed after 3 hour of torsion in all rats except the sham group. Four weeks after operation, both testes were evaluated of spermatogenesis using Johnsen scoring. To evaluate the protective effect of tadalafil against oxidative stress by IRI, malondialdehyde (MDA) and superoxide dismutase (SOD) level were analyzed via ELISA in both testes 4 hour after detorsion in the same experiments as in group A, B, and C. Results For the evaluation of spermatogenesis according to doses, the groups with high-dose tadalafil showed a higher Johnsen scores than low-dose counterparts. The groups with daily administration for 4weeks were observed a higher Johnsen scores than those given a single administration. Furthermore, molecular markers (MDA and SOD) related with oxidative stress and histopathologic findings showed remarkable improvement after tadalafil administration. Conclusion Tadalafil alleviated long-term deterioration of spermatogenesis and oxidative stress by restoring antioxidant status after testicular IRI rat model. Furthermore, it demonstrated a protective effect against testicular IRI in a time- and dose-dependent manner.

Distinct Roles for Sarcolemmal and Mitochondrial Adenosine Triphosphate-sensitive Potassium Channels in Isoflurane-induced Protection against Oxidative Stress

2006 ◽  
Vol 105 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Jasna Marinovic ◽  
Zeljko J. Bosnjak ◽  
Anna Stadnicka
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Adenosine Triphosphate ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Mechanism ◽  
Trypan Blue Exclusion ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Cardiac Preconditioning

Background Cardiac preconditioning, including that induced by halogenated anesthetics, is an innate protective mechanism against ischemia-reperfusion injury. The adenosine triphosphate-sensitive potassium (K(ATP)) channels are considered essential in preconditioning mechanism. However, it is unclear whether K(ATP) channels are triggers initiating the preconditioning signaling, and/or effectors responsible for the cardioprotective memory and activated during ischemia-reperfusion. Methods Adult rat cardiomyocytes were exposed to oxidative stress with 200 microM H(2)O(2) and 100 microM FeSO4. Myocyte survival was determined based on morphologic characteristics and trypan blue exclusion. To induce preconditioning, the myocytes were pretreated with isoflurane. The involvement of sarcolemmal and mitochondrial K(ATP) channels was investigated using specific inhibitors HMR-1098 and 5-hydroxydecanoic acid. Data are expressed as mean +/- SD. Results Oxidative stress induced cell death in 47 +/- 14% of myocytes. Pretreatment with isoflurane attenuated this effect to 26 +/- 8%. Blockade of the sarcolemmal K(ATP) channels abolished the protection by isoflurane pretreatment when HMR-1098 was applied throughout the experiment (50 +/- 21%) or only during oxidative stress (50 +/- 12%), but not when applied during isoflurane pretreatment (29 +/- 13%). Inhibition of the mitochondrial K(ATP) channels abolished cardioprotection irrespective of the timing of 5-hydroxydecanoic acid application. Cell death was 42 +/- 23, 45 +/- 23, and 46 +/- 22% when 5-hydroxydecanoic acid was applied throughout the experiment, only during isoflurane pretreatment, or only during oxidative stress, respectively. Conclusion The authors conclude that both sarcolemmal and mitochondrial K(ATP) channels play essential and distinct roles in protection afforded by isoflurane. Sarcolemmal K(ATP) channel seems to act as an effector of preconditioning, whereas mitochondrial K(ATP) channel plays a dual role as a trigger and an effector.

scholarly journals The Redox Modulating Sonlicromanol Active Metabolite KH176m and the Antioxidant MPG Protect Against Short-Duration Cardiac Ischemia-Reperfusion Injury

2021 ◽  
Author(s):  
Yang Xiao ◽  
Karen Yim ◽  
Hong Zhang ◽  
Diane Bakker ◽  
Rianne Nederlof ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Clinical Stage ◽  
Cardiac Ischemia ◽  
Oxidative Stress Marker ◽  
Thioredoxin System ◽  
Ldh Release

Abstract Purpose Sonlicromanol is a phase IIB clinical stage compound developed for treatment of mitochondrial diseases. Its active component, KH176m, functions as an antioxidant, directly scavenging reactive oxygen species (ROS), and redox activator, boosting the peroxiredoxin-thioredoxin system. Here, we examined KH176m’s potential to protect against acute cardiac ischemia-reperfusion injury (IRI), compare it with the classic antioxidant N-(2-mercaptopropionyl)-glycine (MPG), and determine whether protection depends on duration (severity) of ischemia. Methods Isolated C56Bl/6N mouse hearts were Langendorff-perfused and subjected to short (20 min) or long (30 min) ischemia, followed by reperfusion. During perfusion, hearts were treated with saline, 10 μM KH176m, or 1 mM MPG. Cardiac function, cell death (necrosis), and mitochondrial damage (cytochrome c (CytC) release) were evaluated. In additional series, the effect of KH176m treatment on the irreversible oxidative stress marker 4-hydroxy-2-nonenal (4-HNE), formed during ischemia only, was determined at 30-min reperfusion. Results During baseline conditions, both drugs reduced cardiac performance, with opposing effects on vascular resistance (increased with KH176m, decreased with MPG). For short ischemia, KH176m robustly reduced all cell death parameters: LDH release (0.2 ± 0.2 vs 0.8 ± 0.5 U/min/GWW), infarct size (15 ± 8 vs 31 ± 20%), and CytC release (168.0 ± 151.9 vs 790.8 ± 453.6 ng/min/GWW). Protection by KH176m was associated with decreased cardiac 4-HNE. MPG only reduced CytC release. Following long ischemia, IRI was doubled, and KH176m and MPG now only reduced LDH release. The reduced protection against long ischemia was associated with the inability to reduce cardiac 4-HNE. Conclusion Protection against cardiac IRI by the antioxidant KH176m is critically dependent on duration of ischemia. The data suggest that with longer ischemia, the capacity of KH176m to reduce cardiac oxidative stress is rate-limiting, irreversible ischemic oxidative damage maximally accumulates, and antioxidant protection is strongly diminished.

Adaptive Responses to the Stress Induced by Hyperthermia or Hydrogen Peroxide in Human Fibroblasts

2003 ◽  
Vol 228 (5) ◽  
pp. 491-498 ◽  
Author(s):  
S. Grasso ◽  
C. Scifo ◽  
V. Cardile ◽  
R. Gulino ◽  
M. Renis
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Human Fibroblasts ◽  
Membrane Integrity ◽  
Adaptive Responses ◽  
Mitochondrial Potential ◽  
Cell Membrane Integrity

Perturbation of oxidant/antioxidant cellular balance, induced by cellular metabolism and by exogenous sources, causes deleterious effects to proteins, lipids, and nucleic acids, leading to a condition named “oxidative stress” that is involved in several diseases, such as cancer, ischemia-reperfusion injury, and neurodegenerative disorders. Among the exogenous agents, both H2O2 and hyperthermia have been implicated in oxidative stress promotion linked with the activation of apoptotic or necrotic mechanisms of cell death. The goal of this work was to better understand the involvement of some stress-related proteins in adaptive responses mounted by human fibroblasts versus the oxidative stress differently induced by 42°C hyperthermia or H2O2. The research was developed, switching off inducible nitric oxide synthase (iNOS) expression through antisense oligonucleotide transfection by studying the possible coregulation in the expression of HSP32 (also named HO-1), HSP70, and iNOS and their involvement in the induction of DNA damage. Several biochemical parameters, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), reactive oxygen species formation, glutathione levels, immunocytochemistry analysis of iNOS, HSP70, and HO-1 levels, genomic DNA fragmentation (HALO/COMET assay), and transmembrane mitochondrial potential (ΔΨ) were examined. Cells were collected immediately at the end of the stress-inducing treatment. The results, confirming the pleiotropic function of i-NOS, indicate that: (i) HO-1/HSP32, HSP70, and iNOS are finely tuned in their expression to contribute all together, in human fibroblasts, in ameliorating the resistance to oxidative stress damage; (ii) ROS exposure, at least in hyperthermia, in human fibroblasts contributes to growth arrest more than to apoptosis activation; and (iii) mitochondrial dysfunction, in presence of iNOS inhibition seems to be clearly involved in apoptotic cell death of human fibroblasts after H2O2 treatment, but not after hyperthermia.

scholarly journals New Insights in Mechanisms and Therapeutics for Short- and Long-Term Impacts of Hepatic Ischemia Reperfusion Injury Post Liver Transplantation

2021 ◽  
Vol 22 (15) ◽  
pp. 8210
Author(s):  
Hui Liu ◽  
Kwan Man
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Cancer Recurrence ◽  
Short Term ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Liver transplantation has been identified as the most effective treatment for patients with end-stage liver diseases. However, hepatic ischemia reperfusion injury (IRI) is associated with poor graft function and poses a risk of adverse clinical outcomes post transplantation. Cell death, including apoptosis, necrosis, ferroptosis and pyroptosis, is induced during the acute phase of liver IRI. The release of danger-associated molecular patterns (DAPMs) and mitochondrial dysfunction resulting from the disturbance of metabolic homeostasis initiates graft inflammation. The inflammation in the short term exacerbates hepatic damage, leading to graft dysfunction and a higher incidence of acute rejection. The subsequent changes in the graft immune environment due to hepatic IRI may result in chronic rejection, cancer recurrence and fibrogenesis in the long term. In this review, we mainly focus on new mechanisms of inflammation initiated by immune activation related to metabolic alteration in the short term during liver IRI. The latest mechanisms of cancer recurrence and fibrogenesis due to the long-term impact of inflammation in hepatic IRI is also discussed. Furthermore, the development of therapeutic strategies, including ischemia preconditioning, pharmacological inhibitors and machine perfusion, for both attenuating acute inflammatory injury and preventing late-phase disease recurrence, will be summarized in the context of clinical, translational and basic research.

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