Myocardial adaptation to ischemia by oxidative stress induced by endotoxin

1995 ◽  
Vol 269 (4) ◽  
pp. C907-C916 ◽  
Author(s):  
N. Maulik ◽  
M. Watanabe ◽  
D. Engelman ◽  
R. M. Engelman ◽  
V. E. Kagan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Antioxidant Defense ◽  
Ischemia Reperfusion ◽  
Antioxidant Defense System ◽  
Left Ventricular ◽  
Antioxidant Enzyme Activities ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Antioxidant Reserve

In this study, we examined the effects of oxidative stress adaptation on myocardial ischemic reperfusion injury. Oxidative stress was induced by injecting endotoxin (0.5 mg/kg) into the rat. After 24 h, rats were killed, hearts were isolated, and the effects of ischemia-reperfusion were studied using an isolated working heart preparation. The development of oxidative stress was examined by assessing malonaldehyde production in the heart. The antioxidant defense system was studied by estimating antioxidant enzyme activities and ascorbate- as well as thiol-dependent antioxidant reserve. The results of our study indicated that endotoxin induced oxidative stress within 1 h of treatment; the stress was reduced progressively and steadily up to 24 h. The antioxidant enzymes superoxide dismutase, catalase, glutathione (GSH) peroxidase, and GSH reductase were lowered up to 2 h and then increased. Both thiol- and ascorbate-dependent antioxidant reserve were enhanced, but the enhancement of the former was only transitory. After 24 h, endotoxin provided adequate protection to the heart from the ischemic-reperfusion injury, as evidenced by improved left ventricular function and aortic flow. Our results suggest that the induction of oxidative stress by endotoxin-induced adaptive modification of the antioxidant defense in the heart, thereby reducing ischemic-reperfusion injury.

scholarly journals Oxidative Stress Underlies the Ischemia/Reperfusion-Induced Internalization and Degradation of AMPA Receptors

2021 ◽  
Vol 22 (2) ◽  
pp. 717
Author(s):  
Lindsay M. Achzet ◽  
Clara J. Davison ◽  
Moira Shea ◽  
Isabella Sturgeon ◽  
Darrell A. Jackson
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ampa Receptors ◽  
Neuronal Death ◽  
Ischemia Reperfusion ◽  
The United States ◽  
Delayed Neuronal Death ◽  
Rab Proteins ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion

Stroke is the fifth leading cause of death annually in the United States. Ischemic stroke occurs when a blood vessel supplying the brain is occluded. The hippocampus is particularly susceptible to AMPA receptor-mediated delayed neuronal death as a result of ischemic/reperfusion injury. AMPA receptors composed of a GluA2 subunit are impermeable to calcium due to a post-transcriptional modification in the channel pore of the GluA2 subunit. GluA2 undergoes internalization and is subsequently degraded following ischemia/reperfusion. The subsequent increase in the expression of GluA2-lacking, Ca2+-permeable AMPARs results in excitotoxicity and eventually delayed neuronal death. Following ischemia/reperfusion, there is increased production of superoxide radicals. This study describes how the internalization and degradation of GluA1 and GluA2 AMPAR subunits following ischemia/reperfusion is mediated through an oxidative stress signaling cascade. U251-MG cells were transiently transfected with fluorescently tagged GluA1 and GluA2, and different Rab proteins to observe AMPAR endocytic trafficking following oxygen glucose-deprivation/reperfusion (OGD/R), an in vitro model for ischemia/reperfusion. Pretreatment with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a superoxide dismutase mimetic, ameliorated the OGD/R-induced, but not agonist-induced, internalization and degradation of GluA1 and GluA2 AMPAR subunits. Specifically, MnTMPyP prevented the increased colocalization of GluA1 and GluA2 with Rab5, an early endosomal marker, and with Rab7, a late endosomal marker, but did not affect the colocalization of GluA1 with Rab11, a marker for recycling endosomes. These data indicate that oxidative stress may play a vital role in AMPAR-mediated cell death following ischemic/reperfusion injury.

Targeted disruption of peroxiredoxin 6 gene renders the heart vulnerable to ischemia-reperfusion injury

2006 ◽  
Vol 291 (6) ◽  
pp. H2636-H2640 ◽  
Author(s):  
Norbert Nagy ◽  
Gautam Malik ◽  
Aron B. Fisher ◽  
Dipak K. Das
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Wild Type ◽  
Ischemic Reperfusion Injury ◽  
Peroxiredoxin 6 ◽  
Ischemic Reperfusion

Peroxiredoxin 6 (Prdx6) is a novel peroxidase enzyme belonging to the Prdx family, which in mammals contains five more peroxiredoxins (Prdx1–Prdx5). Like glutathione peroxidase (GSHPx) and catalase, Prdx6 possesses H2O2-scavenging activities, and, like the former, it also removes hydroperoxides. Since significant amounts of catalase and GSHPx are present in the heart contributing toward the attenuation of H2O2 and hydroperoxides formed during ischemia-reperfusion injury and thereby providing cardioprotection, we asked whether Prdx6 also has any role in this process. In the present study we used Prdx6−/− mice to assess the role of Prdx6 in ischemic injury. Western blot analysis revealed the absence of any Prdx activity in the Prdx6−/− mouse heart, while the GSHPx-1 and catalase levels remained unchanged. Randomly selected hearts from Prdx6−/− mice and wild-type mice were subjected to 30 min of global ischemia followed by 120 min of reperfusion at normothermia. The hearts from the Prdx6−/− mice were more susceptible to ischemic reperfusion injury as evidenced by reduced recovery of left ventricular function, increased myocardial infarct size, and higher amount of apoptotic cardiomyocytes compared with wild-type mouse hearts. These Prdx6−/− hearts were also subjected to a higher amount of oxidative stress as evidenced by the presence of higher amount of malondialdehyde. The present study thus indicates a nonredundant role of Prdx6 in myocardial ischemic reperfusion injury as catalase, and GSHPx could not make up for the deficiency of Prdx6 activities.

scholarly journals Dose-dependent Effects of Perfluorocarbon Based Blood Substitute Perftoran on Cardyodinamics in Animal Model of Ischemia-reperfusion Injury

2021 ◽  
Author(s):  
Vladimir Jakovljevic ◽  
Sergey Vorobyev ◽  
Sergey Bolevich ◽  
Elena Morozova ◽  
Stefani Bolevich ◽  
...  
Keyword(s):  
Growth Rate ◽  
Reperfusion Injury ◽  
Rat Heart ◽  
Ex Vivo ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Isolated Rat

Abstract The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion in ex vivo-induced ischemic-reperfusion injury of an isolated rat heart. The first part of the study aims to determine the dose of 10% perfluoroemulsion (PFT) that will show the best cardioprotective effect in rats on ex vivo-induced ischemic / reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFT, the animals were divided into a control or experimental group, and depending on the application of a dose (8, 12, 16 ml / kg body weight) of saline or PFT. At a dose of 8 ml / kg, the results indicate statistically significantly lower values ​​of the maximum pressure growth rate in the group treated with 10% PFT compared to the control group treated with saline at R5 and R25 points. At a dose of 12 ml / kg, the maximum left ventricular pressure growth rate differed statistically significantly in the PFT group, ie there was an increase in this parameter at points R25 and R30, and the minimum left ventricular pressure growth rate in R15-R30 compared to saline-treated group. At a dose of 16 ml / kg, PFT also had a statistically significant effect on the change in cardiodynamic parameters in an isolated rat heart organ. Based on all the above, we can conclude that Peftoran administered immediately before ischemia (1 hour) has less positive effects on myocardial function in a model of an isolated rat heart compared to earlier administration (10 and 20 hours). Also, the effects of 10% peftoran solution are more pronounced if there is a longer period of time from application to ischemia, ie immediate application of peftoran before ischemia (1 hour) gave the weakest effects on the change of cardiodynamics of isolated rat heart.

scholarly journals Protective Effect of Pharmacological Preconditioning of Total Flavones of Abelmoschl Manihot on Cerebral Ischemic Reperfusion Injury in Rats

2007 ◽  
Vol 35 (04) ◽  
pp. 653-661 ◽  
Author(s):  
Ji-Yue Wen ◽  
Zhi-Wu Chen
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inos Mrna ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Infarction Volume ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
Pharmacological Preconditioning

The present study was to investigate the effect of pharmacological preconditioning of total flavones of Abelmoschl Manihot (TFA) on cerebral ischemic reperfusion injury in rats. Rat cerebral ischemia/reperfusion injury was induced by occluding the right middle cerebral artery (MCA). The infarct size was determined by staining with 2,3,5-triphenyl tetrazalium chloride (TTC). The serum malonaldehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) levels were measured by using spectrophotometry; Inducible NO synthase (iNOS) mRNA expression was detected by RT-PCR method. The percentage of cerebral infarction volume was 28.1 ± 0.8 in the model group, while TFA or nimodipine (Nim) pretreatment 36 hours prior to the ischemic insult significantly decreased the infarction volume. Increases of serum LDH activity and MDA level were observed after ischemia/reperfusion, but these changes were inhibited in rats pretreated with either TFA (20, 40, 80, 160 mg/kg) or Nim, indicating a delayed protective effect of TFA preconditioning on cerebral ischemic reperfusion injury. In addition, the serum NO level and the cerebral iNOS mRNA were up-regulated, suggesting a possible mechanism for the protective effect of TFA pretreatment on cerebral ischemic reperfusion injury.

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