Detection of Oxidative DNA Damage to Ischemic Reperfused Rat Hearts by 8-Hydroxydeoxyguanosine Formation

Cordis, Gerald A.; Maulik, Gautam; Bagchi, Debasis; Riedel, Walter; Das, Dipak K.

doi:10.1006/jmcc.1998.0752

Cited by 59 publications

(32 citation statements)

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“…19 In our preliminary study, myocardial 8-OHdG content did not differ after 30 min or 2 h of reperfusion (data not shown). Accordingly, the myocardial 8-OHdG content was determined at 30 min of reperfusion in the present study.…”

Section: Assessment Of Myocardial Oxidative Damagementioning

confidence: 99%

“…18,23 Formation of 8-OHdG in the heart with IR progressively increases after reperfusion and is completely blocked by co-treatment with a free radical scavenger. 19 A large amount of oxygenderived free radicals are released from mitochondoria, the vessel walls, and leukocytes during reperfusion and therefore the antioxidant action of FV might be insufficient for cardioprotection from IR injury. Hayasaki et al reported that a reduction in myocardial oxidative stress was associated with attenuation of IR injury in mice deficient in the CC chemokine receptor 2.…”

Section: Antioxidant Property Of Fvmentioning

confidence: 99%

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Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Matsuki

Igawa

Nozawa

et al. 2006

Circ J

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arly reperfusion of an occluded coronary artery preserves myocardial viability and function by limiting the size of the myocardial infarct. 1,2 However, despite early reperfusion, myocardial ischemia-reperfusion (IR) injuries, including no reflow, stunning and reperfusion arrhythmias, sometimes occur, thereby attenuating the cardioprotective effect of reperfusion therapy. 3 Recent studies in experimental animals have demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) attenuate IR injury independently of their lipid-lowering action. [4][5][6][7][8] Statins have pleiotropic effects, including improvement of endothelial function by increased nitric oxide (NO) bioavailability, 9 and antioxidant 10 and antiinflammatory actions, 11 which may explain their attenuation of IR injury. The experimental result of cardioprotection by statins has therapeutic implication for patients with acute coronary syndrome who will be treated with reperfusion therapy; however, the time at which statin treatment was administered before IR varied from hours to days, and the Circulation Journal Vol.70, December 2006 results are conflicting. 5,12 It is not clear whether acute administration of statins at the onset of ischemia or reperfusion will prevent or attenuate the IR injury.Oxidative stress plays an important role in IR injury, and antioxidants such as superoxide dismutase and catalase could limit the infarct size in IR. 13 Statins are known to decrease free radical generation in the vascular wall 14,15 and myocardium, 16 which suggests that statins may protect the ischemic myocardium from IR injury via suppression of oxygen-derived free radicals produced upon reperfusion. Among the statins, fluvastatin (FV) has a potent free radical scavenging property derived from its chemical structure 17 and the purpose of the present study was to elucidate the effects of acute administration of FV and the role of its antioxidant property on IR injury in rats. MethodsThe experimental procedures followed the approved guidelines for animal experimentation at the University of Toyama. Myocardial IRMale Wistar rats weighing 270-380 g (n=103) were intubated under ether anesthesia and ventilated using a rodent respirator. The heart was exposed by left thoracotomy and the left coronary artery was ligated 2-3 mm from its origin Background Three-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are known to attenuate myocardial ischemia-reperfusion (IR) injury. Fluvastatin (FV) has a potent free radical scavenging action, but it is unclear whether the timing of FV administration could affect its cardioprotective effect or if the antioxidant property of FV might attenuate IR injury. Methods and Results IR was induced in rats by left coronary artery occlusion for 30 min followed by 24-h reperfusion. The rats were divided into 4 groups: oral FV group (10 mg/kg per day for 2 weeks before ischemia); iv, FV group (10 mg/kg) before ischemia; iv, FV group (10 mg/kg) before reperfusion; and control gr...

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Section: Assessment Of Myocardial Oxidative Damagementioning

confidence: 99%

Section: Antioxidant Property Of Fvmentioning

confidence: 99%

Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Matsuki

Igawa

Nozawa

et al. 2006

Circ J

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“…Collectively, these studies identify a central role for mitochondrial ROS generation during ischemia in the mitochondrial depolarization and subsequent cell death induced by ischemia and reperfusion in this model. reactive oxygen species; hypoxia; oxidants REACTIVE OXYGEN SPECIES (ROS) have been implicated as participants in the myocardial damage induced by ischemia-reperfusion (I/R) (1,4,9,17,21,25). Most studies have focused on the importance of oxidant stress generated during reperfusion, when a burst of ROS is generated after oxygen is reintroduced into the system after a prolonged period of ischemia (32,39).…”

mentioning

confidence: 99%

Cell death during ischemia: relationship to mitochondrial depolarization and ROS generation

Levraut

Iwase

Shao

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

194

139

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. Cell death during ischemia: relationship to mitochondrial depolarization and ROS generation. Am J Physiol Heart Circ Physiol 284: H549-H558, 2003. First published October 10, 2002 10.1152/ajpheart.00708.2002.-Ischemia-reperfusion injury induces cell death, but the responsible mechanisms are not understood. This study examined mitochondrial depolarization and cell death during ischemia and reperfusion. Contracting cardiomyocytes were subjected to 60-min ischemia followed by 3-h reperfusion. Mitochondrial membrane potential (⌬⌿m) was assessed with tetramethylrhodamine methyl ester. During ischemia, ⌬⌿m decreased to 24 Ϯ 5.5% of baseline, but no recovery was evident during reperfusion. Cell death assessed by Sytox Green was minimal during ischemia but averaged 66 Ϯ 7% after 3-h reperfusion. Cyclosporin A, an inhibitor of mitochondrial permeability transition, was not protective. However, pharmacological antioxidants attenuated the fall in ⌬⌿m during ischemia and cell death after reperfusion and decreased lipid peroxidation as assessed with C11-BODIPY. Cell death was also attenuated when residual O2 was scavenged from the perfusate, creating anoxic ischemia. These results suggested that reactive oxygen species (ROS) were important for the decrease in ⌬⌿m during ischemia. Finally, 143B-0 osteosarcoma cells lacking a mitochondrial electron transport chain failed to demonstrate a depletion of ⌬⌿m during ischemia and were significantly protected against cell death during reperfusion. Collectively, these studies identify a central role for mitochondrial ROS generation during ischemia in the mitochondrial depolarization and subsequent cell death induced by ischemia and reperfusion in this model. reactive oxygen species; hypoxia; oxidants REACTIVE OXYGEN SPECIES (ROS) have been implicated as participants in the myocardial damage induced by ischemia-reperfusion (I/R) (1,4,9,17,21,25). Most studies have focused on the importance of oxidant stress generated during reperfusion, when a burst of ROS is generated after oxygen is reintroduced into the system after a prolonged period of ischemia (32, 39). However, growing evidence suggests that oxidant stress begins during ischemia before reperfusion. For example, in cardiomyocytes subjected to simulated I/R, we observed (32, 33) an increase in ROS generation during ischemia followed by a large burst of oxidant production during the first few minutes after reoxygenation. In that model, antioxidants were more protective when given throughout the experiment than when given only at reperfusion, which supports the idea that oxidants generated during the ischemic phase contribute to cell injury and are important determinants of cell survival and recovery of function (2, 35).ROS generation cannot occur during ischemia unless some residual O 2 is still present. Previous studies using cardiomyocytes revealed that trace levels of O 2 are still detectable during simulated ischemia (PO 2 ϭ 5-7 mmHg). During ischemia, indexes of oxidant stress were attenuated by mitochondrial electron trans...

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“…25 8-OHdG is a sensitive and integral marker of oxidative damage to DNA. Cordis et al 26 reported that 8-OHdG is formed at the onset of reperfusion in the myocardium. Benidipine treatment reduces the level of hydroxyl radicals in reperfused myocardium in rabbit.…”

Section: Discussionmentioning

confidence: 99%

Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

et al. 2011

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Detection of Oxidative DNA Damage to Ischemic Reperfused Rat Hearts by 8-Hydroxydeoxyguanosine Formation

Cited by 59 publications

References 0 publications

Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Cell death during ischemia: relationship to mitochondrial depolarization and ROS generation

Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

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