Melatonin scavenges hydroxyl radical and protects isolated rat hearts from ischemic reperfusion injury

Kaneko, Shinji; Okumura, Kenji; Numaguchi, Yasushi; Matsui, Hideo; Murase, Kouhei; Mokuno, Shinji; Morishima, Itsuro; Hira, Kenji; Toki, Yukio; Itō, Takayuki; Hayakawa, Tetsuo

doi:10.1016/s0024-3205(00)00607-x

Cited by 86 publications

(72 citation statements)

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“…This protection is primarily due to the inhibition of apoptosis and necrosis, which was clearly revealed by our present finding that PC treatment decreased TUNEL-positive staining, Bax expression, caspase-3 activity, and infarct size. Several studies demonstrated that ROS produced in the reperfused myocardium cause oxidative stressmediated injury that is protected by antioxidants (10,11,15,16,35,38,44,48,50,61,63). Our present results showed that PC significantly suppressed ROS generation in hearts subjected to I/R.…”

Section: Discussionsupporting

confidence: 67%

C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

Khan¹,

Varadharaj²,

Ganesan³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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pusamy. C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling. Am J Physiol Heart Circ Physiol 290: H2136 -H2145, 2006. First published December 22, 2005 doi:10.1152/ajpheart.01072.2005.-We previously showed that C-phycocyanin (PC), an antioxidant biliprotein pigment of Spirulina platensis (a blue-green alga), effectively inhibited doxorubicininduced oxidative stress and apoptosis in cardiomyocytes. Here we investigated the cardioprotective effect of PC against ischemia-reperfusion (I/R)-induced myocardial injury in an isolated perfused Langendorff heart model. Rat hearts were subjected to 30 min of global ischemia at 37°C followed by 45 min of reperfusion. Hearts were perfused with PC (10 M) or Spirulina preparation (SP, 50 mg/l) for 15 min before the onset of ischemia and throughout reperfusion. After 45 min of reperfusion, untreated (control) hearts showed a significant decrease in recovery of coronary flow (44%), left ventricular developed pressure (21%), and rate-pressure product (24%), an increase in release of lactate dehydrogenase and creatine kinase in coronary effluent, significant myocardial infarction (44% of risk area), and TdT-mediated dUTP nick end labelpositive apoptotic cells compared with the preischemic state. PC or SP significantly enhanced recovery of heart function and decreased infarct size, attenuated lactate dehydrogenase and creatine kinase release, and suppressed I/R-induced free radical generation. PC reversed I/R-induced activation of p38 MAPK, Bax, and caspase-3, suppression of Bcl-2, and increase in TdT-mediated dUTP nick end label-positive apoptotic cells. However, I/R also induced activation of ERK1/2, which was enhanced by PC treatment. Overall, these results for the first time showed that PC attenuated I/R-induced cardiac dysfunction through its antioxidant and antiapoptotic actions and modulation of p38 MAPK and ERK1/2. oxidative stress; apoptosis; Spirulina; antioxidant; reactive oxygen species; free radicals THE HEART IS SUBJECTED to episodes of ischemia, followed by reperfusion, in a number of situations, including angina, myocardial infarction, and cardiac surgery. These stresses can result in cell injury and death. The pathogenesis of myocardial ischemia-reperfusion (I/R) injury involves the interplay of multiple mechanisms. Numerous studies have indicated the role of oxidative damage mediated by activation of xanthine oxidase and subsequent formation of reactive oxygen species (ROS), including O 2 Ϫ ⅐, H 2 O 2 , ⅐OH, and peroxynitrite, lipid peroxidation of myocardial membranes, action of iron, decrease in GSH, altered GSH-to-GSSG ratio, depletion of highenergy phosphates including ATP, depressed energy metabolism, and altered calcium homeostasis in the pathogenesis of

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Section: Discussionsupporting

confidence: 67%

C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

Khan¹,

Varadharaj²,

Ganesan³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…26,[30][31][32] In our experiments the protective effect of melatonin has also been demonstrated for cardiomyocytes treated by HOCl, irrespective of whether it was added before the oxidant treatment or after the oxidant removal. At the same time, some cardiomyocyte cytotoxicity of melatonin alone was observed (Figures 3, 4).…”

Section: Resultssupporting

confidence: 71%

2,3-Butanedione monoxime does not protect cardiomyocytes under oxidative stress

Przygodzki

Лапшина

Заводник

et al. 2006

Cell Biochem. Funct.

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Heart muscle ischemia-reperfusion provokes a pronounced cardiomyocyte oxidative stress. In the present study, we examined a possible protective effect of the cardioprotective drug, 2,3-butanedione monoxime (BDM), on the cultured neonatal cardiac myocytes exposed to oxidative stress induced by hypochlorous acid (HOCl), that may be formed by activated polymorphonuclear neutrophils in myocardium ischemic-reperfusion areas, and a useful model oxidant, tert-butyl hydroperoxide (tBHP). Using isolated rat cardiomyocytes substantial cytotoxicity of HOCl and tBHP was demonstrated: The concentrations of HOCl and tBHP causing a 50% decrease of cardiomyocyte cell viability were estimated to be 55 +/- 5 microM and 36 +/- 6 microM, respectively. The cell viability measured immediately after the tBHP oxidative treatment was significantly higher than that measured after 22 h of cell post-incubation in a fresh culture medium. This showed delayed cell death after removing tBHP. Hypochlorous acid treatment of cardiomyocytes did not change cellular viability during the cellular post-incubation in a fresh medium. Even a long-term (22 h) incubation of oxidatively damaged cardiomyocytes with BDM (5 mM) added after the HOCl removal did not recover the viability of the HOCl-exposed cells. In the presence of BDM, the cytotoxicity of HOCl significantly increased probably due to a direct reaction of both compounds and toxic chlorinated derivative formation. 2,3-Butanedione monoxime (5 mM) did not reduce cytotoxicity of tBHP, either. Such well-known antioxidative agents as melatonin or glutathione considerably prevented oxidant-induced cell death in a concentration-dependent manner.

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“…Since it has been shown that melatonin is capable of scavenging ROS in vitro [22] and in vivo [23], whereas interaction with H 2 O 2 is negligible [22], we used it to prove whether the effects of H 2 O 2 and Fe 3 + /NTA were indeed due to ROS generation (Fig. 2).…”

Section: Ros-mediated Injury: Influence On Cell Morphologymentioning

confidence: 99%

Na+–Ca2+ exchanger overexpression predisposes to reactive oxygen species-induced injury

Wagner

Seidler

Picht

et al. 2003

Cardiovascular Research

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Melatonin scavenges hydroxyl radical and protects isolated rat hearts from ischemic reperfusion injury

Cited by 86 publications

References 0 publications

C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

2,3-Butanedione monoxime does not protect cardiomyocytes under oxidative stress

Na+–Ca2+ exchanger overexpression predisposes to reactive oxygen species-induced injury

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