Zinc pyrithione salvages reperfusion injury by inhibiting NADPH oxidase activation in cardiomyocytes

► Evidence for involvement of NADPH oxidase in hypoxia/reoxygenation injury in cardiomyocytes. ► Ability of zinc pyrithione administered just before reoxygenation to improve cell viability. ► Suppression of hypoxia/reoxygenation-induced NOX2 expression and p47phox phosphorylation by zinc pyrithione....

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2011-07, Vol.410 (2), p.270-275
Main Authors: Kasi, Viswanath, Bodiga, Sreedhar, Kommuguri, Upendra Nadh, Sankuru, Suneetha, Bodiga, Vijaya Lakshmi
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Cytoprotection
Membrane Glycoproteins - metabolism
Myocardial Reperfusion Injury - enzymology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - enzymology
NADPH oxidase
NADPH Oxidase 2
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - metabolism
Organometallic Compounds - pharmacology
Oxidative Stress - drug effects
p47phox
Phosphorylation - drug effects
Pyridines - pharmacology
Rats
Rats, Sprague-Dawley
Reperfusion injury
Zinc
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Summary:► Evidence for involvement of NADPH oxidase in hypoxia/reoxygenation injury in cardiomyocytes. ► Ability of zinc pyrithione administered just before reoxygenation to improve cell viability. ► Suppression of hypoxia/reoxygenation-induced NOX2 expression and p47phox phosphorylation by zinc pyrithione. Zinc pyrithione (ZPT), has a strong anti-apoptotic effect when administered just before reperfusion. Because oxidative stress has been proposed to contribute to myocardial reperfusion injury, we tested whether ZPT can reduce the production of reactive oxygen species during reoxygenation in cultured neonatal rat cardiac myocytes and evaluated the role of NADPH oxidase in hypoxia/reoxygenation (H/R) injury. The cells were subjected to 8h of simulated ischemia, followed by either 30min or 16h of reoxygenation. ZPT when started just before reoxygenation significantly reduced superoxide generation, LDH release and improved cell survival compared to H/R. Attenuation of the ROS production by ZPT paralleled its capacity to prevent pyknotic nuclei formation. In addition, ZPT reversed the H/R-induced expression of NOX2 and p47phox phosphorylation indicating that ZPT directly protects cardiomyocytes from reperfusion injury by a mechanism that attenuates NADPH oxidase mediated intracellular oxidative stress.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2011.05.130