title: Zinc pyrithione salvages reperfusion injury by inhibiting NADPH oxidase activation in cardiomyocytes.
abstract: 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 30 min or 16 h 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 p47(phox) phosphorylation indicating that ZPT directly protects cardiomyocytes from reperfusion injury by a mechanism that attenuates NADPH oxidase mediated intracellular oxidative stress.
authors.affiliation: Department of Pharmacology, Andhra University, Visakhapatnam, Andhra Pradesh, India.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Kasi
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Bodiga
authors.forename: Upendra Nadh
authors.initials: UN
authors.lastname: Kommuguri
authors.forename: Suneetha
authors.initials: S
authors.lastname: Sankuru
authors.forename: Vijaya Lakshmi
authors.initials: VL
authors.lastname: Bodiga
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019610:Cytoprotection; D008562:Membrane Glycoproteins / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008562:Membrane Glycoproteins; D009942:Organometallic Compounds; D011725:Pyridines; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C010423:pyrithione zinc