Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia-reperfusion injury through depletion of glutathione.
Zn plays an important role in maintaining the anti-oxidant status within the heart and helps to counter the acute redox stress that occurs during myocardial ischaemia and reperfusion. Individuals with low Zn levels are at greater risk of developing an acute myocardial infarction; however, the impact of this on the extent of myocardial injury is unknown. The present study aimed to compare the effects of dietary Zn depletion with in vitro removal of Zn (N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)) on the outcome of acute myocardial infarction and vascular function. Male Sprague-Dawley rats were fed either a Zn-adequate (35 mg Zn/kg diet) or Zn-deficient (&lt;1 mg Zn/kg diet) diet for 2 weeks before heart isolation. Perfused hearts were subjected to a 30 min ischaemia/2 h reperfusion (I/R) protocol, during which time ventricular arrhythmias were recorded and after which infarct size was measured, along with markers of anti-oxidant status. In separate experiments, hearts were challenged with the Zn chelator TPEN (10 µm) before ischaemia onset. Both dietary and TPEN-induced Zn depletion significantly extended infarct size; dietary Zn depletion was associated with reduced total cardiac glutathione (GSH) levels, while TPEN decreased cardiac superoxide dismutase 1 levels. TPEN, but not dietary Zn depletion, also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide. These findings demonstrate that both modes of Zn depletion worsen the outcome from I/R but through different mechanisms. Dietary Zn deficiency, resulting in reduced cardiac GSH, is the most appropriate model for determining the role of endogenous Zn in I/R injury.
['Skene|Karen|K|', 'Walsh|Sarah K|SK|', 'Okafor|Oronne|O|', 'Godsman|Nadine|N|', 'Barrows|Charlotte|C|', 'Meier|Philip|P|', 'Gordon|Margaret J|MJ|', 'Beattie|John H|JH|', 'Wainwright|Cherry L|CL|0000-0003-1404-965X']
D000818:Animals D004032:Diet D005978:Glutathione D006321:Heart D008297:Male D017202:Myocardial Ischemia D015428:Myocardial Reperfusion Injury D051381:Rats D017207:Rats, Sprague-Dawley D015032:Zinc
Dietary zinc deficiency N N Vascular function 2-ethanediamine AAR area at risk BW body weight CAO coronary artery occlusion CPP coronary perfusion pressure Cu/Zn-SOD copper/zinc superoxide dismutase DTPA 2-[bis[2-[bis(carboxymethyl)amino]ethyl]amino]acetic acid HR heart rate I/R ischaemia–reperfusion KHB Kreb’s Henseleit buffer MCh methacholine N′ N′-tetrakis(2-pyridinylmethyl)-1 PF pair-fed SNP sodium nitroprusside SOD superoxide dismutase TPEN N VF ventricular fibrillation VPB ventricular premature beat VT ventricular tachycardia ZA zinc adequate ZD zinc deficient ZnT zinc transporter Glutathione: N Myocardial ischaemia–reperfusion injury N′-Tetrakis(2-pyridinylmethyl)-1