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Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia-reperfusion injury through depletion of glutathione.

Skene, Karen; Walsh, Sarah K.; Okafor, Oronne; Godsman, Nadine; Barrows, Charlotte; Meier, Philip; Gordon, Margaret J.; Beattie, John H.; Wainwright, Cherry L.


Karen Skene

Sarah K. Walsh

Oronne Okafor

Nadine Godsman

Charlotte Barrows

Philip Meier

Margaret J. Gordon

John H. Beattie

Cherry L. Wainwright


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 (less than 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.

Journal Article Type Article
Publication Date May 14, 2019
Journal British journal of nutrition
Print ISSN 0007-1145
Electronic ISSN 1475-2662
Publisher Cambridge University Press (CUP)
Peer Reviewed Peer Reviewed
Volume 121
Issue 9
Pages 961-973
Institution Citation SKENE, K., WALSH, S.K., OKAFOR, O., GODSMAN, N., BARROWS, C., MEIER, P., GORDON, M.J., BEATTIE, J.H. and WAINWRIGHT, C.L. 2019. Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia-reperfusion injury through depletion of glutathione. British journal of nutrition [online], 121(9), pages 961-973. Available from:
Keywords Dietary zinc deficiency; Myocardial ischaemia/reperfusion injury; Glutathione; 24 TPEN; Vascular function


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