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.

Abstract

Zinc (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 zinc (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 zinc depletion with in vitro removal of Zn (TPEN) on the outcome of acute myocardial infarction and vascular function. Male Sprague-Dawley rats were fed either a zinc adequate (ZA; 35mg Zn/kg diet) or zinc deficient (ZD; < 1mg Zn/kg diet) diet for two weeks prior to heart isolation. Perfused hearts were subjected to a thirty-minute ischaemia/two-hour 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 (10μM) prior to 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 SOD-1 levels. TPEN, but not dietary Zn depletion also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide (NO). These findings demonstrate that both modes of zinc 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.

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: https://doi.org/10.1017/S0007114519000230

• Journal Article Type: Article
• Acceptance Date: Jan 16, 2019
• Online Publication Date: Mar 21, 2019
• Publication Date: May 14, 2019
• Deposit Date: Feb 18, 2019
• Publicly Available Date: Feb 18, 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
• DOI: https://doi.org/10.1017/S0007114519000230
• Keywords: Dietary zinc deficiency; Myocardial ischaemia/reperfusion injury; Glutathione; 24 TPEN; Vascular function
• Public URL: http://hdl.handle.net/10059/3305
• Contract Date: Feb 18, 2019