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

Karen Skene, Sarah K Walsh, Oronne Okafor, Nadine Godsman, Charlotte Barrows, Philip Meier, Margaret J Gordon, John H Beattie, Cherry L Wainwright (Corresponding Author)

Research output: Contribution to journalArticle

Abstract

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 (<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.
Original languageEnglish
Pages (from-to)961-973
Number of pages13
JournalBritish Journal of Nutrition
Volume121
Issue number9
Early online date21 Mar 2019
DOIs
Publication statusPublished - 14 May 2019

Fingerprint

Myocardial Reperfusion Injury
Reperfusion Injury
Myocardial Ischemia
Glutathione
Zinc
Ischemia
ethylenediamine
Diet
Oxidants
Reperfusion
Blood Vessels
Cardiac Arrhythmias
Myocardial Infarction
Myocardial Reperfusion
Chelating Agents
Oxidation-Reduction
Nitric Oxide
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
Wounds and Injuries

Keywords

  • Dietary zinc deficiency
  • Glutathione: N,N,N′,N′-Tetrakis(2-pyridinylmethyl)-1,2-ethanediamine
  • Myocardial ischaemia-reperfusion injury
  • Vascular function

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Medicine (miscellaneous)

Cite this

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 (Corresponding Author).

In: British Journal of Nutrition, Vol. 121, No. 9, 14.05.2019, p. 961-973.

Research output: Contribution to journalArticle

Skene, Karen ; Walsh, Sarah K ; Okafor, Oronne ; Godsman, Nadine ; Barrows, Charlotte ; Meier, Philip ; Gordon, Margaret J ; Beattie, John H ; Wainwright, Cherry L. / Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia/reperfusion injury through depletion of glutathione. In: British Journal of Nutrition. 2019 ; Vol. 121, No. 9. pp. 961-973.
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N2 - 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 (<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.

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