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A Glutathione Precursor Reduces Oxidative Injury to Cultured Embryonic Cardiomyocytes

Darryl R Peterson1,2, Huiya Huang1, Dmitriy Peresada1

  • 1Disciplines of Physiology and Biophysics and.

American Journal of Therapeutics
|October 3, 2018
PubMed

Insights

The antioxidant gamma-L-glutamyl-L-cysteine (γGlu-Cys) effectively protects heart cells from oxidative damage during simulated ischemia-reperfusion. This glutathione precursor reduces apoptosis, offering a potential therapeutic strategy for conditions like birth asphyxia.

Area of Science:

  • Cardiovascular Research
  • Oxidative Stress Biology
  • Neonatal Medicine

Background:

  • Newborn infants face significant risks from oxidative stress, particularly after birth asphyxia.
  • Ischemia-reperfusion injury following asphyxia can cause severe brain and heart damage, leading to mortality or long-term disability.

Purpose of the Study:

  • To assess the protective effects of gamma-L-glutamyl-L-cysteine (γGlu-Cys), a glutathione precursor, against oxidative injury in cultured embryonic cardiomyocytes (H9c2 cells).

Main Methods:

  • H9c2 cells were subjected to 6-hour ischemia followed by 2-hour reperfusion, with or without 0.5 mM γGlu-Cys treatment.
  • Oxidative stress and apoptosis were quantified by measuring lactate dehydrogenase (LDH) release, cytosolic cytochrome c levels, and secondary lysosome formation via electron microscopy.

Main Results:

  • γGlu-Cys treatment significantly reduced LDH release (P=0.02) and secondary lysosome formation (P=0.01) compared to untreated controls.
  • The protective effect of γGlu-Cys on LDH release was comparable to that of a caspase inhibitor (P=0.67).
  • A significant increase in cytosolic cytochrome c post-reperfusion (P=0.01) was observed, further supporting γGlu-Cys's anti-apoptotic action.

Conclusions:

  • Gamma-L-glutamyl-L-cysteine (γGlu-Cys) demonstrates significant protective capabilities for cultured embryonic cardiomyocytes against apoptosis induced by oxidative injury.
  • γGlu-Cys acts as an effective antioxidant, mitigating damage associated with ischemia-reperfusion events in cardiac cells.
Abstract

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