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A Glutathione Precursor Reduces Oxidative Injury to Cultured Embryonic Cardiomyocytes

Peterson, Darryl R. PhD*,1,2; Huang, Huiya MD, PhD1; Peresada, Dmitriy BS1; Sukowski, Ernest J. PhD1; White, Carl PhD1; Stefanov, Gospodin MD, PhD3; Schweig, Lorene MS, RN3; Vazzalwar, Ramesh MD3

doi: 10.1097/MJT.0000000000000854
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Background: Newborn infants are highly vulnerable to oxidative stress. Following birth asphyxia, oxidative injury due to ischemia–reperfusion can result in significant brain and heart damage, leading to death or long-term disability.

Study Question: The study objective was to evaluate the effectiveness of antioxidant gamma-L-glutamyl-L-cysteine (γGlu-Cys) in inhibiting oxidative injury to cultured embryonic cardiomyocytes (H9c2 cells).

Study Design: Control and γGlu-Cys–treated (0.5 mM) H9c2 cells were incubated under 6-hour ischemic conditions followed by 2-hour simulated reperfusion.

Measures and Outcomes: To quantify oxidative stress-induced apoptosis sustained by cardiomyocytes, lactate dehydrogenase (LDH) release and the presence of cytosolic cytochrome c were measured, as well as the number of secondary lysosomes visualized under electron microscopy.

Results: Compared to controls, H9c2 cells coincubated with γGlu-Cys during ischemia–reperfusion exhibited a significant reduction in both LDH release into the incubation medium [23.88 ± 4.08 (SE) vs. 9.95 ± 1.86% of total; P = 0.02] and the number of secondary lysosomes [0.070 ± 0.009 (SD) vs. 0.043 ± 0.004 per μm2; P = 0.01]. Inhibition of LDH release with γGlu-Cys was the same (P = 0.67) as that of a caspase inhibitor. The significant increase in cytosolic cytochrome c (P = 0.01) after ischemia–reperfusion simulation further supports γGlu-Cys's role in apoptosis prevention.

Conclusions: It is concluded that the glutathione precursor γGlu-Cys protects cultured embryonic cardiomyocytes from apoptosis-associated oxidative injury.

Departments of 1Physiology and Biophysics and

2Medicine, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL; and

3Department of Pediatrics, Division of Neonatology, Advocate Children's Hospital, Advocate Lutheran General Hospital, Park Ridge, IL.

Address for correspondence: Professor, Rosalind Franklin University, 3333 Green Bay Road, North Chicago, IL 60064. E-mail: Darryl.Peterson@rosalindfranklin.edu

Supported by the James R. and Helen D. Russell Institute for Research & Innovation Small Research Grants Program, Advocate Lutheran General Hospital, Park Ridge, IL.

D. R. Peterson (inventor and applicant) and Rosalind Franklin University of Medicine and Science (RFUMS) (applicant) have been awarded patents for the treatment of stroke. Although stroke differs from the pathological disorder investigated in the current study, one or more drugs used to treat stroke are also tested in the current study. Both D. R. Peterson and RFUMS may benefit financially on commercialization of the patents for treatment of stroke. D. R. Peterson is a faculty member at RFUMS and owns Harbor Biotechnology, LLC, a company that seeks to commercialize the patents referenced above for treatment of stroke. Further details may be obtained from D. R. Peterson on request. The remaining authors have no conflicts of interest to declare.

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