A Glutathione Precursor Reduces Oxidative Injury to Cultured Embryonic Cardiomyocytes. (September 2020)

• Record Type: Journal Article
• Authors: Peterson, Darryl R.; Huang, Huiya; Peresada, Dmitriy; Sukowski, Ernest J.; White, Carl; Stefanov, Gospodin; Schweig, Lorene; Vazzalwar, Ramesh
• Is Part Of: American journal of therapeutics. Volume 27:Number 5(2020)
• Publication Date: 2020-09
• Subjects: glutathione -- gamma-glutamylcysteine -- ischemia–reperfusion injury; Chemotherapy -- Periodicals; Pharmacology -- Periodicals; 615.58
• DOI: 10.1097/MJT.0000000000000854
• Languages: English
• ISSNs: 1075-2765

Abstract

Abstract : 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 μm 2 ; 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.