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; 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.
Subject(s)
Antioxidants/pharmacology , Asphyxia Neonatorum/drug therapy , Dipeptides/pharmacology , Myocardial Reperfusion Injury/prevention & control , Myocytes, Cardiac/drug effects , Animals , Antioxidants/therapeutic use , Apoptosis/drug effects , Asphyxia Neonatorum/complications , Cell Line , Dipeptides/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Embryo, Mammalian , Humans , Infant, Newborn , Myocardial Reperfusion Injury/etiology , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , RatsABSTRACT
OBJECTIVE: To compare the utility of procalcitonin (PCT) vs C-reactive protein (CRP) as indicators of late-onset neonatal sepsis in very low birth weight (VLBW) infants. METHODS: PCT and CRP levels were measured in VLBW infants with suspected sepsis and controls. Comparisons were made between infected vs noninfected infants. Using cutoff values of 0.5 and 1.0 ng/ml for PCT and 0.8 mg/dl for CRP, sensitivity, specificity, positive and negative predictive values were calculated to evaluate these assays as potential predictors of late-onset sepsis. RESULTS: A total of 67 infants were evaluated. Mean PCT levels were significantly higher in the infected group (5.41 ng/ml) compared to the noninfected group (0.43 ng/ml) (p < 0.001). At a cut off value of 0.5 ng/ml, the sensitivity of PCT was 97%, whereas that of CRP was 73% in predicting late-onset sepsis. At a PCT cutoff of 1.0 ng/ml, sensitivities of PCT and CRP were similar (72% each). CONCLUSION: PCT (0.5 ng/ml) is more sensitive than CRP in predicting late-onset sepsis in VLBW infants.
