Protective effect of gamma-glutamylcysteinylethyl ester on dysfunction of the selenium-deficient rat heart.

We investigated the protective effect of intracellular GSH against cardiac dysfunction in selenium (Se)-deficient neonatal rats and cultured fetal rat myocytes. A Se-deficient diet with or without daily subcutaneous injections of gamma-glutamylcysteinylethyl ester (gammay-GCE) (a membrane-permeating GSH precursor) was given to rats from gestation day 4 via the dam to postnatal day 14. Se deficiency induced a 62% incidence of electrocardiographic abnormalities such as sinus arrhythmias or extrasystole, a 63% reduction in dP/dt in the left ventricle, and an increase in thiobarbituric acid reacting substances (TBARS), but no ultrastructural cardiac lesions were observed. Administration of gamma-GCE increased the intracellular GSH concentration ([GSH]i) of both neonatal rat hearts and cultured fetal rat cardiac myocytes. gamma-GCE-like sodium selenite prevented the cardiac dysfunction and the TBARS increment. gamma-GCE also prevented H2O2 toxicity in the cultured myocytes. The Vmax, but not the Km, for GSH of Se-dependent GSH peroxidase (Se-Gpx) activity in Se-deficient rat heart homogenates was one-third that of normal rat heart homogenates. Although gamma-GCE did not affect the Se-Gpx Vmax and Km for GSH, it did induce a substantial and significant increase in [GSH]i, which was postulated to increase the velocity of H2O2 decomposition by Se-Gpx activity 1.6-fold. These data suggest that the increase in [GSH]i may have played a role in preventing the TBARS increase and cardiac dysfunction in Se-deficient rats.