Selenium repletion and glutathione peroxidase— differential effects on plasma and red blood cell enzyme activity

Abstract

We studied three children with chronic gastrointestinal disease who had been on intravenous hyperalimentation for periods of time ranging from 4 to 23 months. Each child was found to have low plasma and red blood cell glutathione peroxidase activity. This was associated, in the two children tested, with a marked deficiency of serum selenium. Their plasma glutathione peroxidase levels ranged between 4 and 24% of normal and their red blood cell levels ranged between 4 and 14% of normal. The intravenous alimentation was then supplemented with sodium selenite (240 micrograms Se/d). Within 4-5 weeks, the plasma glutathione peroxidase activity returned to normal. Red cell glutathione peroxidase activity remained essentially unchanged for 4-6 weeks, after which it increased over the following 3-4 months. Red cells were separated by density on a continuous Percoll-diatrizoate gradient. In normal individuals, the specific activity of glutathione peroxidase did not differ across the gradient despite a 2.5-fold difference in the specific activity of pyruvate kinase. When studied initially, glutathione peroxidase activity from the deficient patients did not change across the gradient. As the red cell enzyme activity increased with selenium repletion, the highest specific activity was initially found at the top of the gradient (youngest cells). After 3-4 months of supplementation, the specific activity became equal across the gradient. Thus, with selenium repletion, there is a rapid increase in plasma glutathione peroxidase activity, a 4-6 week lag prior to an increase in red cell enzyme activity, and the increase in red cell activity is due to newly synthesized red cells made in the presence of selenium.

Selenium and Glutathione Peroxidase Levels in Premature Infants in a Low Selenium Community (Christchurch, New Zealand)

“…Thus, they respond slowly and give information on longer term selenium status. Plasma levels equilibrate within a few days, so they can respond quickly to any change in body stores (9,35,36 were not apparent for red cells, probably because few infants were over 3 mo old and effects of red cell turnover were not apparent. However, our study of term infants up to I y old showed that changes in red cells lag 2-3 mo behind changes in plasma (31).…”

Glutathione peroxidase protein. Absence in selenium deficiency states and correlation with enzymatic activity.

“…Samples oferythrocytes were obtained from a selenium-deficient individual during the course of selenium repletion as previously described (12). Selenium-deficient HL-60 were grown as previously described (16).…”

“…Supplementation of both animals and patients with selenium results in an increase in cellular levels of GSHPx activity (3-4, 8-1 1). We have recently shown that when patients deficient in selenium and GSHPx are supplemented with intravenous selenous acid, there is a time-dependent recovery in their erythrocyte GSHPx activity occurring over 3-4 mo and that this recovery occurs only in cells made in the presence of selenium (12). Since all of the above studies were performed using an enzymatic assay for GSHPx activity, it was not possible to determine whether the GSHPx protein was synthesized in the absence ofselenium.…”

Enhancement of Hydroxyl Radical Formation from Superoxide Anion Radical in the Presence of Organic Selenium Compounds.

“…GPX catalyzes the reduced reaction of hydrogen peroxide or organic hydroperoxides with GSH, and plays an important role in the protection of a cell from oxidative damage. Both experimental and clinical selenium deficiency cause a decrease of GPX activity 31,32) , resulting in enhancement of the toxicity induced by AOS.…”