Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase

When hemolyzates from erythrocytes of selenium-deficient rats were incubated in vitro in the presence of ascorbate or H(2)O(2), added glutathione failed to protect the hemoglobin from oxidative damage. This occurred because the erythrocytes were practically devoid of glutathione-peroxidase activity. Extensively purified preparations of glutathione peroxidase contained a large part of the (75)Se of erythrocytes labeled in vivo. Many of the nutritional effects of selenium can be explained by its role in glutathione peroxidase.

https://science.sciencemag.org/content/sci/179/4073/588.full.pdf

Selenium: Biochemical Role as a Component of Glutathione Peroxidase

Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues

During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.

https://www.pnas.org/content/pnas/78/11/6858.full.pdf

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

Experiments were conducted with male rats to quantitate the relation ship between dietary selenium (Se) intake and the amount of the enzyme glutathione peroxidase (GSH-Px) in erythrocytes and liver. Weanling male rats were fed torula yeast-based diets with 0, 0.05, 0.1, 0.5, 1.0, or 5.0 ppm Se supplemented as sodium selenite. Liver GSH-Px fell to undetectable levels (<1% of that found in the weanling rats) within 24 days in the O ppm Se group; feeding 0.1 ppm Se, or greater, caused liver GSH-Px to increase above that found in the weanling rats. The erythrocyte GSH-Px response to lack of dietary Se was somewhat smaller in magnitude and more gradual; however, only 21% of initial erythrocyte GSH-Px activity remained in the unsupplemented group after 66 days. Increased dietary Se resulted in corresponding increases of erythrocyte GSH-Px activity. Resupplementing with 0.1, 0.5, or 5.0 ppm Se elevated the depressed erythrocyte GSH-Px levels of the deficient rats. Increased dietary Se provided for both faster elevation, and higher maximal GSH-Px activity which in all cases was achieved 60 to 90 days after resupplementation. The results suggest that tissue GSH-Px can be used as an indicator of animal Se status, but other factors such as age, sex, and dietary vitamin E may have to be considered. Lack of GSH-Px in livers of Se-deficient rats may explain the liver necrosis observed when the diet is also deficient in vitamin E and sulfur-containing amino acids. J. Nutr. 104: 580-587,

B M Kelly

Papers

Improved method for the determination of blood glutathione.