Elevation of lung glutathione by oral supplementation of L-2-oxothiazolidine-4-carboxylate protects against oxygen toxicity in protein-energy malnourished rats.

The objectives of this study were to investigate whether oral supplementation of L-2-oxothiazolidine-4-carboxylate (OTC) is effective for increasing tissue glutathione (GSH) concentrations in rats fed a diet very low (0.5%) in protein-a model of wasting malnutrition-and to determine the efficacy of OTC for protection against pulmonary oxygen toxicity. Weanling rats, fed a 0.5 or 15% protein diet for 2 wk, were given an oral supplement of OTC, and tissue GSH concentrations were measured over a 24 h period. OTC supplementation to rats fed 0.5% protein significantly increased GSH concentrations in liver and lung, but not in kidney and blood, when compared with the 0.5% protein unsupplemented group. The liver GSH concentration in the 0.5% protein OTC-supplemented group was higher than the 15% control group. Daily supplementation of OTC protected rats from pulmonary oxygen toxicity during 4 days of 85% oxygen exposure as determined by lung-to-body weight ratios and in vivo proton magnetic resonance imaging. Although hyperoxia exposure increased lung GSH concentrations in all groups, OTC supplementation was effective for increasing lung GSH concentration in rats fed the 0.5% protein diet. This study demonstrated that oral administration of OTC to wasting malnourished rats is an effective procedure to increase GSH concentration rapidly in target organs such as lung, and that daily supplementation of a low dose of OTC has a sustained effect to protect against pulmonary oxygen toxicity during 4 days of hyperoxia exposure.

Effect of dietary protein deficiency and L-2-oxothiazolidine-4-carboxylate on the diurnal rhythm of hepatic glutathione in the rat.

Maximizing hepatic glutathione (GSH) concentration may provide greater protection against toxic compounds. A dietary supplement of L-2-oxothiazolidine-4-carboxylate (OTC), a stable derivative of cysteine, increased hepatic GSH in rats fed for 2 wk a diet deficient in protein (7.5%) but not in rats fed a diet adequate in protein (15%). Experiment 2 determined whether a dietary supplement of OTC could maintain the maximum GSH concentration over 24 h. Rats acclimatized for 5 d to a 7.5% protein diet and then fed a 7.5% protein diet supplemented with either 2.5 mmol OTC or cysteine-HCl (CYS)/100 g diet had a more rapid increase in hepatic GSH (4 and 8 h after beginning of feeding, P less than 0.05) than did rats fed an unsupplemented 7.5% protein diet. This response was not due simply to the greater supply of cysteine for GSH synthesis because supplementing the 15% protein diet with OTC or CYS had no effect on the hepatic GSH of rats acclimatized to a 15% protein diet. In experiment 3, rats acclimatized to the 7.5% protein diet had a more rapid rate of increase in hepatic GSH concentration in response to feeding than did rats acclimatized to a 15% protein diet, regardless of which diet they were fed during the 24-h period. It was concluded that in addition to cysteine availability, previous dietary protein status plays a key role in the regulation of the feeding-induced diurnal rhythm of hepatic GSH concentration in rats.