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.