IMPACT OF DIETARY PROTEIN ON BRAIN GLUTATHIONE IN STROKE

In the present study, we proposed that dietary protein deficiency would depress brain glutathione (GSH) concentration. If the hypothesis were correct, this would suggest compromised antioxidant defense in stroke patients with poor protein status. The effect of L-2-oxothiazolidine-4-carboxylate (OTC), a precursor of the limiting amino acid (cysteine) for intracellular GSH synthesis, was also investigated in this study. Male Long-Evans weanling rats were randomly assigned to one of three experimental groups fed: 1) a protein-deficient diet modified from the AIN-93G diet containing 7.5% protein, 2) the OTC-supplemented diet containing 7.5% protein and supplemented with 0.453% OTC to be equivalent in sulfur content with that in the protein-adequate diet, and 3) the protein-adequate (control) diet containing 17.9% protein. After 6 weeks of feeding, the liver, neocortex, striatum, hippocampus, thalamus, cerebellum, and brain stem were collected for analysis of GSH concentration by reverse-phase high performance liquid chromatography (HPLC). This method used precolumn derivatization with 5, 5'-dinitrobis (2-nitrobenzoic acid) (DTNB) and ultraviolet detection at 330 nm. Hepatic GSH concentration was significantly decreased by protein deficiency. OTC supplementation of protein-deficient rats increased hepatic GSH concentration to a near normal level. GSH concentration in various brain regions was not significantly lower in rats fed a protein-deficient diet than that fed the normal diet. OTC supplementation increased neocortical GSH concentration over that of the protein-deficient rats. These results suggest that brain GSH concentration was well maintained during moderate protein deficiency. This is probably due to sustained capacity of GSH synthesis, uptake mechanisms of GSH, and transport systems of sulfur amino acids to the brain when dietary protein intake is moderately low. Also, 11OTC supplementation elevated cysteine concentration in the neocortex and cerebellum of the protein-deficient rats, suggesting that OTC is an effective vehicle for delivering cysteine and may provide a therapeutic intervention for stroke patients with depleted brain GSH