Apparent first-order rate constants for glutathione (GSH) turnover were determined for 14 tissues in male Fischer 344 rats after intravenous injection of [35S]cysteine ([35S]Cys). Rate constants for glutathione turnover were estimated by nonlinear least-squares iterative minimization from the decrease in GSH specific activity 1-102 hr after administration of [35S]Cys. Tissue nonprotein sulfhydryl concentrations were determined by Ellman′s assay and compared with GSH and Cys levels detected by high-performance liquid chromatography equipped with an electrochemical detector. Additionally, total radiolabeled [35S]-GSH was determined by high-performance liquid chromatography equipped with a flow-through radioactivity detector. There were substantial differences in the apparent rates of GSH turnover between the various tissues examined. For example, both the liver and the kidney had rapid turnover rates with half-lives of 1-5 hr, while those for heart, skeletal muscle, and blood were much slower with half-lives of 68-118 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach caecum > duodenum = small intestine = large intestine > colon > forestomach. [35S]-GSH had a half-life in lung and skin of approximately 63 and 50 hr, respectively.
