COMPARTMENTATION OF GLUTATHIONE - IMPLICATIONS FOR THE STUDY OF TOXICITY AND DISEASE

The fact that glutathione (GSH) plays many roles in biological protect ive mechanisms and critical physiological functions has been recognize d for decades, Conjugates, disulfides, and other glutathione-derived p roducts also have been studied as biomarkers of the chemical natures o r specific identities of key metabolites of toxic agents and such stud ies have been crucial in the delineation of the nature of the interact ions of proximal toxicants with target biomolecules. Despite the exten sive evidence implicating the depletion and/or oxidation of glutathion e in a wide variety of human and experimental toxicities, critical exa mination of such studies frequently reveals that injury is not simply related to glutathione status, GSH is compartmentalized at several lev els and this compartmentation appears to exert considerable influence on the relationships between glutathione depletion or oxidation and th e onset of injury, Although compartmentation is usually viewed from th e perspective of different intracellular pools, the significance of ex tracellular glutathione in functionally important pools is gaining rec ognition, As the factors affecting the interactions of intracellular p ools with extracellular pools are delineated, studies in humans can be designed and interpreted with greater precision and utility. (C) 1996 Academic Press, Inc.