Rogers JM, Hunter ES III. 2001. Toxicological highlight. Redox redux: A closer look at conceptual low molecular weight thiols. Toxicol Sci 62:1–3.
Glutathione (GSH) is present as the most abundant low molecular weight thiol (LMWT) in virtually all mitochondria-bearing eucaryotic cells, often at millimolar concentrations (Meister, 1988). Functions of GSH include roles in DNA and protein synthesis, maintenance of cell membrane integrity, drug and chemical metabolism, and protection from oxidative stress. The role of GSH in normal reproduction and development, as well as its role in protecting against reproductive toxicants, has been studied extensively, but remains poorly understood. Sources of reducing equivalents other than GSH provide unique as well as redundant functions and include the thioredoxin pathway, superoxide dismutase, catalase, and cysteine. The presence of functional redundancy, as well as the ability of many mammalian cells to tolerate substantial decreases in intracellular GSH, has made studies of the specific roles of glutathione in reproductive and developmental toxicity difficult, and results have been discordant. In the feature article, Beck et al. take a novel and important approach to studying the content and distribution of GSH and cysteine in organogenesis-stage embryos, using acetaminophen (APAP) as a modulator of GSH and mercury orange staining to localize LMWT. Their results provide insight on the redox status and capacity of these embryos, including compartmentalization and intracellular distribution.