Exogenous glutathione can increase glutathione levels in tissues of rainbow trout (Oncorhynchus mykiss) through extracellular breakdown and intracellular synthesis

Glutathione (GSH) is an important intracellular antioxidant involved in numerous cellular pathways. However, little is known about the transport of GSH into fish tissues. To determine whether fish tissues took up GSH by extracellular breakdown and intracellular synthesis or by direct cellular transport, we injected rainbow trout (Oncorhynchus mykiss) with exogenous GSH along with blockers of GSH breakdown and synthesis. Exogenous GSH increased GSH levels to the greatest degree in the cells of the posterior kidney, followed by the liver. Exogenous GSH inconsistently increased liver GSH levels independent of GSH synthesis, although this may have been due to disruption of gradient-dependent GSH export, and not necessarily to intact uptake of GSH. The cells of the posterior kidney, liver and gill took up GSH by extracellular breakdown and intracellular synthesis. This indicates that, unlike mammalian tissues, normal cellular GSH levels in fish are not sufficient to inhibit additional GSH synthesis. This may lend flexibility to the GSH system in fish, where levels of GSH may rapidly increase in response to an increased supply of amino acids, or during times of high demand, without increasing synthesis enzymes.