The effects of glutathione glycoside in methyl mercury poisoning

The use of glutathione glycoside (GSH-glyc), a compound newly synthesized in our laboratory, was highly effective in raising cellular GSH levels both in vitro and in vivo. Based on mass spectrometry and 1H NMR data, the structure of GSH-glyc was determined to be that of an S-glycoside. Rapid GSH uptake was observed by confocal microscopy in both A549 cells and mouse astrocytes following incubation with GSH-glyc. Intraperitoneal (i.p.) and per oral administration of GSH-glyc in C57BL/6J mice raised GSH concentrations in brain and liver to significantly higher levels than normal. Methyl mercury (MeHg) poisoning of mice with multiple doses of methylmercuric chloride (MMC) induced severe toxic effects associated with marked depletion of brain and liver GSH progressing to death in all animals, whereas the animals primed with GSH-glyc and given MMC and GSH-glyc concurrently were devoid of toxic signs. We suggest, on the basis of D-[3H]glucose and [2- 3H]deoxyglucose uptake studies, that the transport of GSH-glyc across the blood-brain barrier may occur through one of the glucose transport pathways. Although the precise mechanism by which GSH-glyc protects against MeHg poisoning is not clear, it is probable that any one of a number of factors, including conjugation of MeHg, scavenging of free radicals, restoration of reactive thiol groups, and enhancement of MeHg efflux, may have been instrumental. GSH-glyc is a nontoxic compound that can be used to transport GSH into cells, including those of brain and liver, and may prove to be useful for prophylaxis and therapy of tissue injury induced by various neurotoxic compounds, particularly when the capacity to synthesize or regenerate GSH has been compromised.