The American journal of physiology
-
Rats exposed to hyperbaric hyperoxia experience severe central nervous system and lung toxicity. Exogenous glutathione administration has been shown to protect rats from the effects of hyperbaric hyperoxia. To explore the hypothesis that decreases in tissue glutathione (GSH) could increase the susceptibility of rats to hyperbaric hyperoxia, we administered diethyl maleate (DEM) (a compound that conjugates with GSH and rapidly lowers tissue levels) and measured tissue GSH levels. ⋯ Rats that received DEM 2 h before exposure seized earlier and died earlier than controls. Intraperitoneal administration of GSH to DEM-treated rats abolished the enhanced toxicity occurring during a hyperbaric hyperoxic exposure. DEM appears to increase the toxicity of rats exposed to hyperbaric hyperoxia by lowering tissue GSH levels, and replenishment of lung and brain GSH by exogenous administration reverses these effects.