BCNU-induced protection from hyperbaric hyperoxia: role of glutathione metabolism.
To explore the role of the glutathione oxidation-reduction cycle in altering the sensitivity of rats to the effects of hyperbaric hyperoxia, we administered N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) to decrease tissue glutathione reductase activity. We then exposed these animals and their matched vehicle-treated controls to 100% O2 at 4 ATA. Animals that received BCNU and were immediately exposed to hyperbaric O2 showed enhanced toxicity by seizing earlier in the exposure than controls. Animals that received BCNU 18 h before the hyperbaric O2 exposure were paradoxically protected from the effects of the exposure with a prolongation of their time to initial seizure and a marked increase in their survival time during the exposure. Tissue glutathione concentrations were also measured in the various groups and the hyperbaric O2 exposure produced marked decreases in hepatic glutathione levels in all control animals. In animals treated with BCNU 18 h before exposure, hepatic glutathione concentrations also decreased, but the concentrations had significantly increased during the 18-h waiting period, allowing these animals to maintain hepatic levels in the normal range even during their hyperbaric exposures. We conclude that treatment of rats with BCNU 18 h before exposure to hyperbaric hyperoxia results in enhanced protection of the animals during the exposure.
Jenkinson
S G
SG
Department of Medicine, University of Texas Health Science Center, San Antonio.
Jordan
J M
JM
Lawrence
R A
RA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002330:Carmustine / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010100:Oxygen; D051381:Rats; D011919:Rats, Inbred Strains
D005978:Glutathione; D010100:Oxygen; D002330:Carmustine; D019803:Glutathione Disulfide