Protection from hyperbaric oxidant stress by administration of buthionine sulfoximine.
To explore the role of glutathione in protecting rats from hyperbaric hyperoxia, we administered buthionine sulfoximine (BSO) to block gamma-glutamyl cysteine synthase activity and decrease tissue glutathione synthesis. We then exposed these animals and their vehicle-treated matched controls to 100% oxygen at 4 ATA or room air at 1 ATA. After BSO treatment, glutathione concentrations in air-exposed controls decreased 62% in lung, 76% in liver, 28% in brain, and 62% in plasma. Paradoxically, BSO-treated rats were protected from hyperbaric hyperoxia. The BSO-treated animals seized significantly later and had a markedly prolonged time of survival compared with the vehicle-treated controls. We conclude that BSO treatment protects rats from hyperbaric hyperoxia, despite its effects of lowering plasma and tissue glutathione concentrations. This protection may be related to a direct effect of the compound in decreasing free radical-mediated tissue injury, increasing tissue antioxidant defenses, or increasing seizure threshold.
Lung Metabolic Unit, University of Texas Health Science Center, San Antonio.
K H
KH
Komadina
C A
CA
Duncan
C L
CL
Bryan
S G
SG
Jenkinson
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D019328:Buthionine Sulfoximine; D004032:Diet; D005609:Free Radicals; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000096:biosynthesis; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013858:Thiobarbiturates
D000963:Antimetabolites; D005609:Free Radicals; D013858:Thiobarbiturates; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D010100:Oxygen