Elimination of glutathione-induced protection from hyperbaric hyperoxia by acivicin

M. D. Peacock, D. A. Schenk, R. A. Lawrence, J. A. Morgan, S. G. Jenkinson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Glutathione (GSH) administered intraperitoneally significantly prolongs the time to initial seizure and survival time of rats exposed to hyperbaric hyperoxia (HBO). Acivicin is an antitumor antibiotic that is an inhibitor of γ-glutamyl transpeptidase (GGT), an enzyme necessary for the breakdown and transport across cell membranes of GSH. To determine whether acivicin treatment alters GSH-induced protection from HBO, rats were dosed with 25 mg/kg of acivicin or vehicle 1 h before O2 exposure at an inspired O2 fraction of 1.0 at 4 ATA. Immediately before exposure, rats received GSH (1 mmol/kg) or vehicle. Time to seizure and time to death were recorded during exposure by direct observation. In separate groups of rats on the same dosing schedule, plasma GSH, renal GGT, and brain GGT were measured 15 min after the GSH injection without HBO exposure and 100 min after the beginning of HBO exposure. Renal GGT was decreased to 2.5% of control and brain GGT to 37% of control in the acivicin-dosed rats. Plasma GSH increased 3-fold in rats given acivicin alone, 52-fold in rats given GSH alone, and 84-fold in rats receiving both acivicin and GSH. Rats dosed with GSH alone had significantly prolonged times to seizure and death compared with all other groups. Rats dosed with GSH after receiving acivicin were not protected from HBO despite the large increase in plasma GSH that occurred in these animals. GSH treatment did not increase tissue GSH in lung, liver, or brain at 160 or 200 min of exposure. These data support the hypothesis that acivicin treatment abolishes GSH-induced protection from HBO and that elevations in plasma GSH do not protect acivicin-treated animals.

Original languageEnglish (US)
Pages (from-to)1279-1284
Number of pages6
JournalJournal of applied physiology
Issue number3
StatePublished - 1994
Externally publishedYes


  • hyperbaric oxygen toxicity
  • rat
  • γ-glutamyl transpeptidase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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