Prevention of hyperoxic-induced depression of pulmonary serotonin clearance by pretreatment with superoxide dismutase.

Abstract

The therapeutic usefulness of O2 is limited primarily by pulmonary O2 toxicity, and there are no effective therapeutic modalities other than avoidance for prevention of this toxicity. In the present study, superoxide dismutase, an enzyme that catalyzes the dismutation of superoxide anion to less toxic forms, as well as reduced glutathione and succinate, two agents that protect against central nervous system O2 toxicity, were evaluated for ability to protect against the development of pulmonary O2 toxicity in the rat. Pulmonary O2 toxicity was evaluated by measuring lung clearance of serotonin in the isolated, perfused lung. Depression of serotonin clearance has recently been shown to be an index of early lung O2 poisoning. Rats received 60 nmole of superoxide dismutase per kg of body weight, 16 mmole of reduced glutathione per kg, 12 mmole of succinate per kg, or an equal volume of normal saline in a single intraperitoneal injection 45 min before a 60-min exposure to either 100 per cent O2 at 4 atm absolu...