Influence of rat brain superoxide dismutase inhibition by diethyldithiocarbamate upon the rate of development of central nervous system oxygen toxicity.
Exposure to oxygen at pressures greater than 2.8 ATA (OHP) results in central nervous system toxicity seen as grand mal seizures. The time to onset of seizures (ts) is related to the pO2 above the 2.8 ATA threshold. The components of the endogenous antioxidant defense mechanism, superoxide dismutase (SOD), glutathione measured here as nonprotein sulfhydryl content (NPSH), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR), and glutathione peroxidase (GPx) occur in brain. Their role in OHP-induced CNS toxicity is not clear. This study examined the effect of inhibition of SOD by diethyldithiocarbamate (DDC) on ts at 4 ATA O2. Antioxidant components (SOD, NPSH, G-6-PD, GR, and GPx) were measured in male Sprague-Dawley rats pretreated with 250, 500, and 1000 mg/kg DDC ip, 2 hr prior to termination in room air. SOD activity was inhibited 11, 31, and 49%, respectively, when compared with control values. Among the other antioxidant components, only GPx showed a significant loss of activity of 24% at 1000 mg/kg DDC. Rats were also pretreated 2 hr prior to exposure to hyperbaric oxygen with either 250, 500, or 1000 mg/kg DDC. Ts for the treated animals was significantly shortened by 12, 55, and 75%, respectively, compared to the saline-treated, oxygen-exposed control animals. These studies demonstrated that the rate of onset of CNS oxygen toxicity was increased by inhibition of SOD by DDC. These data suggested that SOD plays a role as part of an endogenous antioxidant defense mechanism in the brain.
D000818:Animals; D001274:Atmospheric Pressure; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004050:Ditiocarb / Q000494:pharmacology*; D004347:Drug Interactions; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D013859:Thiocarbamates / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D013859:Thiocarbamates; D004050:Ditiocarb; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D010100:Oxygen