Isolated perfused lung histamine release, lipid peroxidation, and tissue superoxide dismutase from rats exposed to normobaric hyperoxia.
Female Sprague-Dawley inbred rats were exposed to either 1 atm of 100% O2 for 24 h, or 65% O2 for 5 days, with or without pretreatment with disulfiram, an inhibitor of lung CuZn-SOD. After O2 exposure, the rats were killed, the lungs removed, and isolated perfused lungs (IPLs) prepared. The IPLs were perfused with modified Krebs-Henseleit buffer, and perfusate histamine, malondialdehyde (MDA), and lung tissue CuZn-SOD activity examined. Disulfiram administration decreased the LT50 of O2-exposed rats from 65 to 36 h. Histamine and MDA in the perfusate from the IPL prepared from rats exposed to 100% O2 for 24 h were markedly increased. When rats were pretreated with disulfiram and exposed to 100% O2 for 24 h, histamine and MDA were increased an additional 77% and 45%, respectively. In separate experiments, 100% O2 exposure significantly decreased lung CuZn-SOD activity by 40% while IPL histamine and MDA were significantly increased. However, exposure of rats to 65% O2 for 5 days decreased lung CuZn-SOD by 69% but did not affect IPL histamine release or perfusate MDA. These studies suggest that IPL histamine release and/or MDA may be an early biochemical marker for pulmonary O2 toxicity, that lung CuZn-SOD activity may not be the only determinant in O2 toxicity, and other defense mechanisms may play a vital protective role during sublethal O2 exposures.
D000818:Animals; D001273:Atmosphere Exposure Chambers; D004221:Disulfiram / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006632:Histamine / Q000032:analysis / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008314:Malonates / Q000378:metabolism*; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism*; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism*
D008314:Malonates; D008315:Malondialdehyde; D006632:Histamine; D013482:Superoxide Dismutase; D010100:Oxygen; D004221:Disulfiram