Effect of nordihydroguaiaretic acid and ibuprofen on bleomycin and hyperoxia-induced changes in lung superoxide dismutase, prostaglandins and lethality.
Mortality in hamsters injected intratracheally with bleomycin (bleo) (0.25 units) and exposed to 70% oxygen is significantly increased over 14 days when they receive nordihydroguaiaretic acid (NDGA, 10 mg/kg per day S.C.). Mortality in bleo +O2 challenged hamsters treated with ibuprofen (10 mg/kg per day) subcutaneously was not significantly increased. The increased mortality in NDGA treated animals is not the result of augmented superoxide formation, since no change in lung superoxide dismutase occurred. Among the prostaglandins measured, NDGA produced the greatest elevation in 6-keto-PGF1 alpha (stable product of prostacyclin) and thromboxane B2 (stable product of thromboxane A2).
Giri
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SN
Department of Molecular BioSciences, University of California, Davis 95616, USA.
Hollinger
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MA
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D001761:Bleomycin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D018496:Hyperoxia / Q000201:enzymology / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology*; D007442:Intubation, Intratracheal; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D008647:Mesocricetus; D011453:Prostaglandins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D017382:Reactive Oxygen Species; D001761:Bleomycin; D009637:Masoprocol; D013482:Superoxide Dismutase; D007052:Ibuprofen