Catalase prevents prostanoid release and lung lipid peroxidation after endotoxemia in sheep.
We determined the effect of H2O2 on both the physiological and biochemical lung changes seen in the adult sheep after endotoxin. Fourteen unanesthetized adult sheep with chronic lung lymph fistula were given Escherichia coli endotoxin (1 microgram/kg) over 30 min. Seven sheep were given catalase (32,500 U/kg body wt) as an intravenous bolus 30 min before endotoxin. Four sheep were given catalase alone. Oxidant lung changes were measured using arterial plasma conjugated dienes and lung tissue malondialdehyde (MDA) content, both reflecting the lipid peroxidation process. Animals were killed 5 h after endotoxin. We found that endotoxin alone caused an early increase in pulmonary arterial pressure lung lymph flow (QL), plasma thromboxane B2, 6-keto-prostaglandin F1 alpha, and plasma conjugated dienes. A decrease in cardiac output and arterial PO2 was also seen. A three- to four-fold increase in protein-rich QL was noted at 3-4 h as well as a continued increase in arterial conjugated dienes. Lung MDA and water content were also significantly increased from base line. Catalase pretreatment significantly attenuated both the physiological changes and the prostanoid and conjugated diene release. Lung MDA and water content also remained at base line. We conclude that H2O2 plays a major role in endotoxin-induced lung injury as well as the resulting lipid peroxidation process.
Seekamp
A
A
Longwood Area Trauma Center, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Lalonde
C
C
Zhu
D G
DG
Demling
R
R
D000818:Animals; D002374:Catalase / Q000494:pharmacology*; D004731:Endotoxins / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D012756:Sheep; D013928:Thromboxane A2 / Q000378:metabolism; D014115:Toxemia / Q000188:drug therapy / Q000503:physiopathology*
D004731:Endotoxins; D008054:Lipid Peroxides; D011453:Prostaglandins; D013928:Thromboxane A2; D006861:Hydrogen Peroxide; D002374:Catalase