Pretreatment with catalase or dimethyl sulfoxide protects alloxan-induced acute lung edema in dogs.
We tested the preventive effects of catalase, an enzymatic scavenger of hydrogen peroxide, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, on intravenous alloxan-induced lung edema in four groups of pentobarbital sodium-anesthetized, ventilated dogs for 3 h: saline (20 ml.kg-1.h-1) infusion alone (n = 5), alloxan (75 mg/kg) + saline infusion (n = 5), catalase (150,000 U/kg) + alloxan + saline infusion (n = 5), or DMSO (4 mg/kg) + alloxan + saline infusion (n = 5). Catalase or DMSO significantly prevented the increase in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha over 3 h after alloxan and the accumulation of extravascular lung water after 3 h [3.95 +/- 0.52 (SE) g/g with catalase, 3.06 +/- 0.42 g/g with DMSO] but not early pulmonary arterial pressor response. An electron microscopic study indicated that catalase or DMSO significantly reduced the endothelial cellular damages after alloxan. These findings strongly suggest that hydrogen peroxide and hydroxyl radical are major mediators responsible for intravenous alloxan-induced edematous lung injury in anesthetized ventilated dogs.
Kawada
T
T
Second Department of Internal Medicine, Gifu University School of Medicine, Japan.
Kambara
K
K
Arakawa
M
M
Segawa
T
T
Ando
F
F
Hirakawa
S
S
Emura
S
S
Shoumura
S
S
Isono
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000208:Acute Disease; D000496:Alloxan / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004285:Dogs; D004727:Endothelium / Q000473:pathology; D016166:Free Radical Scavengers; D005609:Free Radicals; D007958:Leukocyte Count; D008854:Microscopy, Electron; D010976:Platelet Count; D011650:Pulmonary Alveoli / Q000473:pathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011669:Pulmonary Wedge Pressure; D013929:Thromboxane B2 / Q000494:pharmacology
D016166:Free Radical Scavengers; D005609:Free Radicals; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000496:Alloxan; D002374:Catalase; D004121:Dimethyl Sulfoxide