Antioxidants attenuate endotoxin-induced microvascular leakage of macromolecules in vivo.
The purpose of this study was to examine whether antioxidants attenuate endotoxin-induced microvascular hyper-permeability for macromolecules in the hamster cheek pouch. Twenty-two adult male Syrian hamsters were anesthetized, and a removable plastic chamber was placed in the cheek pouch to observe and collect suffusate from the microvasculature. Fluorescent-labeled dextran (FITC-D; mol wt 150,000) was injected intravenously, and changes in the number of microvascular leaky sites and microvascular clearance of FITC-D were measured in five groups: saline control (group 1, n = 4), endotoxin (0.1 mg/ml) suffusion for 120 min (group 2, n = 6), endotoxin plus dimethyl sulfoxide (1.0 g/kg iv; group 3, n = 4), endotoxin plus allopurinol (30 mg/kg ip; group 4, n = 4), and endotoxin plus dimethyl sulfoxide and allopurinol (group 5, n = 4). The number of leaky sites and the FITC-D clearance were significantly higher in group 2 [45 +/- 18 (SD) sites/cm2 and 20 +/- 6 X 10(-6) ml/min, respectively; P less than 0.01] than in group 1 (7 +/- 6 sites/cm2 and 7 +/- 5 X 10(-6) ml/min), group 3 (9 +/- 5 sites/cm2 and 8 +/- 2 X 10(-6) ml/min), group 4 (11 +/- 7 sites/cm2 and 9 +/- 4 X 10(-6) ml/min), and group 5 (11 +/- 6 sites/cm2 and 7 +/- 1 x 10(-6) ml/min). The leaky sites appeared predominantly in postcapillary venules. There was a positive and significant correlation between the number of leaky sites and FITC-D clearance.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsuda
T
T
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-2465.
Eccleston
C A
CA
Rubinstein
I
I
Rennard
S I
SI
Joyner
W L
WL
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D006224:Cricetinae; D003911:Dextrans; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins; D005609:Free Radicals; D008297:Male; D008647:Mesocricetus; D010100:Oxygen / Q000378:metabolism
D000975:Antioxidants; D003911:Dextrans; D004731:Endotoxins; D005452:Fluoresceins; D005609:Free Radicals; C015219:fluorescein isothiocyanate dextran; D000493:Allopurinol; D016650:Fluorescein-5-isothiocyanate; D010100:Oxygen; D004121:Dimethyl Sulfoxide