Sodium selenite reduces hemoglobin-induced venular leakage in the rat mesentery.
Modified Hbs are being developed as "blood substitutes," but intravascular injection of diaspirin cross-linked Hb (DBBF-Hb) can produce venular leakage. Hb toxicity may arise from reactive oxygen species, so the antioxidant sodium selenite (Na(2)SeO(3)) was used in an attempt to reduce leak formation. In anesthetized Sprague-Dawley rats, one-half of which received 2 x 10(-6) g/ml Na(2)SeO(3) in their drinking water for 3 wk, the mesenteric microvasculature was perfused with 2 mg/ml DBBF-Hb (N = 8) for 10 min. Controls (N = 7) received saline. This was followed by perfusion with FITC-albumin for 3 min, fixation, and microscopic examination. In rats given DBBF-Hb, Na(2)SeO(3) significantly reduced leak number, leak area, and mast cell degranulation. Venular leakage was also reduced in rats that only received Na(2)SeO(3) locally during DBBF-Hb perfusion. However, Na(2)SeO(3) did not affect animals receiving cyanomet-DBBF-Hb instead of DBBF-Hb and significantly increased leak number and mast cell degranulation in animals receiving saline. In vitro, Na(2)SeO(3) reduced the oxidation rate of DBBF-Hb while in the presence of oxidants. These results suggest that Na(2)SeO(3) reduces DBBF-Hb-induced microvascular leakage partly by retarding the oxidation of its heme iron.
Baldwin
Ann L
AL
Department of Physiology, College of Medicine, University of Arizona, Tucson 85724-5051, USA. abaldwin@u.arizona.edu
Wiley
Elizabeth B
EB
Summers
Amber G
AG
Alayash
Abdu I
AI
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D015550:Cell Degranulation / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000502:physiology; D008706:Methemoglobin / Q000031:analogs & derivatives / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018038:Sodium Selenite / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D014699:Venules / Q000187:drug effects*
D006454:Hemoglobins; C083479:diaspirin-cross-linked cyanomethemoglobin; D008706:Methemoglobin; C083478:diaspirin-cross-linked hemoglobin; D018038:Sodium Selenite; D001241:Aspirin; D010100:Oxygen