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.