Sodium selenite reduces hemoglobin-induced venular leakage in the rat mesentery

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Abstract
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 (Na2SeO3) was used in an attempt to reduce leak formation. In anesthetized Sprague-Dawley rats, one-half of which received 2 × 10−6g/ml Na2SeO3in 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, Na2SeO3significantly reduced leak number, leak area, and mast cell degranulation. Venular leakage was also reduced in rats that only received Na2SeO3locally during DBBF-Hb perfusion. However, Na2SeO3did 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, Na2SeO3reduced the oxidation rate of DBBF-Hb while in the presence of oxidants. These results suggest that Na2SeO3reduces DBBF-Hb-induced microvascular leakage partly by retarding the oxidation of its heme iron.

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