Selenium reduces hemoglobin-induced epithelial damage to intestinal mucosa

Abstract

Modified hemoglobins are being considered as possible "blood substitutes." Experiments were performed to determine whether diaspirin cross-linked hemoglobin (DBBF-Hb) produces epithelial damage and whether this is reduced by selenium (Se). Anesthetized Sprague-Dawley rats, half of which received 2×10-6 g/ml Se, daily for 3 weeks, in their drinking water, were injected with a 5 ml bolus of 10 mg/ml DBBF-Hb. Control animals received saline (5 animals per group). After 30 minutes, the intestine was perfusion-fixed for light and electron microscopy. Eighty villi per rat were assigned an epithelial integrity index (E.I.), ranging from 1 (intact) to 3 (some cell-cell and cell-basement membrane separation). In non-Se rats, E.I. was significantly compromised by DBBF-Hb, compared to HBSBSA (2.47±0.57 (SD) vs. 1.36±0.49, p<0.001). In Se rats, neither injection with DBBF-Hb or HBS-BSA caused epithelial damage (1.03±0.17 vs. 1.07±0.26). Mast cell degranulation per villus (MCD) was measured in 60 villi per rat. In non-Se rats, MCD was significantly greater after DBBF-Hb than after HBS-BSA injection (1.83±1.42 vs. 0.2±0.4). Supplementary Se did not reduce this effect. In fact, MCD was significantly increased in both sets of rats compared to their non-Se counterparts (3.27±2.40 and 1.48±1.70 for DBBF-Hb and HBS-BSA, respectively). Since mast cell mediators damage cells, Se must protect the mucosal epithelium in some way.