title: Extracellular fetal hemoglobin induces increases in glomerular permeability: inhibition with α1-microglobulin and tempol.
abstract: Extracellular fetal hemoglobin (HbF) and adult hemoglobin (HbA) are proinflammatory and generate ROS. Increased plasma levels of extracellular HbF have recently been reported to occur in early preeclampsia. α1-Microglobulin (A1M) is a physiological heme-binding protein and radical scavenger that has been shown to counteract vascular permeability increases induced by HbA in the perfused placenta. The present study was performed to investigate whether HbF and HbA will increase glomerular permeability in vivo and to test whether A1M and tempol, a ROS scavenger, can prevent their effects. Anesthetized Wistar rats were continuously infused intravenously with either HbA, HbF, or cyano-inactivated HbF together with FITC-Ficoll-70/400, inulin, and (51)Cr-labeled EDTA for 2 h. Plasma samples and urine samples (left ureter) were taken repeatedly and analyzed by high-performance size exclusion chromatography to assess glomerular sieving coefficients for Ficoll of radius 10-80 Å. In separate experiments, A1M or tempol was given before and during Hb infusions. Extracellular HbF caused rapid, transient increases in glomerular permeability to large Ficoll molecules (50-80Å), contrary to the effects of HbA and cyano-inactivated HbF. For HbF, glomerular sieving coefficients for Ficoll of radius 60Å increased from 3.85 ± 0.85 × 10(-5) to 2.60 ± 0.96 × 10(-4) at 15 min, changes that were abrogated by tempol and reduced by A1M. In conclusion, our data demonstrate that extracellular HbF, infused systemically, can acutely increase glomerular permeability through inducing oxidative stress.
authors: Dept. of Nephrology, Lund Univ., Skåne Univ. Hospital, Lund S-211 85, Sweden. Bengt.Rippe@med.lu.se.
authors: Kristinn
authors: K
authors: Sverrisson
authors: Josefin
authors: J
authors: Axelsson
authors: Anna
authors: A
authors: Rippe
authors: Magnus
authors: M
authors: Gram
authors: Bo
authors: B
authors: Åkerström
authors: Stefan R
authors: SR
authors: Hansson
authors: Bengt
authors: B
authors: Rippe
mesh_terms: D000510:Alpha-Globulins / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005319:Fetal Hemoglobin / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels
chemical_list: D000510:Alpha-Globulins; D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; C025734:chorionic alpha(1)-microglobulin; D005319:Fetal Hemoglobin; C001803:tempol
keywords: Ficoll; adult hemoglobin; capillary permeability; glomerular sieving coefficient; preeclampsia