Transitional vacuole formation following a bolus infusion of PEG-hemoglobin in the rat.
This study was designed to assess the morphological effects of a bolus infusion of PEG-hemoglobin on the heart, lung, liver, spleen and kidney of laboratory rats. Of particular interest was the determination of PEG-hemoglobin's potential to form vacuoles in the tissues and whether these were transitory and article specific. One hundred ten female Sprague-Dawley rats were used in this study. The first experiment determined whether vacuole formation was test article specific by infusing either stroma-free bovine hemoglobin, PEG-hemoglobin, bovine serum albumin, PEG-bovine serum albumin or free PEG. The second experiment assessed the transitory nature of vacuolization. In both experiments, unconscious rats received an intravenous top-loading (bolus) injection of test article via the tail vein. Rats were sacrificed at various time points following administration and had their tissues examined for the presence of vacuoles by light microscope morphological examination and iron staining. Formation of vacuoles appeared to be test article specific with only prolonged circulating, high solute test articles producing vacuoles. These vacuoles appeared dose responsive and transitory in nature. The vacuolization found was non-toxic and believed to be due to the known effect of lysosomal overloading following the phagocytosis of vascularly persistent high solute test articles.
Conover
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Research and Development Formulations-Toxicology Department, Enzon Inc., Piscataway, NJ 08854, USA.
Lejeune
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Linberg
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Shum
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Shorr
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RG
D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects / Q000648:ultrastructure; D009206:Myocardium / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000648:ultrastructure; D014617:Vacuoles
D006454:Hemoglobins; D011092:Polyethylene Glycols