The influence of polyethylene glycol conjugation on bovine hemoglobin's intrinsic effect on the gastrointestinal system of the rat.
The purpose of this study was to determine the impact of polyethylene glycol (PEG) conjugation on bovine hemoglobin's effect on gastrointestinal (GI) blood flow and motility in the Sprague Dawley rat. This study was divided into two parts: part one assessed blood flow, while the other evaluated bolus transit time through the GI. To examine blood flow, thirty-two rats were divided into four experimental groups (PEG-hemoglobin, bovine hemoglobin, Ringer's Lactate and autologous blood sham). Blood flow within the superior mesenteric artery was monitored during graduated isovolemic hemodilution. In the second part of the study, GI motility was estimated by bolus transit time. Thirty-six rats were assigned to four groups (PEG-hemoglobin, bovine hemoglobin, Ringer's Lactate and no treatment sham) and following an overnight fast, the rats were given a bolus injection (25 mL/kg) of test article. Three hours following injection, they received an oral 0.3 mL gavage of a charcoal/arabic gum mixture and were later sacrificed and their GI tract evaluated. Results indicated that the infusion of bovine hemoglobin reduced both baseline blood flow through the mesenteric artery and gastrointestinal transit time. In contrast, PEG-hemoglobin maintained baseline blood flow through the mesenteric artery and had no effect on GI transit time or morphology. Therefore, PEG conjugation of bovine hemoglobin significantly attenuated its intrinsic effect on the GI system of the rat.
Conover
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Formulations-Toxicology Department, Enzon Incorporated, Piscataway, New Jersey 08854, USA.
Lejeune
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Shum
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Shorr
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D000818:Animals; D002417:Cattle; D004064:Digestive System / Q000098:blood supply / Q000187:drug effects*; D005772:Gastrointestinal Transit; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology*; D008638:Mesenteric Arteries; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
D006454:Hemoglobins; D011092:Polyethylene Glycols