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- W2022174633 endingPage "469" @default.
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- W2022174633 abstract "Hb (haemoglobin)-based blood substitutes represent a class of therapeutics designed to correct oxygen deficit under conditions of anaemia and traumatic blood loss. The influences of these agents on HIF-1alpha (hypoxia-inducible factor-1alpha) target genes involved in adaptation to hypoxia have so far not been studied. In the study presented here, rats underwent 80% ET (exchange transfusion) with either HS (hetastarch) or a polymerized Hb OG (Oxyglobin). HS induced dramatic EPO (erythropoietin) gene transcription, reaching a maximum at 4 h post-ET. In contrast, OG suppressed EPO transcription until approx. 24 h post-ET. Large plasma EPO levels that were observed post-ET with HS were significantly blunted in animals transfused with OG. OG, unlike HS, induced a sharp increase in HO-1 (haem oxygenase-1) transcription at 4 h, which declined rapidly within 24 h, whereas modest increases in iNOS [inducible (nitric oxide synthase)] and constitutive NOS [eNOS (endothelial NOS)] were detected over the control. Our results demonstrate for the first time that severe haemodilution-induced erythropoietic responses in kidneys were attenuated by a low-oxygen-affinity cell-free Hb and suggest that tissue-specific oxygen-sensing pathways can be influenced by allosterically modified Hbs." @default.
- W2022174633 created "2016-06-24" @default.
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- W2022174633 date "2008-08-27" @default.
- W2022174633 modified "2023-09-23" @default.
- W2022174633 title "Acellular haemoglobin attenuates hypoxia-inducible factor-1α (HIF-1α) and its target genes in haemodiluted rats" @default.
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- W2022174633 doi "https://doi.org/10.1042/bj20080313" @default.
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