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Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep
ABSTRACT: Prophylactic creatine treatment may reduce hypoxic brain injury due to its ability to sustain intracellular ATP levels thereby reducing oxidative and metabolic stress responses during oxygen deprivation. Using microdialysis, we investigated the real‐time in vivo effects of fetal creatine s...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542404/ https://www.ncbi.nlm.nih.gov/pubmed/35587817 http://dx.doi.org/10.1113/JP282840 |
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author | Tran, Nhi Thao Kowalski, Greg M. Muccini, Anna M. Nitsos, Ilias Hale, Nadia Snow, Rod J. Walker, David W. Ellery, Stacey J. |
author_facet | Tran, Nhi Thao Kowalski, Greg M. Muccini, Anna M. Nitsos, Ilias Hale, Nadia Snow, Rod J. Walker, David W. Ellery, Stacey J. |
author_sort | Tran, Nhi Thao |
collection | PubMed |
description | ABSTRACT: Prophylactic creatine treatment may reduce hypoxic brain injury due to its ability to sustain intracellular ATP levels thereby reducing oxidative and metabolic stress responses during oxygen deprivation. Using microdialysis, we investigated the real‐time in vivo effects of fetal creatine supplementation on cerebral metabolism following acute in utero hypoxia caused by umbilical cord occlusion (UCO). Fetal sheep (118 days’ gestational age (dGA)) were implanted with an inflatable Silastic cuff around the umbilical cord and a microdialysis probe inserted into the right cerebral hemisphere for interstitial fluid sampling. Creatine (6 mg kg(−1) h(−1)) or saline was continuously infused intravenously from 122 dGA. At 131 dGA, a 10 min UCO was induced. Hourly microdialysis samples were obtained from −24 to 72 h post‐UCO and analysed for percentage change of hydroxyl radicals ((•)OH) and interstitial metabolites (lactate, pyruvate, glutamate, glycerol, glycine). Histochemical markers of protein and lipid oxidation were assessed at post‐mortem 72 h post‐UCO. Prior to UCO, creatine treatment reduced pyruvate and glycerol concentrations in the microdialysate outflow. Creatine treatment reduced interstitial cerebral (•)OH outflow 0 to 24 h post‐UCO. Fetuses with higher arterial creatine concentrations before UCO presented with reduced levels of hypoxaemia ([Formula: see text] and [Formula: see text]) during UCO which associated with reduced interstitial cerebral pyruvate, lactate and (•)OH accumulation. No effects of creatine treatment on immunohistochemical markers of oxidative stress were found. In conclusion, fetal creatine treatment decreased cerebral outflow of (•)OH and was associated with an improvement in cerebral bioenergetics following acute hypoxia. [Image: see text] KEY POINTS: Fetal hypoxia can cause persistent metabolic and oxidative stress responses that disturb energy homeostasis in the brain. Creatine in its phosphorylated form is an endogenous phosphagen; therefore, supplementation is a proposed prophylactic treatment for fetal hypoxia. Fetal sheep instrumented with a cerebral microdialysis probe were continuously infused with or without creatine‐monohydrate for 10 days before induction of 10 min umbilical cord occlusion (UCO; 131 days’ gestation). Cerebral interstitial fluid was collected up to 72 h following UCO. Prior to UCO, fetal creatine supplementation reduced interstitial cerebral pyruvate and glycerol concentrations. Fetal creatine supplementation reduced cerebral hydroxyl radical efflux up to 24 h post‐UCO. Fetuses with higher arterial creatine concentrations before UCO and reduced levels of systemic hypoxaemia during UCO were associated with reduced cerebral interstitial pyruvate, lactate and (•)OH following UCO. Creatine supplementation leads to some improvements in cerebral bioenergetics following in utero acute hypoxia. |
format | Online Article Text |
id | pubmed-9542404 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95424042022-10-14 Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep Tran, Nhi Thao Kowalski, Greg M. Muccini, Anna M. Nitsos, Ilias Hale, Nadia Snow, Rod J. Walker, David W. Ellery, Stacey J. J Physiol Placenta, Pregnancy and Perinatal Physiology ABSTRACT: Prophylactic creatine treatment may reduce hypoxic brain injury due to its ability to sustain intracellular ATP levels thereby reducing oxidative and metabolic stress responses during oxygen deprivation. Using microdialysis, we investigated the real‐time in vivo effects of fetal creatine supplementation on cerebral metabolism following acute in utero hypoxia caused by umbilical cord occlusion (UCO). Fetal sheep (118 days’ gestational age (dGA)) were implanted with an inflatable Silastic cuff around the umbilical cord and a microdialysis probe inserted into the right cerebral hemisphere for interstitial fluid sampling. Creatine (6 mg kg(−1) h(−1)) or saline was continuously infused intravenously from 122 dGA. At 131 dGA, a 10 min UCO was induced. Hourly microdialysis samples were obtained from −24 to 72 h post‐UCO and analysed for percentage change of hydroxyl radicals ((•)OH) and interstitial metabolites (lactate, pyruvate, glutamate, glycerol, glycine). Histochemical markers of protein and lipid oxidation were assessed at post‐mortem 72 h post‐UCO. Prior to UCO, creatine treatment reduced pyruvate and glycerol concentrations in the microdialysate outflow. Creatine treatment reduced interstitial cerebral (•)OH outflow 0 to 24 h post‐UCO. Fetuses with higher arterial creatine concentrations before UCO presented with reduced levels of hypoxaemia ([Formula: see text] and [Formula: see text]) during UCO which associated with reduced interstitial cerebral pyruvate, lactate and (•)OH accumulation. No effects of creatine treatment on immunohistochemical markers of oxidative stress were found. In conclusion, fetal creatine treatment decreased cerebral outflow of (•)OH and was associated with an improvement in cerebral bioenergetics following acute hypoxia. [Image: see text] KEY POINTS: Fetal hypoxia can cause persistent metabolic and oxidative stress responses that disturb energy homeostasis in the brain. Creatine in its phosphorylated form is an endogenous phosphagen; therefore, supplementation is a proposed prophylactic treatment for fetal hypoxia. Fetal sheep instrumented with a cerebral microdialysis probe were continuously infused with or without creatine‐monohydrate for 10 days before induction of 10 min umbilical cord occlusion (UCO; 131 days’ gestation). Cerebral interstitial fluid was collected up to 72 h following UCO. Prior to UCO, fetal creatine supplementation reduced interstitial cerebral pyruvate and glycerol concentrations. Fetal creatine supplementation reduced cerebral hydroxyl radical efflux up to 24 h post‐UCO. Fetuses with higher arterial creatine concentrations before UCO and reduced levels of systemic hypoxaemia during UCO were associated with reduced cerebral interstitial pyruvate, lactate and (•)OH following UCO. Creatine supplementation leads to some improvements in cerebral bioenergetics following in utero acute hypoxia. John Wiley and Sons Inc. 2022-06-03 2022-07-01 /pmc/articles/PMC9542404/ /pubmed/35587817 http://dx.doi.org/10.1113/JP282840 Text en © 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Placenta, Pregnancy and Perinatal Physiology Tran, Nhi Thao Kowalski, Greg M. Muccini, Anna M. Nitsos, Ilias Hale, Nadia Snow, Rod J. Walker, David W. Ellery, Stacey J. Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep |
title | Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep |
title_full | Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep |
title_fullStr | Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep |
title_full_unstemmed | Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep |
title_short | Creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep |
title_sort | creatine supplementation reduces the cerebral oxidative and metabolic stress responses to acute in utero hypoxia in the late‐gestation fetal sheep |
topic | Placenta, Pregnancy and Perinatal Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542404/ https://www.ncbi.nlm.nih.gov/pubmed/35587817 http://dx.doi.org/10.1113/JP282840 |
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