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Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease

The proposed mechanisms for the development of nephropathy are many, complex and often overlapping. Although recent literature strongly supports a role of kidney hypoxia as an independent pathway to nephropathy, the evidence remains inconclusive since the role of hypoxia is difficult to differentiat...

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Autores principales: Sivertsson, Ebba, Friederich-Persson, Malou, Persson, Patrik, Nangaku, Masaomi, Hansell, Peter, Palm, Fredrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893624/
https://www.ncbi.nlm.nih.gov/pubmed/35239685
http://dx.doi.org/10.1371/journal.pone.0264524
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author Sivertsson, Ebba
Friederich-Persson, Malou
Persson, Patrik
Nangaku, Masaomi
Hansell, Peter
Palm, Fredrik
author_facet Sivertsson, Ebba
Friederich-Persson, Malou
Persson, Patrik
Nangaku, Masaomi
Hansell, Peter
Palm, Fredrik
author_sort Sivertsson, Ebba
collection PubMed
description The proposed mechanisms for the development of nephropathy are many, complex and often overlapping. Although recent literature strongly supports a role of kidney hypoxia as an independent pathway to nephropathy, the evidence remains inconclusive since the role of hypoxia is difficult to differentiate from confounding factors such as hyperglycemia, hypertension and oxidative stress. By increasing kidney oxygen consumption using triiodothyronine (T(3)) and, thus, avoiding these confounding factors, the aim of the present study was to investigate renal hypoxia per se as a causal pathway for the development of nephropathy. Healthy Sprague-Dawley rats were treated with T(3) (10 μg/kg/day) and the angiotensin II AT(1)-receptor antagonist candesartan (1 mg/kg in drinking water) to eliminate effects of T(3)-induced renin release; and compared to a candesartan treated control group. After 7 weeks of treatment in vivo kidney function, oxygen metabolism and mitochondrial function were evaluated. T(3) did not affect glomerular filtration rate or renal blood flow, but increased total kidney oxygen consumption resulting in cortical hypoxia. Nephropathy, demonstrated as albuminuria and tubulointerstitial fibrosis, developed in T(3)-treated animals. Mitochondria uncoupling mediated by uncoupling protein 2 and the adenosine nucleotide transporter was demonstrated as a mechanism causing the increased kidney oxygen consumption. Importantly, blood glucose levels, mean arterial blood pressure and oxidative stress levels were not affected by T(3). In conclusion, the present study provides further evidence for increased kidney oxygen consumption causing intrarenal tissue hypoxia, as a causal pathway for development of nephropathy.
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spelling pubmed-88936242022-03-04 Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease Sivertsson, Ebba Friederich-Persson, Malou Persson, Patrik Nangaku, Masaomi Hansell, Peter Palm, Fredrik PLoS One Research Article The proposed mechanisms for the development of nephropathy are many, complex and often overlapping. Although recent literature strongly supports a role of kidney hypoxia as an independent pathway to nephropathy, the evidence remains inconclusive since the role of hypoxia is difficult to differentiate from confounding factors such as hyperglycemia, hypertension and oxidative stress. By increasing kidney oxygen consumption using triiodothyronine (T(3)) and, thus, avoiding these confounding factors, the aim of the present study was to investigate renal hypoxia per se as a causal pathway for the development of nephropathy. Healthy Sprague-Dawley rats were treated with T(3) (10 μg/kg/day) and the angiotensin II AT(1)-receptor antagonist candesartan (1 mg/kg in drinking water) to eliminate effects of T(3)-induced renin release; and compared to a candesartan treated control group. After 7 weeks of treatment in vivo kidney function, oxygen metabolism and mitochondrial function were evaluated. T(3) did not affect glomerular filtration rate or renal blood flow, but increased total kidney oxygen consumption resulting in cortical hypoxia. Nephropathy, demonstrated as albuminuria and tubulointerstitial fibrosis, developed in T(3)-treated animals. Mitochondria uncoupling mediated by uncoupling protein 2 and the adenosine nucleotide transporter was demonstrated as a mechanism causing the increased kidney oxygen consumption. Importantly, blood glucose levels, mean arterial blood pressure and oxidative stress levels were not affected by T(3). In conclusion, the present study provides further evidence for increased kidney oxygen consumption causing intrarenal tissue hypoxia, as a causal pathway for development of nephropathy. Public Library of Science 2022-03-03 /pmc/articles/PMC8893624/ /pubmed/35239685 http://dx.doi.org/10.1371/journal.pone.0264524 Text en © 2022 Sivertsson et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sivertsson, Ebba
Friederich-Persson, Malou
Persson, Patrik
Nangaku, Masaomi
Hansell, Peter
Palm, Fredrik
Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
title Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
title_full Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
title_fullStr Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
title_full_unstemmed Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
title_short Thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
title_sort thyroid hormone increases oxygen metabolism causing intrarenal tissue hypoxia; a pathway to kidney disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8893624/
https://www.ncbi.nlm.nih.gov/pubmed/35239685
http://dx.doi.org/10.1371/journal.pone.0264524
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