Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats

Human and animal studies have demonstrated that neonatal hyperoxia increases oxidative stress and adversely affects glomerular and tubular maturity. This study was undertaken to determine how exposure to neonatal hyperoxia affected kidney morphology and fibrosis and to elucidate the relationship bet...

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Main Authors: Jiunn-Song Jiang, Hsiu-Chu Chou, Tsu-Fu Yeh, Chung-Ming Chen
Format: Article
Language:English
Published: Elsevier 2015-08-01
Series:Pediatrics and Neonatology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1875957214001958
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author Jiunn-Song Jiang
Hsiu-Chu Chou
Tsu-Fu Yeh
Chung-Ming Chen
author_facet Jiunn-Song Jiang
Hsiu-Chu Chou
Tsu-Fu Yeh
Chung-Ming Chen
author_sort Jiunn-Song Jiang
collection DOAJ
description Human and animal studies have demonstrated that neonatal hyperoxia increases oxidative stress and adversely affects glomerular and tubular maturity. This study was undertaken to determine how exposure to neonatal hyperoxia affected kidney morphology and fibrosis and to elucidate the relationship between connective tissue growth factor (CTGF) and collagen expression in rat kidneys. Methods: Sprague–Dawley rat pups were exposed to either hyperoxia or ambient air. The control groups were maintained in ambient air for 1 week and 3 weeks. The hyperoxia groups were exposed to >95% O2 for 1 week and subsequently placed in an environment of 60% O2 for an additional 2 weeks. The animals were euthanized on Postnatal Day 7 or 21 and the kidneys underwent histological analyses and oxidative stress and total collagen measurements. Results: The rats reared in O2-enriched air exhibited significantly higher tubular injury scores (1.4 ± 0.5 vs. 0.7 ± 0.7 on Day 7; 1.4 ± 0.5 vs. 0.6 ± 0.5 on Day 21), a larger proportion of the cortex occupied by glomeruli (25.5 ± 4.1 vs. 21.3 ± 3.1% on Day 7; 20.1 ± 3.5 vs. 17.1 ± 1.7% on Day 21), larger glomerular sizes (84.7 ± 5.8 vs. 77.5 ± 6.1 μm on Day 7; 88.4 ± 2.9 vs. 84.9 ± 3.1 μm on Day 21), and higher total collagen content (54.1 ± 27.5 vs. 18.3 ± 6.3 μg/mg protein on Day 7; 397.4 ± 32.8 vs. 289.5 ± 80.0 μg/mg protein on Day 21) than did rats reared in ambient air. Immunohistochemical expressions of oxidative stress marker 8-hydroxy-2′-deoxyguanosine and CTGF immunoreactivities were significantly higher in the rats reared in O2-enriched air compared with the rats reared in ambient air on Postnatal Days 7 and 21. Conclusion: Neonatal hyperoxia exposure contributes to kidney fibrosis, which is probably caused by activated CTGF expression.
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spelling doaj-art-5947113eb3e44d1bbd051afab2a3c8cf2025-08-20T01:57:04ZengElsevierPediatrics and Neonatology1875-95722015-08-0156423524110.1016/j.pedneo.2014.11.003Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in RatsJiunn-Song Jiang0Hsiu-Chu Chou1Tsu-Fu Yeh2Chung-Ming Chen3Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, TaiwanDepartment of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanMaternal Child Health Research Center, College of Medicine, Taipei Medical University, Taipei, TaiwanMaternal Child Health Research Center, College of Medicine, Taipei Medical University, Taipei, TaiwanHuman and animal studies have demonstrated that neonatal hyperoxia increases oxidative stress and adversely affects glomerular and tubular maturity. This study was undertaken to determine how exposure to neonatal hyperoxia affected kidney morphology and fibrosis and to elucidate the relationship between connective tissue growth factor (CTGF) and collagen expression in rat kidneys. Methods: Sprague–Dawley rat pups were exposed to either hyperoxia or ambient air. The control groups were maintained in ambient air for 1 week and 3 weeks. The hyperoxia groups were exposed to >95% O2 for 1 week and subsequently placed in an environment of 60% O2 for an additional 2 weeks. The animals were euthanized on Postnatal Day 7 or 21 and the kidneys underwent histological analyses and oxidative stress and total collagen measurements. Results: The rats reared in O2-enriched air exhibited significantly higher tubular injury scores (1.4 ± 0.5 vs. 0.7 ± 0.7 on Day 7; 1.4 ± 0.5 vs. 0.6 ± 0.5 on Day 21), a larger proportion of the cortex occupied by glomeruli (25.5 ± 4.1 vs. 21.3 ± 3.1% on Day 7; 20.1 ± 3.5 vs. 17.1 ± 1.7% on Day 21), larger glomerular sizes (84.7 ± 5.8 vs. 77.5 ± 6.1 μm on Day 7; 88.4 ± 2.9 vs. 84.9 ± 3.1 μm on Day 21), and higher total collagen content (54.1 ± 27.5 vs. 18.3 ± 6.3 μg/mg protein on Day 7; 397.4 ± 32.8 vs. 289.5 ± 80.0 μg/mg protein on Day 21) than did rats reared in ambient air. Immunohistochemical expressions of oxidative stress marker 8-hydroxy-2′-deoxyguanosine and CTGF immunoreactivities were significantly higher in the rats reared in O2-enriched air compared with the rats reared in ambient air on Postnatal Days 7 and 21. Conclusion: Neonatal hyperoxia exposure contributes to kidney fibrosis, which is probably caused by activated CTGF expression.http://www.sciencedirect.com/science/article/pii/S1875957214001958collagenconnective tissue growth factor (CTGF)hyperoxia
spellingShingle Jiunn-Song Jiang
Hsiu-Chu Chou
Tsu-Fu Yeh
Chung-Ming Chen
Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats
Pediatrics and Neonatology
collagen
connective tissue growth factor (CTGF)
hyperoxia
title Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats
title_full Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats
title_fullStr Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats
title_full_unstemmed Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats
title_short Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats
title_sort neonatal hyperoxia exposure induces kidney fibrosis in rats
topic collagen
connective tissue growth factor (CTGF)
hyperoxia
url http://www.sciencedirect.com/science/article/pii/S1875957214001958
work_keys_str_mv AT jiunnsongjiang neonatalhyperoxiaexposureinduceskidneyfibrosisinrats
AT hsiuchuchou neonatalhyperoxiaexposureinduceskidneyfibrosisinrats
AT tsufuyeh neonatalhyperoxiaexposureinduceskidneyfibrosisinrats
AT chungmingchen neonatalhyperoxiaexposureinduceskidneyfibrosisinrats