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Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control
BACKGROUND: Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Brieflands
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024813/ https://www.ncbi.nlm.nih.gov/pubmed/36945337 http://dx.doi.org/10.5812/ijpr-133776 |
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author | Chai, Nannan Zheng, Haihong Zhang, Hao Li, Lingxu Yu, Xue Wang, Liyi Bi, Xin Yang, Lihong Niu, Tongxu Liu, Xiujuan Zhao, Yajun Dong, Lijie |
author_facet | Chai, Nannan Zheng, Haihong Zhang, Hao Li, Lingxu Yu, Xue Wang, Liyi Bi, Xin Yang, Lihong Niu, Tongxu Liu, Xiujuan Zhao, Yajun Dong, Lijie |
author_sort | Chai, Nannan |
collection | PubMed |
description | BACKGROUND: Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-induced heart damage in offspring are required. OBJECTIVES: This study aimed to investigate the preventive effects of prenatal SPD treatment on IUH-induced heart damage in newborn offspring rats and its underlying mitochondrial-related mechanism. METHODS: The rat model of IUH was established by exposure to 10% O(2) seven days before term. Meanwhile, for seven days, the pregnant rats were given SPD (5 mg.kg(-1).d(-1); ip). The one-day offspring rats were sacrificed to assess several parameters, including growth development, heart damage, cardiomyocytes proliferation, myocardial oxidative stress, cell apoptosis, and mitochondrial function, and have mitochondrial quality control (MQC), including mitophagy, mitochondrial biogenesis, and mitochondrial fusion/fission. In in vitro experiments, primary cardiomyocytes were subjected to hypoxia with or without SPD for 24 hours. RESULTS: IUH decreased body weight, heart weight, cardiac Ki67 expression, the activity of SOD, and the CAT and adenosine 5'-triphosphate (ATP) levels and increased the BAX/BCL2 expression, and TUNEL-positive nuclei numbers. Furthermore, IUH also caused mitochondrial structure abnormality, dysfunction, and decreased mitophagy (decreased number of mitophagosomes), declined mitochondrial biogenesis (decreased expression of SIRT-1, PGC-1α, NRF-2, and TFAM), and led to fission/fusion imbalance (increased percentage of mitochondrial fragments, increased DRP1 expression, and decreased MFN2 expression) in the myocardium. Surprisingly, SPD treatment normalized the variations in the IUH-induced parameters. Furthermore, SPD also prevented hypoxia-induced ROS accumulation, mitochondrial membrane potential decay, and the mitophagy decrease in cardiomyocytes. CONCLUSION: Maternal SPD treatment caused IUH-induced heart damage in newborn offspring rats by improving the myocardial mitochondrial function via anti-oxidation and anti-apoptosis, and regulating MQC. |
format | Online Article Text |
id | pubmed-10024813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Brieflands |
record_format | MEDLINE/PubMed |
spelling | pubmed-100248132023-03-20 Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control Chai, Nannan Zheng, Haihong Zhang, Hao Li, Lingxu Yu, Xue Wang, Liyi Bi, Xin Yang, Lihong Niu, Tongxu Liu, Xiujuan Zhao, Yajun Dong, Lijie Iran J Pharm Res Research Article BACKGROUND: Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-induced heart damage in offspring are required. OBJECTIVES: This study aimed to investigate the preventive effects of prenatal SPD treatment on IUH-induced heart damage in newborn offspring rats and its underlying mitochondrial-related mechanism. METHODS: The rat model of IUH was established by exposure to 10% O(2) seven days before term. Meanwhile, for seven days, the pregnant rats were given SPD (5 mg.kg(-1).d(-1); ip). The one-day offspring rats were sacrificed to assess several parameters, including growth development, heart damage, cardiomyocytes proliferation, myocardial oxidative stress, cell apoptosis, and mitochondrial function, and have mitochondrial quality control (MQC), including mitophagy, mitochondrial biogenesis, and mitochondrial fusion/fission. In in vitro experiments, primary cardiomyocytes were subjected to hypoxia with or without SPD for 24 hours. RESULTS: IUH decreased body weight, heart weight, cardiac Ki67 expression, the activity of SOD, and the CAT and adenosine 5'-triphosphate (ATP) levels and increased the BAX/BCL2 expression, and TUNEL-positive nuclei numbers. Furthermore, IUH also caused mitochondrial structure abnormality, dysfunction, and decreased mitophagy (decreased number of mitophagosomes), declined mitochondrial biogenesis (decreased expression of SIRT-1, PGC-1α, NRF-2, and TFAM), and led to fission/fusion imbalance (increased percentage of mitochondrial fragments, increased DRP1 expression, and decreased MFN2 expression) in the myocardium. Surprisingly, SPD treatment normalized the variations in the IUH-induced parameters. Furthermore, SPD also prevented hypoxia-induced ROS accumulation, mitochondrial membrane potential decay, and the mitophagy decrease in cardiomyocytes. CONCLUSION: Maternal SPD treatment caused IUH-induced heart damage in newborn offspring rats by improving the myocardial mitochondrial function via anti-oxidation and anti-apoptosis, and regulating MQC. Brieflands 2023-03-01 /pmc/articles/PMC10024813/ /pubmed/36945337 http://dx.doi.org/10.5812/ijpr-133776 Text en Copyright © 2023, Author(s) https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. |
spellingShingle | Research Article Chai, Nannan Zheng, Haihong Zhang, Hao Li, Lingxu Yu, Xue Wang, Liyi Bi, Xin Yang, Lihong Niu, Tongxu Liu, Xiujuan Zhao, Yajun Dong, Lijie Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control |
title | Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control |
title_full | Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control |
title_fullStr | Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control |
title_full_unstemmed | Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control |
title_short | Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control |
title_sort | spermidine alleviates intrauterine hypoxia-induced offspring newborn myocardial mitochondrial damage in rats by inhibiting oxidative stress and regulating mitochondrial quality control |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024813/ https://www.ncbi.nlm.nih.gov/pubmed/36945337 http://dx.doi.org/10.5812/ijpr-133776 |
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