Despoina Myrsini Galetaki , Charles L. Cai , Kulsajan S. Bhatia , Vivian Chin , Jacob V. Aranda , Kay D. Beharry
{"title":"间歇性缺氧期间补充鱼油和/或抗氧化剂的新生大鼠生长和碳水化合物代谢的生物标志物","authors":"Despoina Myrsini Galetaki , Charles L. Cai , Kulsajan S. Bhatia , Vivian Chin , Jacob V. Aranda , Kay D. Beharry","doi":"10.1016/j.ghir.2022.101513","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Extremely low gestational age neonates (ELGANs) experience frequent intermittent hypoxia<span><span><span> (IH) episodes during therapeutic oxygen. ELGANs exhibit poor postnatal growth<span> requiring lipid supplementation. Lipids are targets of </span></span>reactive oxygen species<span> resulting in lipid peroxidation and </span></span>cell death<span>, particularly in preterm infants with compromised antioxidant systems. We tested the hypothesis that early supplementation with lipids and/or antioxidants promotes growth and influences biomarkers of carbohydrate metabolism in neonatal rats exposed to IH.</span></span></p></div><div><h3>Design</h3><p><span>Newborn rats (</span><em>n</em><span> = 18/group) were exposed to brief hypoxia (12% O</span><sub>2</sub><span>) during hyperoxia (50% O</span><sub>2</sub><span><span>), or room air (RA), from birth<span> (P0) to P14 during which they received daily oral supplementation with: 1) fish oil; 2) Coenzyme Q10 (CoQ10) in olive oil; 3) </span></span>glutathione<span><span><span><span><span> nanoparticles (nGSH); 4) fish oil+CoQ10; or 5) olive oil. At </span>P21<span>, plasma samples were assessed for glucose, insulin, glucokinase<span> (GCK), glucagon, glucagon-like peptide (GLP)-1, growth hormone (GH), </span></span></span>corticosterone, and </span>ghrelin. Liver was assessed for </span>histopathology<span><span><span>, apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL stain), and GH, insulin-like growth factor (IGF)-I, </span>GH binding protein (GHBP), and </span>IGF binding protein (IGFBP)-3.</span></span></span></p></div><div><h3>Results</h3><p><span><span>Neonatal IH resulted in decreased liver weight and liver/body weight ratios, as well as hepatocyte swelling, steatosis, and apoptosis, which were attenuated with fish oil, nGSH, and combined fish oil+CoQ10. IH also decreased </span>plasma glucose, insulin, GCK, and ghrelin, but increased GLP-1. All </span>treatments improved plasma glucose in IH, but insulin was higher with CoQ10 and nGSH only. Glucagon was increased with CoQ10, fish oil, and CoQ10 + fish oil, while corticosterone was higher with nGSH and CoQ10 + fish oil. IGF-I and IGFBP-3 were significantly higher in the liver with CoQ10 in IH, while deficits in GH were noted with CoQ10 and fish oil in RA and IH. Treatment with nGSH and combined CoQ10 + fish oil reduced IGF-I in RA and IH but increased IGFBP-3.</p></div><div><h3>Conclusions</h3><p>Neonatal IH impairs liver growth with significant hepatocyte damage. Of all supplements in IH, nGSH and combined fish oil+CoQ10 were most effective for preserving liver growth and carbohydrate metabolism. Data suggest that these supplements may improve poor postnatal organ and body growth; and metabolic dysfunction associated with neonatal IH.</p></div>","PeriodicalId":12803,"journal":{"name":"Growth Hormone & Igf Research","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Biomarkers of growth and carbohydrate metabolism in neonatal rats supplemented with fish oil and/or antioxidants during intermittent hypoxia\",\"authors\":\"Despoina Myrsini Galetaki , Charles L. Cai , Kulsajan S. Bhatia , Vivian Chin , Jacob V. Aranda , Kay D. Beharry\",\"doi\":\"10.1016/j.ghir.2022.101513\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>Extremely low gestational age neonates (ELGANs) experience frequent intermittent hypoxia<span><span><span> (IH) episodes during therapeutic oxygen. ELGANs exhibit poor postnatal growth<span> requiring lipid supplementation. Lipids are targets of </span></span>reactive oxygen species<span> resulting in lipid peroxidation and </span></span>cell death<span>, particularly in preterm infants with compromised antioxidant systems. We tested the hypothesis that early supplementation with lipids and/or antioxidants promotes growth and influences biomarkers of carbohydrate metabolism in neonatal rats exposed to IH.</span></span></p></div><div><h3>Design</h3><p><span>Newborn rats (</span><em>n</em><span> = 18/group) were exposed to brief hypoxia (12% O</span><sub>2</sub><span>) during hyperoxia (50% O</span><sub>2</sub><span><span>), or room air (RA), from birth<span> (P0) to P14 during which they received daily oral supplementation with: 1) fish oil; 2) Coenzyme Q10 (CoQ10) in olive oil; 3) </span></span>glutathione<span><span><span><span><span> nanoparticles (nGSH); 4) fish oil+CoQ10; or 5) olive oil. At </span>P21<span>, plasma samples were assessed for glucose, insulin, glucokinase<span> (GCK), glucagon, glucagon-like peptide (GLP)-1, growth hormone (GH), </span></span></span>corticosterone, and </span>ghrelin. Liver was assessed for </span>histopathology<span><span><span>, apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL stain), and GH, insulin-like growth factor (IGF)-I, </span>GH binding protein (GHBP), and </span>IGF binding protein (IGFBP)-3.</span></span></span></p></div><div><h3>Results</h3><p><span><span>Neonatal IH resulted in decreased liver weight and liver/body weight ratios, as well as hepatocyte swelling, steatosis, and apoptosis, which were attenuated with fish oil, nGSH, and combined fish oil+CoQ10. IH also decreased </span>plasma glucose, insulin, GCK, and ghrelin, but increased GLP-1. All </span>treatments improved plasma glucose in IH, but insulin was higher with CoQ10 and nGSH only. Glucagon was increased with CoQ10, fish oil, and CoQ10 + fish oil, while corticosterone was higher with nGSH and CoQ10 + fish oil. IGF-I and IGFBP-3 were significantly higher in the liver with CoQ10 in IH, while deficits in GH were noted with CoQ10 and fish oil in RA and IH. Treatment with nGSH and combined CoQ10 + fish oil reduced IGF-I in RA and IH but increased IGFBP-3.</p></div><div><h3>Conclusions</h3><p>Neonatal IH impairs liver growth with significant hepatocyte damage. Of all supplements in IH, nGSH and combined fish oil+CoQ10 were most effective for preserving liver growth and carbohydrate metabolism. Data suggest that these supplements may improve poor postnatal organ and body growth; and metabolic dysfunction associated with neonatal IH.</p></div>\",\"PeriodicalId\":12803,\"journal\":{\"name\":\"Growth Hormone & Igf Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Growth Hormone & Igf Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1096637422000703\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Growth Hormone & Igf Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1096637422000703","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Biomarkers of growth and carbohydrate metabolism in neonatal rats supplemented with fish oil and/or antioxidants during intermittent hypoxia
Objective
Extremely low gestational age neonates (ELGANs) experience frequent intermittent hypoxia (IH) episodes during therapeutic oxygen. ELGANs exhibit poor postnatal growth requiring lipid supplementation. Lipids are targets of reactive oxygen species resulting in lipid peroxidation and cell death, particularly in preterm infants with compromised antioxidant systems. We tested the hypothesis that early supplementation with lipids and/or antioxidants promotes growth and influences biomarkers of carbohydrate metabolism in neonatal rats exposed to IH.
Design
Newborn rats (n = 18/group) were exposed to brief hypoxia (12% O2) during hyperoxia (50% O2), or room air (RA), from birth (P0) to P14 during which they received daily oral supplementation with: 1) fish oil; 2) Coenzyme Q10 (CoQ10) in olive oil; 3) glutathione nanoparticles (nGSH); 4) fish oil+CoQ10; or 5) olive oil. At P21, plasma samples were assessed for glucose, insulin, glucokinase (GCK), glucagon, glucagon-like peptide (GLP)-1, growth hormone (GH), corticosterone, and ghrelin. Liver was assessed for histopathology, apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling, TUNEL stain), and GH, insulin-like growth factor (IGF)-I, GH binding protein (GHBP), and IGF binding protein (IGFBP)-3.
Results
Neonatal IH resulted in decreased liver weight and liver/body weight ratios, as well as hepatocyte swelling, steatosis, and apoptosis, which were attenuated with fish oil, nGSH, and combined fish oil+CoQ10. IH also decreased plasma glucose, insulin, GCK, and ghrelin, but increased GLP-1. All treatments improved plasma glucose in IH, but insulin was higher with CoQ10 and nGSH only. Glucagon was increased with CoQ10, fish oil, and CoQ10 + fish oil, while corticosterone was higher with nGSH and CoQ10 + fish oil. IGF-I and IGFBP-3 were significantly higher in the liver with CoQ10 in IH, while deficits in GH were noted with CoQ10 and fish oil in RA and IH. Treatment with nGSH and combined CoQ10 + fish oil reduced IGF-I in RA and IH but increased IGFBP-3.
Conclusions
Neonatal IH impairs liver growth with significant hepatocyte damage. Of all supplements in IH, nGSH and combined fish oil+CoQ10 were most effective for preserving liver growth and carbohydrate metabolism. Data suggest that these supplements may improve poor postnatal organ and body growth; and metabolic dysfunction associated with neonatal IH.
期刊介绍:
Growth Hormone & IGF Research is a forum for research on the regulation of growth and metabolism in humans, animals, tissues and cells. It publishes articles on all aspects of growth-promoting and growth-inhibiting hormones and factors, with particular emphasis on insulin-like growth factors (IGFs) and growth hormone. This reflects the increasing importance of growth hormone and IGFs in clinical medicine and in the treatment of diseases.