Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats

Abstract Sepsis is a major healthcare concern, especially in the elderly population. The use of an animal model closely resembling clinical conditions in this population may provide a better prediction in translating bench studies to the bedside. Ghrelin inhibits sympathetic nerve activity and infla...

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Main Authors: Weng-Lang Yang, Gaifeng Ma, Mian Zhou, Monowar Aziz, Hao-Ting Yen, Spyros A Marvropoulos, Kaie Ojamaa, Ping Wang
Format: Article
Language:English
Published: BMC 2016-01-01
Series:Molecular Medicine
Online Access:http://link.springer.com/article/10.2119/molmed.2015.00255
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spelling doaj-10524d8ec5e9415b8da02410d00f68e52020-11-25T00:03:26ZengBMCMolecular Medicine1076-15511528-36582016-01-0122112413510.2119/molmed.2015.00255Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic RatsWeng-Lang Yang0Gaifeng Ma1Mian Zhou2Monowar Aziz3Hao-Ting Yen4Spyros A Marvropoulos5Kaie Ojamaa6Ping Wang7TheraSource LLCTheraSource LLCCenter for Immunology and Inflammation, The Feinstein Institute for Medical ResearchCenter for Immunology and Inflammation, The Feinstein Institute for Medical ResearchTheraSource LLCHofstra Northwell School of MedicineCenter for Immunology and Inflammation, The Feinstein Institute for Medical ResearchCenter for Immunology and Inflammation, The Feinstein Institute for Medical ResearchAbstract Sepsis is a major healthcare concern, especially in the elderly population. The use of an animal model closely resembling clinical conditions in this population may provide a better prediction in translating bench studies to the bedside. Ghrelin inhibits sympathetic nerve activity and inflammation in young septic animals; however, aged animals become hyporesponsive to ghrelin. In this study, we evaluated the efficacy of combined human ghrelin and growth hormone (GH) for sepsis treatment in the elderly utilizing a clinically relevant animal model of sepsis. Male Fischer 344 rats 22 to 24 months old were subjected to cecal ligation and puncture (CLP). Human ghrelin plus GH or vehicle (normal saline) was administered subcutaneously at 5 h after CLP. At 20 h after CLP, blood and tissue samples were collected for various analyses. Combined treatment attenuated serum levels of lactate, lactate dehydrogenase, creatinine, blood urea nitrogen, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in aged septic rats. The integrity of the microscopic structure in the lungs, liver and kidneys was well preserved after treatment. Expression of IL-6, TNF-α, macrophage inflammatory protein-2 and keratinocyte-derived chemokine as well as myeloperoxidase activity and caspase-3 activation were significantly reduced in the lungs and liver of treated rats. Moreover, treated rats showed an improvement in cardiovascular function and increased expression of ghrelin receptor and c-fos in the brainstem. Finally, the 10-d survival of aged septic rats was increased from 29% to 64% after combined treatment and was associated with less body weight loss. Our findings warrant the development of combined human ghrelin and GH for sepsis treatment in the geriatric population.http://link.springer.com/article/10.2119/molmed.2015.00255
collection DOAJ
language English
format Article
sources DOAJ
author Weng-Lang Yang
Gaifeng Ma
Mian Zhou
Monowar Aziz
Hao-Ting Yen
Spyros A Marvropoulos
Kaie Ojamaa
Ping Wang
spellingShingle Weng-Lang Yang
Gaifeng Ma
Mian Zhou
Monowar Aziz
Hao-Ting Yen
Spyros A Marvropoulos
Kaie Ojamaa
Ping Wang
Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats
Molecular Medicine
author_facet Weng-Lang Yang
Gaifeng Ma
Mian Zhou
Monowar Aziz
Hao-Ting Yen
Spyros A Marvropoulos
Kaie Ojamaa
Ping Wang
author_sort Weng-Lang Yang
title Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats
title_short Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats
title_full Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats
title_fullStr Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats
title_full_unstemmed Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats
title_sort combined administration of human ghrelin and human growth hormone attenuates organ injury and improves survival in aged septic rats
publisher BMC
series Molecular Medicine
issn 1076-1551
1528-3658
publishDate 2016-01-01
description Abstract Sepsis is a major healthcare concern, especially in the elderly population. The use of an animal model closely resembling clinical conditions in this population may provide a better prediction in translating bench studies to the bedside. Ghrelin inhibits sympathetic nerve activity and inflammation in young septic animals; however, aged animals become hyporesponsive to ghrelin. In this study, we evaluated the efficacy of combined human ghrelin and growth hormone (GH) for sepsis treatment in the elderly utilizing a clinically relevant animal model of sepsis. Male Fischer 344 rats 22 to 24 months old were subjected to cecal ligation and puncture (CLP). Human ghrelin plus GH or vehicle (normal saline) was administered subcutaneously at 5 h after CLP. At 20 h after CLP, blood and tissue samples were collected for various analyses. Combined treatment attenuated serum levels of lactate, lactate dehydrogenase, creatinine, blood urea nitrogen, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in aged septic rats. The integrity of the microscopic structure in the lungs, liver and kidneys was well preserved after treatment. Expression of IL-6, TNF-α, macrophage inflammatory protein-2 and keratinocyte-derived chemokine as well as myeloperoxidase activity and caspase-3 activation were significantly reduced in the lungs and liver of treated rats. Moreover, treated rats showed an improvement in cardiovascular function and increased expression of ghrelin receptor and c-fos in the brainstem. Finally, the 10-d survival of aged septic rats was increased from 29% to 64% after combined treatment and was associated with less body weight loss. Our findings warrant the development of combined human ghrelin and GH for sepsis treatment in the geriatric population.
url http://link.springer.com/article/10.2119/molmed.2015.00255
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