The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro

Evidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore...

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Main Authors: Erik Nylander, Sofia Zelleroth, Fred Nyberg, Alfhild Grönbladh, Mathias Hallberg
Format: Article
Language:English
Published: MDPI AG 2018-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/19/11/3627
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author Erik Nylander
Sofia Zelleroth
Fred Nyberg
Alfhild Grönbladh
Mathias Hallberg
author_facet Erik Nylander
Sofia Zelleroth
Fred Nyberg
Alfhild Grönbladh
Mathias Hallberg
author_sort Erik Nylander
collection DOAJ
description Evidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore the protective and restorative effects of GH and IGF-1 in methadone-treated cell cultures. Primary cortical cell cultures were harvested from rat fetuses and grown for seven days in vitro. To examine the protective effects, methadone was co-treated with or without GH or IGF-1 for three consecutive days. To examine the restorative effects, methadone was added for the first 24 h, washed, and later treated with GH or IGF-1 for 48 h. At the end of each experiment, mitochondrial function and membrane integrity were evaluated. The results revealed that GH had protective effects in the membrane integrity assay and that both GH and IGF-1 effectively recovered mitochondrial function and membrane integrity in cells pretreated with methadone. The overall conclusion of the present study is that GH, but not IGF-1, protects primary cortical cells against methadone-induced toxicity, and that both GH and IGF-1 have a restorative effect on cells pretreated with methadone.
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spelling doaj.art-9ffb8d42586f4ef4a3b43936ac2e91912022-12-22T03:48:22ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-11-011911362710.3390/ijms19113627ijms19113627The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In VitroErik Nylander0Sofia Zelleroth1Fred Nyberg2Alfhild Grönbladh3Mathias Hallberg4The Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, SwedenThe Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, SwedenThe Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, SwedenThe Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, SwedenThe Beijer Laboratory, Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, Uppsala, SE-751 24, SwedenEvidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore the protective and restorative effects of GH and IGF-1 in methadone-treated cell cultures. Primary cortical cell cultures were harvested from rat fetuses and grown for seven days in vitro. To examine the protective effects, methadone was co-treated with or without GH or IGF-1 for three consecutive days. To examine the restorative effects, methadone was added for the first 24 h, washed, and later treated with GH or IGF-1 for 48 h. At the end of each experiment, mitochondrial function and membrane integrity were evaluated. The results revealed that GH had protective effects in the membrane integrity assay and that both GH and IGF-1 effectively recovered mitochondrial function and membrane integrity in cells pretreated with methadone. The overall conclusion of the present study is that GH, but not IGF-1, protects primary cortical cells against methadone-induced toxicity, and that both GH and IGF-1 have a restorative effect on cells pretreated with methadone.https://www.mdpi.com/1422-0067/19/11/3627growth hormoneinsulin-like growth factor-1neuroprotectionneurorecoverycognitionprimary cell culturesmethadoneopioids
spellingShingle Erik Nylander
Sofia Zelleroth
Fred Nyberg
Alfhild Grönbladh
Mathias Hallberg
The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro
International Journal of Molecular Sciences
growth hormone
insulin-like growth factor-1
neuroprotection
neurorecovery
cognition
primary cell cultures
methadone
opioids
title The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro
title_full The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro
title_fullStr The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro
title_full_unstemmed The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro
title_short The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro
title_sort protective and restorative effects of growth hormone and insulin like growth factor 1 on methadone induced toxicity in vitro
topic growth hormone
insulin-like growth factor-1
neuroprotection
neurorecovery
cognition
primary cell cultures
methadone
opioids
url https://www.mdpi.com/1422-0067/19/11/3627
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