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Mitochondrial function and membrane integrity: an in vitro comparison between six commonly used opioids
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
Vise andre og tillknytning
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Abstract [en]

Introduction: There is an ongoing opioid crisis in the United States where the illicit and non-medical use of prescription opioids is associated with an increasing number of overdose deaths. Few studies have investigated the effects of opioid-induced effects on cell viability, and comparative studies are scarce. Here we examine the toxic effect on cell viability from six commonly used opioids; methadone, morphine, oxycodone, hydromorphone, ketobemidone, and fentanyl with respect to mitochondrial and membrane function in vitro. Methods: The opioids were tested in four different cell cultures; primary cortical cell cultures, human neuroblastoma SH-SY5Y cells, and both differentiated and undifferentiated neuroblastoma/glioma hybrid NG108-15 cells. Results: The six different opioids displayed the same trend of reduced cell viability in all four cell cultures. The ranking of opioids, with respect to reduced cell viability were as follows; methadone, fentanyl, ketobemidone, oxycodone, hydromorphone, and morphine. Conclusion: Methadone was ranked as the most toxic opioid closely followed by fentanyl. Ketobemidone and oxycodone had modest effects while both hydromorphone and morphine only displayed little to no negative impact on cell viability.

Emneord [en]
Methadone, Morphine, Oxycodone, Hydromorphone, Ketobemidone, Fentanyl, Cell viability, primary cell cultures, NG108-15, SH-SY5Y, Opioids
HSV kategori
Forskningsprogram
Farmaceutisk vetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-393205OAI: oai:DiVA.org:uu-393205DiVA, id: diva2:1352091
Tilgjengelig fra: 2019-09-17 Laget: 2019-09-17 Sist oppdatert: 2019-10-04
Inngår i avhandling
1. The effects of growth hormone on opioid-induced toxicity in vitro
Åpne denne publikasjonen i ny fane eller vindu >>The effects of growth hormone on opioid-induced toxicity in vitro
2019 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

There is an ongoing opioid crisis in the United States that is portrayed by a large number of opioid-related deaths. Many of these cases involve commonly used prescription opioids, such as morphine, oxycodone, fentanyl, and methadone. This is concerning and highlights the problems associated with long-term opioid treatment. In addition to opioid-related deaths, long-term opioid use may impact higher brain functions, such as cognitive function. The cause of cognitive decline following opioid treatment may be associated with increased neuronal cell death, inhibited neurogenesis, and altered volumes of specific brain regions important for cognition. Growth hormone (GH), a pituitary hormone regulated by the hypothalamic somatotropic axis, may counteract several of these effects. The hormone, alongside with its mediator insulin-like growth factor-1 (IGF-1), is associated with pro-cognitive effects and display promising neuroprotective actions in the CNS. The main aim for this thesis was to examine the impact of opioids on cell viability and the potentially protective, restorative, and effects linked to pro-cognitive properties of GH in mixed neuronal cell cultures and cell lines. The results clearly display that specific opioids, such as methadone, decrease cell viability, possibly via negative effects on mitochondrial morphology. GH treatment alleviated the negative effects of methadone in cortical cell cultures as well as successfully restored mitochondrial and membrane integrity past injury. Moreover, GH treatment to primary hippocampal cell cultures increased the number of dendritic spines, which are linked to higher cognitive functions, indicating that the hormone act as a cognitive enhancer in the CNS. In conclusion, this thesis provides further evidence that opioids negatively impact cell viability, an effect that may underlie reduced cognitive function as seen in several patients consuming opioids-long term. GH was able to counteract these effects and also able to restore damaged cellular functions. This thesis further confirms the essential role of GH in acting as a cognitive enhancer in the CNS, highlighting the potential role of GH as a treatment for cognitive dysfunctions.    

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2019. s. 60
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 279
Emneord
Growth hormone, opioids, methadone, morphine, ketobemidone, fentanyl, oxycodone, hydromorphone, insulin-like growth factor, cell viability, NG108-15, SH-SY5Y, hippocampus, cortex
HSV kategori
Forskningsprogram
Farmaceutisk vetenskap
Identifikatorer
urn:nbn:se:uu:diva-393940 (URN)978-91-513-0765-7 (ISBN)
Disputas
2019-11-22, B21, Biomedicinskt centrum (BMC), Husargatan 3, Uppsala, 09:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2019-10-30 Laget: 2019-10-04 Sist oppdatert: 2019-11-12

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