The Effects of Fentanyl on Hepatic Mitochondrial Function.

Djafarzadeh, Siamak; Vuda, Madhusudanarao; Jeger, Victor; Takala, Jukka; Jakob, Stephan (2016). The Effects of Fentanyl on Hepatic Mitochondrial Function. Anesthesia and analgesia, 123(2), pp. 311-325. International Anesthesia Research Society 10.1213/ANE.0000000000001280

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BACKGROUND Remifentanil interferes with hepatic mitochondrial function. The aim of the present study was to evaluate whether hepatic mitochondrial function is affected by fentanyl, a more widely used opioid than remifentanil. METHODS Human hepatoma HepG2 cells were exposed to fentanyl or pretreated with naloxone (an opioid receptor antagonist) or 5-hydroxydecanoate (5-HD, an inhibitor of mitochondrial adenosine triphosphate (ATP)-sensitive potassium [mitoKATP] channels), followed by incubation with fentanyl. Mitochondrial function and metabolism were then analyzed. RESULTS Fentanyl marginally reduced maximal mitochondrial complex-specific respiration rates using exogenous substrates (decrease in medians: 11%-18%; P = 0.003-0.001) but did not affect basal cellular respiration rates (P = 0.834). The effect on stimulated respiration was prevented by preincubation with naloxone or 5-HD. Fentanyl reduced cellular ATP content in a dose-dependent manner (P < 0.001), an effect that was not significantly prevented by 5-HD and not explained by increased total ATPase concentration. However, in vitro ATPase activity of recombinant human permeability glycoprotein (an ATP-dependent drug efflux transporter) was significantly stimulated by fentanyl (P = 0.004). CONCLUSIONS Our data suggest that fentanyl reduces stimulated mitochondrial respiration of cultured human hepatocytes by a mechanism that is blocked by a mitoKATP channel antagonist. Increased energy requirements for fentanyl efflux transport may offer an explanation for the substantial decrease in cellular ATP concentration.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care

UniBE Contributor:

Djafarzadeh, Siamak; Takala, Jukka and Jakob, Stephan

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1526-7598

Publisher:

International Anesthesia Research Society

Language:

English

Submitter:

Mirella Aeberhard

Date Deposited:

05 Apr 2017 09:47

Last Modified:

05 Apr 2017 09:47

Publisher DOI:

10.1213/ANE.0000000000001280

PubMed ID:

27089001

BORIS DOI:

10.7892/boris.93478

URI:

https://boris.unibe.ch/id/eprint/93478

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