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This article is part of the supplement: 33rd International Symposium on Intensive Care and Emergency Medicine

Poster presentation

Involvement of mitochondrial ATP-sensitive K+ channels in fentanyl-induced mitochondrial dysfunction of cultured human hepatocytes

S Djafarzadeh*, M Vuda, J Takala and SM Jakob

  • * Corresponding author: S Djafarzadeh

Author Affiliations

Bern University Hospital (Inselspital) and University of Bern, Switzerland

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Critical Care 2013, 17(Suppl 2):P387  doi:10.1186/cc12325


The electronic version of this article is the complete one and can be found online at: http://ccforum.com/content/17/S2/P387


Published:19 March 2013

© 2013 Djafarzadeh et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction

Pharmacological agents used to treat critically ill patients may alter mitochondrial function. The aim of the present study was to investigate whether fentanyl, a commonly used analgesic drug, interacts with hepatic mitochondrial function.

Methods

The human hepatoma cell line HepG2 was exposed to fentanyl at 0.5, 2 or 10 ng/ml for 1 hour, or pretreated with naloxone (an opioid receptor antagonist) at 200 ng/ml or 5-hydroxydecanoate (5-HD; a specific inhibitor of mitochondrial ATP-sensitive K+ (KATP) channels) at 50 μM for 30 minutes, followed by incubation with fentanyl at 2 ng/ml for an additional hour. The mitochondrial complex I-dependent, II-dependent and IV-dependent oxygen consumption rates of the permeabilized cells were measured using a high-resolution oxygraph (Oxygraph-2k; Oroboros Instruments, Innsbruck, Austria). The respiratory electron transfer capacity of intact cells was evaluated using FCCP (carbonyl cyanide p-trifluoromethoxyphenylhydrazone) to obtain the maximum flux.

Results

Incubation of HepG2 cells with fentanyl (1 hour, 2 ng/ml) induced a reduction in complex II-dependent and IV-dependent respiration (Figure 1). Cells pretreated with 5-HD before the addition of fentanyl exhibited no significant changes in complex activities in comparison with controls. Pretreatment with naloxone tended to abolish the fentanyl-induced mitochondrial dysfunction. Treatment with fentanyl led to a reduction in cellular ATP content (0.24 ± 0.06 in controls vs. 0.17 ± 0.14 μmol/mg cellular protein in stimulated cells; P = 0.02). We did not observe any difference in basal or FCCP-uncoupled respiration rates of cells treated with fentanyl at 2 ng/ml compared with controls (data not shown).

Conclusion

Fentanyl reduces cultured human hepatocyte mitochondrial respiration by a mechanism that is blocked by a KATP channel antagonist. In contrast, antagonism with naloxone does not seem to completely abolish the effect of fentanyl.

thumbnailFigure 1. Cellular oxygen consumption after incubation with fentanyl, naloxone or 5-HD.

Acknowledgement

This study was supported by the Swiss National Science Foundation (grant number 32003B_127619).