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Kinetic characteristics of propofol-induced inhibition of electron-transfer chain and fatty acid oxidation in human and rodent skeletal and cardiac muscles


Autoři: Tomáš Urban aff001;  Petr Waldauf aff001;  Adéla Krajčová aff001;  Kateřina Jiroutková aff001;  Milada Halačová aff001;  Valér Džupa aff002;  Libor Janoušek aff003;  Eva Pokorná aff004;  František Duška aff001
Působiště autorů: OXYLAB – Mitochondrial Physiology Lab: Charles University, 3 Faculty of Medicine and FNKV University Hospital, Prague, Czech Republic aff001;  Department of Orthopaedics and Traumatology, Charles University, 3 Faculty of Medicine and FNKV University Hospital, Prague, Czech Republic aff002;  Transplantation Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic aff003;  Department of Organ Recovery and Transplantation Databases, Institute for Clinical and Experimental Medicine, Prague, Czech Republic aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0217254

Souhrn

Introduction

Propofol causes a profound inhibition of fatty acid oxidation and reduces spare electron transfer chain capacity in a range of human and rodent cells and tissues–a feature that might be related to the pathogenesis of Propofol Infusion Syndrome. We aimed to explore the mechanism of propofol-induced alteration of bioenergetic pathways by describing its kinetic characteristics.

Methods

We obtained samples of skeletal and cardiac muscle from Wistar rat (n = 3) and human subjects: vastus lateralis from hip surgery patients (n = 11) and myocardium from brain-dead organ donors (n = 10). We assessed mitochondrial functional indices using standard SUIT protocol and high resolution respirometry in fresh tissue homogenates with or without short-term exposure to a range of propofol concentration (2.5–100 μg/ml). After finding concentrations of propofol causing partial inhibition of a particular pathways, we used that concentration to construct kinetic curves by plotting oxygen flux against substrate concentration during its stepwise titration in the presence or absence of propofol. By spectrophotometry we also measured the influence of the same propofol concentrations on the activity of isolated respiratory complexes.

Results

We found that human muscle and cardiac tissues are more sensitive to propofol-mediated inhibition of bioenergetic pathways than rat’s tissue. In human homogenates, palmitoyl carnitine-driven respiration was inhibited at much lower concentrations of propofol than that required for a reduction of electron transfer chain capacity, suggesting FAO inhibition mechanism different from downstream limitation or carnitine-palmitoyl transferase-1 inhibition. Inhibition of Complex I was characterised by more marked reduction of Vmax, in keeping with non-competitive nature of the inhibition and the pattern was similar to the inhibition of Complex II or electron transfer chain capacity. There was neither inhibition of Complex IV nor increased leak through inner mitochondrial membrane with up to 100 μg/ml of propofol. If measured in isolation by spectrophotometry, propofol 10 μg/ml did not affect the activity of any respiratory complexes.

Conclusion

In human skeletal and heart muscle homogenates, propofol in concentrations that are achieved in propofol-anaesthetized patients, causes a direct inhibition of fatty acid oxidation, in addition to inhibiting flux of electrons through inner mitochondrial membrane. The inhibition is more marked in human as compared to rodent tissues.

Klíčová slova:

Bioenergetics – Cardiac muscles – Fatty acids – Mitochondria – Oxidation – Oxygen – Rodents – Skeletal muscles


Zdroje

1. Madera Sharline, Shipman William and R N. Application to Add Propofol to the Model List of Essential Medicines. J Chem Inf Model. 2013;53: 1689–1699.

2. Wong JM. Propofol infusion syndrome. Am J Ther. 2010;17(5): 487–91. doi: 10.1097/MJT.0b013e3181ed837a 20844346

3. Vasile B, Rasulo F, Candiani A, Latronico N. The pathophysiology of propofol infusion syndrome: A simple name for a complex syndrome. Intensive Care Med. 2003;29(9): 1417–25. doi: 10.1007/s00134-003-1905-x 12904852

4. Krajčová A, Waldauf P, Anděl M, Duška F. Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports. Crit Care. 2015;19: 398. doi: 10.1186/s13054-015-1112-5 26558513

5. Branca D, Roberti MS, Lorenzin P, Vincenti E S G. Influence of the anesthetic 2,6-diisopropylphenol on the oxidative phosphorylation of isolated rat liver mitochondria. Biochem Pharmacol. 1991;42(1): 87–90. doi: 10.1016/0006-2952(91)90684-w 2069600

6. Branca D, Vincenti E S G. Influence of the anesthetic 2,6-diisopropylphenol (propofol) on isolated rat heart mitochondria. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1995;110(1): 41–5. doi: 10.1016/0742-8413(94)00078-O 7749602

7. Branca D, Roberti MS, Vincenti E S G. Uncoupling effect of the general anesthetic 2,6-diisopropylphenol in isolated rat liver mitochondria. Arch Biochem Biophys. 1991;290(2): 517–21. doi: 10.1016/0003-9861(91)90575-4 1656882

8. Rigoulet M, Devin A, Avéret N, Vandais B, Guérin B. Mechanisms of inhibition and uncoupling of respiration in isolated rat liver mitochondria by the general anesthetic 2,6-diisopropylphenol. Eur J Biochem. 1996;241(1): 280–5. doi: 10.1111/j.1432-1033.1996.0280t.x 8898917

9. Tong XX, Kang Y, Liu FZ, Zhang WS L J. [Effect of prolonged infusion of propofol on the liver mitochondria respiratory function in rabbits]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2010;41(6): 1021–3. 21265107

10. Krajčová A, Løvsletten NG, Waldauf P, Frič V, Elkalaf M, Urban T, et al. Effects of Propofol on Cellular Bioenergetics in Human Skeletal Muscle Cells. Crit Care Med. 2017;46(3): e206–e212. doi: 10.1097/CCM.0000000000002875 29240609

11. Wolf A, Weir P, Segar P, Stone J. Impaired fatty acid oxidation in propofol infusion syndrome Relation between occurrence of type 1 diabetes and asthma. Lancet. 2001;357(9256): 606–7.

12. Wolf AR, Potter F. Propofol infusion in children: When does an anesthetic tool become an intensive care liability? Paediatr Anaesth. 2004;14(6): 435–8. doi: 10.1111/j.1460-9592.2004.01332.x 15153202

13. Withington DE, Decell MK, Al Ayed T. A case of propofol toxicity: Further evidence for a causal mechanism. Paediatr Anaesth. 2004;14(6): 505–8. doi: 10.1111/j.1460-9592.2004.01299.x 15153216

14. Vanlander AV, Okun JG, De Jaeger A, Smet J, De Latter E, De Paepe B, et al. Possible pathogenic mechanism of propofol infusion syndrome involves coenzyme Q. Anesthesiology. 2015;122(2): 343–52. doi: 10.1097/ALN.0000000000000484 25296107

15. Sumi C, Okamoto A, Tanaka H, Nishi K, Kusunoki M, Shoji T, et al. Propofol induces a metabolic switch to glycolysis and cell death in a mitochondrial electron transport chain-dependent manner. PLoS One. 2018;13(2): e0192796. doi: 10.1371/journal.pone.0192796 29447230

16. Sumi C, Okamoto A, Tanaka H, Kusunoki M, Shoji T, Uba T, et al. Suppression of mitochondrial oxygen metabolism mediated by the transcription factor HIF-1 alleviates propofol-induced cell toxicity. Sci Rep. 2018;8(1): 8987. doi: 10.1038/s41598-018-27220-8 29895831

17. Ziak J, Krajcova A, Jiroutkova K, Nemcova V, Dzupa V, Duska F. Assessing the function of mitochondria in cytosolic context in human skeletal muscle: Adopting high-resolution respirometry to homogenate of needle biopsy tissue samples. Mitochondrion. 2015;21: 106–12. doi: 10.1016/j.mito.2015.02.002 25701243

18. Fontana-Ayoub, M Fasching M, Gnaiger E. http://wiki.oroboros.at/images/3/3c/MiPNet03.02_Chemicals-Media.pdf. In: Mitochondrial physiology network. 2016 pp. 1–10.

19. Krajčová A, Megvinet D, Urban T, Waldauf P, Hlavička J, Budera P, et al. High resolution respirometry to assess function of mitochondria in native homogenates of human heart muscle. Circ Res (under Rev. 2018;).

20. Dykens JA, Will Y. Drug-Induced Mitochondrial Dysfunction. John Wiley & Sons, Inc.; 2008. doi: 10.1002/9780470372531

21. Lanza I, Nair K. Functional assessment of isolated mitochondria in vitro. Methods Enzym. 2009;457: 349–72. doi: 10.1016/S0076-6879(09)05020-4 19426878

22. Gnaiger E. https://www.researchgate.net/profile/Erich_Gnaiger/publication/267851204_Oxygen_Solubility_in_Experimental_Media/links/553dd3eb0cf29b5ee4bce1d6/Oxygen-Solubility-in-Experimental-Media.pdf. In: Mitochondrial physiology network. 2010 pp. 1–12.

23. Herregods L, Rolly G, Versichelen L, Rosseel MT. Propofol combined with nitrous oxide-oxygen for induction and maintenance of anaesthesia. Anaesthesia. 1987;42(4): 360–5. doi: 10.1111/j.1365-2044.1987.tb03975.x 3496022

24. Casati A, Fanelli G, Casaletti E, Colnaghi E, Cedrati V, Torri G. Clinical assessment of target-controlled infusion of propofol during monitored anesthesia care. Can J Anaesth. 1999;46(3): 235–9. doi: 10.1007/BF03012602 10210047

25. Rigoulet M, Devin A, Avéret N, Vandais B, Guérin B. Mechanisms of inhibition and uncoupling of respiration in isolated rat liver mitochondria by the general anesthetic 2,6-diisopropylphenol. Eur J Biochem. 1996;241: 280–5. doi: 10.1111/j.1432-1033.1996.0280t.x 8898917

26. Spinazzi M, Casarin A, Pertegato V, Salviati L, Angelini C. Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells. Nat Protoc. 2012;7(6): 1235–46. doi: 10.1038/nprot.2012.058 22653162

27. Diedrich DA, Brown DR. Analytic Reviews: Propofol Infusion Syndrome in the ICU. J Intensive Care Med. 2011;26(2): 59–72. doi: 10.1177/0885066610384195 21464061

28. Vollmer JP, Haen S, Wolburg H, Lehmann R, Steiner J, Reddersen S, et al. Propofol Related Infusion Syndrome: Ultrastructural Evidence for a Mitochondrial Disorder. Crit Care Med. 2018;46(1): e91–e94. doi: 10.1097/CCM.0000000000002802 29252954

29. Schenkman KA, Yan S. Propofol impairment of mitochondrial respiration isolated perfused guinea pig hearts determined by reflectance spectroscopy. Crit Care Med. 2000;28(1): 172–7. doi: 10.1097/00003246-200001000-00028 10667518

30. Campos S, Félix L, Venâncio C, Antunes L, Peixoto F. Decrease of state III mitochondrial respiration by prolonged infusion of propofol vehicle in rabbit liver. Eur J Anaesthesiol. 2013;30: 154–154. doi: 10.1097/00003643-201306001-00479


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