Abstract
We separately studied the antioxidant properties of propofol (PPF), Diprivan (the commercial form of PPF) and intralipid (IL) (the vehicle solution of PPF in Diprivan) on active oxygen species produced by phorbol myristate acetate (10(-6) M)-stimulated human polymorphonuclear leukocytes (PMN: 5 x 10(5) cells/assay), human endothelial cells (5 x 10(5) cells/assay) or cell-free systems (NaOCl or H2O2/peroxidase systems), using luminol (10(-4) M)-enhanced chemiluminescence (CL). We also studied the protective effects of Diprivan on endothelial cells submitted to an oxidant stress induced by H2O2/MPO system: cytotoxicity was assessed by the release of preincorporated 51Cr. Propofol inhibited the CL produced by stimulated PMN in a dose dependent manner (until 5 x 10(-5) M, a clinically relevant concentration), while Diprivan and IL were not dose-dependent inhibitors. The CL produced by endothelial cells was dose-dependently inhibited by Diprivan and PPF, and weakly by IL (not dose-dependent). In cell free systems, dose-dependent inhibitions were obtained for the three products with a lower effect for IL. Diprivan efficaciously protected endothelial cells submitted to an oxidant stress, while IL was ineffective. By HPLC, we demonstrated that PPF was not incorporated into the cells. The drug thus acted by scavenging the active oxygen species released in the extracellular medium. IL acted in the same manner, but was a less powerful antioxidant.
Full Text
The Full Text of this article is available as a PDF (219.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aarts L., van der Hee R., Dekker I., de Jong J., Langemeijer H., Bast A. The widely used anesthetic agent propofol can replace alpha-tocopherol as an antioxidant. FEBS Lett. 1995 Jan 2;357(1):83–85. doi: 10.1016/0014-5793(94)01337-z. [DOI] [PubMed] [Google Scholar]
- Archer S. L., Nelson D. P., Weir E. K. Detection of activated O2 species in vitro and in rat lungs by chemiluminescence. J Appl Physiol (1985) 1989 Nov;67(5):1912–1921. doi: 10.1152/jappl.1989.67.5.1912. [DOI] [PubMed] [Google Scholar]
- Davidson J. A., Boom S. J., Pearsall F. J., Zhang P., Ramsay G. Comparison of the effects of four i.v. anaesthetic agents on polymorphonuclear leucocyte function. Br J Anaesth. 1995 Mar;74(3):315–318. doi: 10.1093/bja/74.3.315. [DOI] [PubMed] [Google Scholar]
- English D., Roloff J. S., Lukens J. N., Parker P., Greene H. L., Ghishan F. K. Intravenous lipid emulsions and human neutrophil function. J Pediatr. 1981 Dec;99(6):913–916. doi: 10.1016/s0022-3476(81)80019-4. [DOI] [PubMed] [Google Scholar]
- Eriksson O. Effects of the general anaesthetic Propofol on the Ca2(+)-induced permeabilization of rat liver mitochondria. FEBS Lett. 1991 Feb 11;279(1):45–48. doi: 10.1016/0014-5793(91)80246-y. [DOI] [PubMed] [Google Scholar]
- Eriksson O., Pollesello P., Saris N. E. Inhibition of lipid peroxidation in isolated rat liver mitochondria by the general anaesthetic propofol. Biochem Pharmacol. 1992 Jul 22;44(2):391–393. doi: 10.1016/0006-2952(92)90026-f. [DOI] [PubMed] [Google Scholar]
- Fröhlich D., Rothe G., Schwall B., Schmitz G., Hobbhahn J., Taeger K. Thiopentone and propofol, but not methohexitone nor midazolam, inhibit neutrophil oxidative responses to the bacterial peptide FMLP. Eur J Anaesthesiol. 1996 Nov;13(6):582–588. doi: 10.1046/j.1365-2346.1996.d01-405.x. [DOI] [PubMed] [Google Scholar]
- Fujishima S., Aikawa N. Neutrophil-mediated tissue injury and its modulation. Intensive Care Med. 1995 Mar;21(3):277–285. doi: 10.1007/BF01701489. [DOI] [PubMed] [Google Scholar]
- Hans P., Deby-Dupont G., Deby C., Pieron F., Verbesselt R., Franssen C., Lamy M. Increase in antioxidant capacity of plasma during propofol anesthesia. J Neurosurg Anesthesiol. 1997 Jul;9(3):234–236. doi: 10.1097/00008506-199707000-00006. [DOI] [PubMed] [Google Scholar]
- Hans P., Deby C., Deby-Dupont G., Vrijens B., Albert A., Lamy M. Effect of propofol on in vitro lipid peroxidation induced by different free radical generating systems: a comparison with vitamin E. J Neurosurg Anesthesiol. 1996 Apr;8(2):154–158. doi: 10.1097/00008506-199604000-00010. [DOI] [PubMed] [Google Scholar]
- Heine J., Leuwer M., Scheinichen D., Arseniev L., Jaeger K., Piepenbrock S. Flow cytometry evaluation of the in vitro influence of four i.v. anaesthetics on respiratory burst of neutrophils. Br J Anaesth. 1996 Sep;77(3):387–392. doi: 10.1093/bja/77.3.387. [DOI] [PubMed] [Google Scholar]
- Hulse D., Kusel J. R., O'Donnell N. G., Wilkinson P. C. Effects of anaesthetics on membrane mobility and locomotor responses of human neutrophils. FEMS Immunol Med Microbiol. 1994 Mar;8(3):241–248. doi: 10.1111/j.1574-695X.1994.tb00449.x. [DOI] [PubMed] [Google Scholar]
- Ingold K. U., Webb A. C., Witter D., Burton G. W., Metcalfe T. A., Muller D. P. Vitamin E remains the major lipid-soluble, chain-breaking antioxidant in human plasma even in individuals suffering severe vitamin E deficiency. Arch Biochem Biophys. 1987 Nov 15;259(1):224–225. doi: 10.1016/0003-9861(87)90489-9. [DOI] [PubMed] [Google Scholar]
- Jensen A. G., Dahlgren C., Eintrei C. Propofol decreases random and chemotactic stimulated locomotion of human neutrophils in vitro. Br J Anaesth. 1993 Jan;70(1):99–100. doi: 10.1093/bja/70.1.99. [DOI] [PubMed] [Google Scholar]
- Kahraman S., Demiryürek A. T. Propofol is a peroxynitrite scavenger. Anesth Analg. 1997 May;84(5):1127–1129. doi: 10.1097/00000539-199705000-00032. [DOI] [PubMed] [Google Scholar]
- Kelicen P., Ismailoglu U. B., Erdemli O., Sahin-Erdemli I. The effect of propofol and thiopentone on impairment by reactive oxygen species of endothelium-dependent relaxation in rat aortic rings. Eur J Anaesthesiol. 1997 May;14(3):310–315. doi: 10.1046/j.1365-2346.1997.00110.x. [DOI] [PubMed] [Google Scholar]
- Kochs E., Hoffman W. E., Werner C., Thomas C., Albrecht R. F., Schulte am Esch J. The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. Anesthesiology. 1992 Feb;76(2):245–252. doi: 10.1097/00000542-199202000-00014. [DOI] [PubMed] [Google Scholar]
- Krumholz W., Endrass J., Hempelmann G. Propofol inhibits phagocytosis and killing of Staphylococcus aureus and Escherichia coli by polymorphonuclear leukocytes in vitro. Can J Anaesth. 1994 May;41(5 Pt 1):446–449. doi: 10.1007/BF03009871. [DOI] [PubMed] [Google Scholar]
- Kvam C., Granese D., Flaibani A., Pollesello P., Paoletti S. Hyaluronan can be protected from free-radical depolymerisation by 2,6-diisopropylphenol, a novel radical scavenger. Biochem Biophys Res Commun. 1993 Jun 30;193(3):927–933. doi: 10.1006/bbrc.1993.1714. [DOI] [PubMed] [Google Scholar]
- Mouithys-Mickalad A., Hans P., Deby-Dupont G., Hoebeke M., Deby C., Lamy M. Propofol reacts with peroxynitrite to form a phenoxyl radical: demonstration by electron spin resonance. Biochem Biophys Res Commun. 1998 Aug 28;249(3):833–837. doi: 10.1006/bbrc.1998.9235. [DOI] [PubMed] [Google Scholar]
- Murphy P. G., Bennett J. R., Myers D. S., Davies M. J., Jones J. G. The effect of propofol anaesthesia on free radical-induced lipid peroxidation in rat liver microsomes. Eur J Anaesthesiol. 1993 Jul;10(4):261–266. [PubMed] [Google Scholar]
- Murphy P. G., Davies M. J., Columb M. O., Stratford N. Effect of propofol and thiopentone on free radical mediated oxidative stress of the erythrocyte. Br J Anaesth. 1996 Apr;76(4):536–543. doi: 10.1093/bja/76.4.536. [DOI] [PubMed] [Google Scholar]
- Murphy P. G., Ogilvy A. J., Whiteley S. M. The effect of propofol on the neutrophil respiratory burst. Eur J Anaesthesiol. 1996 Sep;13(5):471–473. doi: 10.1046/j.1365-2346.1996.00003.x. [DOI] [PubMed] [Google Scholar]
- Musacchio E., Rizzoli V., Bianchi M., Bindoli A., Galzigna L. Antioxidant action of propofol on liver microsomes, mitochondria and brain synaptosomes in the rat. Pharmacol Toxicol. 1991 Jul;69(1):75–77. doi: 10.1111/j.1600-0773.1991.tb00414.x. [DOI] [PubMed] [Google Scholar]
- O'Donnell N. G., McSharry C. P., Wilkinson P. C., Asbury A. J. Comparison of the inhibitory effect of propofol, thiopentone and midazolam on neutrophil polarization in vitro in the presence or absence of human serum albumin. Br J Anaesth. 1992 Jul;69(1):70–74. doi: 10.1093/bja/69.1.70. [DOI] [PubMed] [Google Scholar]
- Plummer G. F. Improved method for the determination of propofol in blood by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1987 Oct 9;421(1):171–176. doi: 10.1016/0378-4347(87)80394-8. [DOI] [PubMed] [Google Scholar]
- Rosen G. M., Pou S., Ramos C. L., Cohen M. S., Britigan B. E. Free radicals and phagocytic cells. FASEB J. 1995 Feb;9(2):200–209. doi: 10.1096/fasebj.9.2.7540156. [DOI] [PubMed] [Google Scholar]
- Skoutelis A., Lianou P., Papageorgiou E., Kokkinis K., Alexopoulos K., Bassaris H. Effects of propofol and thiopentone on polymorphonuclear leukocyte functions in vitro. Acta Anaesthesiol Scand. 1994 Nov;38(8):858–862. doi: 10.1111/j.1399-6576.1994.tb04018.x. [DOI] [PubMed] [Google Scholar]
- Tian Y. K., Weiss M., Schneider M. Effects of sedatives and their solvents on the neutrophil granulocyte function. J Tongji Med Univ. 1994;14(2):85–88. [PubMed] [Google Scholar]
- Weiss M., Birkhahn A., Krone M., Schneider E. M. Do etomidate and propofol influence oxygen radical production of neutrophils? Immunopharmacol Immunotoxicol. 1996 May;18(2):291–307. doi: 10.3109/08923979609052737. [DOI] [PubMed] [Google Scholar]
- Weiss M., Buhl R., Medve M., Schneider E. M. Tumor necrosis factor-alpha modulates the selective interference of hypnotics and sedatives to suppress N-formyl-methionyl-leucyl-phenylalanine-induced oxidative burst formation in neutrophils. Crit Care Med. 1997 Jan;25(1):128–134. doi: 10.1097/00003246-199701000-00024. [DOI] [PubMed] [Google Scholar]
- Weiss S. J. Tissue destruction by neutrophils. N Engl J Med. 1989 Feb 9;320(6):365–376. doi: 10.1056/NEJM198902093200606. [DOI] [PubMed] [Google Scholar]
- Young Y., Menon D. K., Tisavipat N., Matta B. F., Jones J. G. Propofol neuroprotection in a rat model of ischaemia reperfusion injury. Eur J Anaesthesiol. 1997 May;14(3):320–326. doi: 10.1046/j.1365-2346.1997.00130.x. [DOI] [PubMed] [Google Scholar]