Skip to main content

Advertisement

Log in

Direct assessment of the antioxidant properties of midazolam by electron spin resonance spectroscopy

  • Short Communication
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Some antioxidant anesthetics directly inhibit lipid peroxidation mediated via the generation of reactive oxygen species (ROS). To date, the scavenging effects of midazolam on ROS have not been directly assessed. We investigated the inhibitory effect of midazolam on ROS [hydroxyl radical (HO·) and superoxide (O ·–2 )] by in vitro X-band electron spin resonance with the spin-trapping agent 5,5-dimethyl-1-pyrroline-N-oxide. Our results indicated that HO· and O ·–2 were not affected by midazolam at clinically relevant concentrations, but were directly scavenged by midazolam at high concentrations (i.e., >4.6 and >1.5 mM, respectively).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

References

  1. Saito A, Maier CM, Narasimhan P, Nishi T, Song YS, Yu F, Liu J, Lee YS, Nito C, Kamada H, Dodd RL, Hsieh LB, Hassid B, Kim EE, Gonzalez M, Chan PH. Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Mol Neurobiol. 2005;31:105–16.

    Article  PubMed  CAS  Google Scholar 

  2. Ajamieh H, Merino N, Candelario-Jalil E, Menendez S, Martinez-Sanchez G, Re L, Giuliani A, Leon OS. Similar protective effect of ischaemic and ozone oxidative preconditionings in liver ischaemia/reperfusion injury. Pharmacol Res. 2002;45:333–9.

    Article  PubMed  CAS  Google Scholar 

  3. Poon HF, Calabrese V, Scapagnini G, Butterfield DA. Free radicals and brain aging. Clin Geriatr Med. 2004;20:329–59.

    Article  PubMed  Google Scholar 

  4. Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother. 2004;58:39–46.

    Article  PubMed  CAS  Google Scholar 

  5. Wilson JX, Gelb AW. Free radicals, antioxidants, and neurologic injury: possible relationship to cerebral protection by anesthetics. J Neurosurg Anesthesiol. 2002;14:66–79.

    Article  PubMed  Google Scholar 

  6. Chikutei K, Oyama TM, Ishida S, Okano Y, Kobayashi M, Matsui H, Horimoto K, Nishimura Y, Ueno SY, Oyama Y. Propofol, an anesthetic possessing neuroprotective action against oxidative stress, promotes the process of cell death induced by H2O2 in rat thymocytes. Eur J Pharmacol. 2006;540:18–23.

    Article  PubMed  CAS  Google Scholar 

  7. Cuadrado A, Solares G, Gonzalez S, Sanchez B, Armijo JA. Propofol concentrations in whole blood: influence of anticoagulants and storage time. Methods Find Exp Clin Pharmacol. 1998;20:297–300.

    Article  PubMed  CAS  Google Scholar 

  8. De La Cruz JP, Villalobos MA, Sedeno G, Sanchez De La Cuesta F. Effect of propofol on oxidative stress in an in vitro model of anoxia-reoxygenation in the rat brain. Brain Res. 1998;800:136–44.

    Article  PubMed  Google Scholar 

  9. Kobayashi K, Yoshino F, Takahashi SS, Todoki K, Maehata Y, Komatsu T, Yoshida K, Lee MC. Direct assessments of the antioxidant effects of propofol medium chain triglyceride/long chain triglyceride on the brain of stroke-prone spontaneously hypertensive rats using electron spin resonance spectroscopy. Anesthesiology. 2008;109:426–35.

    Article  PubMed  CAS  Google Scholar 

  10. Tsuchiya H. Structure-specific membrane-fluidizing effect of propofol. Clin Exp Pharmacol Physiol. 2001;28:292–9.

    Article  PubMed  CAS  Google Scholar 

  11. Lee C, Miura K, Liu X, Zweier JL. Biphasic regulation of leukocyte superoxide generation by nitric oxide and peroxynitrite. J Biol Chem. 2000;275:38965–72.

    Article  PubMed  CAS  Google Scholar 

  12. Kiyose M, Lee CI, Okabe E. Inhibition of skeletal sarcoplasmic reticulum Ca2+-ATPase activity by deferoxamine nitroxide free radical. Chem Res Toxicol. 1999;12:137–43.

    Article  PubMed  CAS  Google Scholar 

  13. Yoshino F, Shoji H, Lee MC. Vascular effects of singlet oxygen (1O2) generated by photo-excitation on adrenergic neurotransmission in isolated rabbit mesenteric vein. Redox Rep. 2002;7:266–70.

    Article  PubMed  CAS  Google Scholar 

  14. Ogasawara Y, Namai T, Yoshino F, Lee MC, Ishii K. Sialic acid is an essential moiety of mucin as a hydroxyl radical scavenger. FEBS Lett. 2007;581:2473–7.

    Article  PubMed  CAS  Google Scholar 

  15. Guo Q, Zhao B, Li M, Shen S, Xin W. Studies on protective mechanisms of four components of green tea polyphenols against lipid peroxidation in synaptosomes. Biochim Biophys Acta. 1996;1304:210–22.

    PubMed  CAS  Google Scholar 

  16. Ohsugi M, Fan W, Hase K, Xiong Q, Tezuka Y, Komatsu K, Namba T, Saitoh T, Tazawa K, Kadota S. Active-oxygen scavenging activity of traditional nourishing-tonic herbal medicines and active constituents of Rhodiola sacra. J Ethnopharmacol. 1999;67:111–9.

    Google Scholar 

  17. Sakurai K, Sasabe H, Koga T, Konishi T. Mechanism of hydroxyl radical scavenging by rebamipide: identification of mono-hydroxylated rebamipide as a major reaction product. Free Radic Res. 2004;38:487–94.

    Article  PubMed  CAS  Google Scholar 

  18. Buettner GR. Spin trapping: ESR parameters of spin adducts. Free Radic Biol Med. 1987;3:259–303.

    Article  PubMed  CAS  Google Scholar 

  19. Cheng YJ, Wang YP, Chien CT, Chen CF. Small-dose propofol sedation attenuates the formation of reactive oxygen species in tourniquet-induced ischemia–reperfusion injury under spinal anesthesia. Anesth Analg. 2002;94:1617–20.

    Google Scholar 

  20. Engelhard K, Werner C, Eberspacher E, Pape M, Stegemann U, Kellermann K, Hollweck R, Hutzler P, Kochs E. Influence of propofol on neuronal damage and apoptotic factors after incomplete cerebral ischemia and reperfusion in rats: a long-term observation. Anesthesiology. 2004;101:912–7.

    Article  PubMed  CAS  Google Scholar 

  21. Yasuda T, Takahashi S, Matsuki A. Tumor necrosis factor-alpha reduces ketamine- and propofol-induced anesthesia time in rats. Anesth Analg. 2002;95:952–5.

    Google Scholar 

  22. Sayin MM, Ozatamer O, Tasoz R, Kilinc K, Unal N. Propofol attenuates myocardial lipid peroxidation during coronary artery bypass grafting surgery. Br J Anaesth. 2002;89:242–6.

    Article  PubMed  CAS  Google Scholar 

  23. Erol U, Gurdal M, Erol A, Aslan R, Konukoglu D, Onmus H. Is midazolam effective as an antioxidant in preventing reperfusion injury in rat kidney? Int Urol Nephrol. 2002;34:121–7.

    Article  PubMed  CAS  Google Scholar 

  24. Tsuchiya M, Asada A, Maeda K, Ueda Y, Sato EF, Shindo M, Inoue M. Propofol versus midazolam regarding their antioxidant activities. Am J Respir Crit Care Med. 2001;163:26–31.

    PubMed  CAS  Google Scholar 

  25. Lee MC, Kawai Y, Shoji H, Yoshino F, Miyazaki H, Kato H, Suga M, Kubota E. Evidence of reactive oxygen species generation in synovial fluid from patients with temporomandibular disease by electron spin resonance spectroscopy. Redox Rep. 2004;9:331–6.

    Article  PubMed  CAS  Google Scholar 

  26. Komatsu T, Lee MC, Miyagi A, Shoji H, Yoshino F, Maehata Y, Maetani T, Kawamura Y, Ikeda M, Kubota E. Reactive oxygen species generation in gingival fibroblasts of Down syndrome patients detected by electron spin resonance spectroscopy. Redox Rep. 2006;11:71–7.

    Article  PubMed  CAS  Google Scholar 

  27. Murphy PG, Myers DS, Davies MJ, Webster NR, Jones JG. The antioxidant potential of propofol (2,6-diisopropylphenol). Br J Anaesth. 1992;68:613–8.

    Article  PubMed  CAS  Google Scholar 

  28. Kagan VE, Serbinova EA, Packer L. Generation and recycling of radicals from phenolic antioxidants. Arch Biochem Biophys. 1990;280:33–9.

    Article  PubMed  CAS  Google Scholar 

  29. Kagan VE, Tsuchiya M, Serbinova E, Packer L, Sies H. Interaction of the pyridoindole stobadine with peroxyl, superoxide and chromanoxyl radicals. Biochem Pharmacol. 1993;45:393–400.

    Article  PubMed  CAS  Google Scholar 

  30. Chan PH. Role of oxidants in ischemic brain damage. Stroke. 1996;27:1124–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Supported by grants from High-Tech Research Center Project of Kanagawa Dental College, Yokosuka, Kanagawa, Japan, and grants-in-aid for Scientific Research from the Japanese Ministry of Education, Science, and Culture, Tokyo (19592371) and (21792036).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Masaichi-Chang-il Lee.

Additional information

M. Hata and K. Kobayashi contributed equally to this work.

About this article

Cite this article

Hata, M., Kobayashi, K., Yoshino, F. et al. Direct assessment of the antioxidant properties of midazolam by electron spin resonance spectroscopy. J Anesth 25, 765–769 (2011). https://doi.org/10.1007/s00540-011-1184-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-011-1184-6

Keywords

Navigation