Research Article
BibTex RIS Cite

Micronucleus evaluation of remifentanil exposure

Year 2025, Volume: 29 Issue: 1, 177 - 181

Abstract

Remifentanil is an analgesic used in clinical settings. However, its potential genotoxic effects on lymphocytes have not been extensively investigated. This research aimed to assess the dose-dependent impact of remifentanil on micronucleus formation in healthy human lymphocytes after exposure of 24 and 48 hours, comparing them with spontaneous and positive controls. Lymphocytes from healthy individuals were exposed to remifentanil at concentrations of 50, 150, 250, and 350 µg/mL for 24 and 48 hours. Micronucleus formation incidence was evaluated and compared with both spontaneous control and positive control groups. Remifentanil elevated the formation of micronucleus in a dose dependent manner as compared to the spontaneous control values, however, this increse was not significant statistically. This increase was significant at only the highest (350 µg/mL) concentration. Micronucleus (MN) frequency was statistically significant at only the 350 µg/mL dose of remifentanil when compared with the spontaneous. The value of cell proliferation index (CPI) was not decreased by remifentanil when compared to spontaneous control. Decrease in CPI values provide information about the genotoxicity of the doses. Evaluation of remifentanil research should extend beyond in vitro methods to include in vivo approaches applied to individuals with frequent exposure, particularly concerning chromosomal abnormalities.

References

  • [1] Egan TD, Lemmens HJ, Fiset P, Hermann D J, Muir K T, Stanski DR, Shafer S L. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology. 1993; 79(5): 881–892. https://doi.org/10.1097/00000542-199311000-00004
  • [2] Shafer SL. The pharmacology of anesthetic drugs in elderly patients. Anesthesiol Clin North Am. 18(1): 1–29. https://doi.org/10.1016/s0889-8537(05)70146-2
  • [3] Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006; 104(3): 570–587. https://doi.org/10.1097/00000542-200603000-00025
  • [4] Mpountoukas P, Pantazaki A, Kostareli E, Christodoulou P, Kareli D, Poliliou S, Mourelatos C, Lambropoulou V, Lialiaris T. Cytogenetic evaluation and DNA interaction studies of the food colorants amaranth, erythrosine and tartrazine. Food Chem Toxicol. 2010; 48(10): 2934–2944. https://doi.org/10.1016/j.fct.2010.07.030
  • [5] Kılıc M, Tuylu BA. An in vitro investigation of genotoxic effects of dexketoprofen trometamol on healthy human lymphocytes. Drug Chem Toxicol. 2000; 43(2): 174–181. https://doi.org/10.1080/01480545.2018.1485690
  • [6] Güzel Bayülken D, Ayaz Tüylü B, Sinan H, Sivas H. Investigation of genotoxic effects of paraben in cultured human lymphocytes. Drug Chem Toxicol. 2000; 42(4): 349–356. https://doi.org/10.1080/01480545.2017.1414834
  • [7] Kirsch-Volders M, Sofuni T, Aardema M, Albertini S, Eastmond D, Fenech M, Ishidate M, Jr Kirchner S, Lorge E, Morita T, Norppa H, Surrallés J, Vanhauwaert A, Wakata A. Report from the in vitro micronucleus assay working group. Mutat Res. 2003; 540(2): 153–163. https://doi.org/10.1016/j.mrgentox.2003.07.005
  • [8] Beynek N, Uluçam G, Tüylü BA, Zeytinoğlu H, Benkli K. Synthesis and characterization of a new macrocyclic ligand and its copper (II), cadmium (II), and lead (II) complexes: Genotoxic activity of these complexes in cultured human lymphocytes. Drug Chem Toxicol. 2007; 30(4): 399–410. https://doi.org/10.1080/01480540701522601
  • [9] Fenech M, Chang W P, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E. HUMN project: Detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res. 2003; 534(1-2): 65–75. https://doi.org/10.1016/s1383-5718(02)00249-8
  • [10] Noel S, Kasinathan M, Rath S K. Evaluation of apigenin using in vitro cytochalasin blocked micronucleus assay. Toxicol in vitro. 2006; 20(7): 1168–1172. https://doi.org/10.1016/j.tiv.2006.03.007
  • [11] Albertini R J, Anderson D, Douglas G R, Hagmar L, Hemminki K, Merlo F, Natarajan A T, Norppa H, Shuker D E, Tice R, Waters MD, Aitio A. IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety. Mutat Res. 2000; 463(2): 111–172. https://doi.org/10.1016/s1383 5742(00)00049-1
  • [12] Kirsch-Volders M., Elhajouji A., Cundari E., Van Hummelen P. The in vitro micronucleus test: a multi-endpoint assay to detect simultaneously mitotic delay, apoptosis, chromosome breakage, chromosome loss and non disjunction. Mutat Res. 1997; 392(1-2): 19–30. https://doi.org/10.1016/s0165-1218(97)00042-6
  • [13] Nersesyan A, Perrone E, Roggieri P, Bolognesi C. Genotoxic action of cycloplatam, a new platinum antitumor drug, on mammalian cells in vivo and in vitro. Chemotherapy. 2003; 49(3): 132–137. https://doi.org/10.1159/000070619
  • [14] Fimognari C, Berti, F, Iori R, Cantelli-Forti G, Hrelia P. Micronucleus formation and induction of apoptosis by different isothiocyanates and a mixture of isothiocyanates in human lymphocyte cultures. Mutat Res. 2005; 582(1-2): 1–10. https://doi.org/10.1016/j.mrgentox.2004.11.019
  • [15] Lerda D, Biaggi Bistoni M, Peralta N, Ychari S, Vazquez M, Bosio G. Fumonisins in foods from Cordoba (Argentina), presence and genotoxicity. Food Chem Toxicol. 2005; 43(5): 691–698. https://doi.org/10.1016/j.fct.2004.12.019
  • [16] Fenech M. The in vitro micronucleus technique. Mutat Res. 2000; 455(1-2): 81–95. https://doi.org/10.1016/s0027 5107(00)00065-8
  • [17] de Carvalho LR, Vieira DP. Evaluation of genotoxic potential of peptides used in nuclear medicine (PSMA -617 and -11, and ubiquicidine 29-41) using a flow-cytometric, semi-automated analysis of micronuclei frequency in cell cultures. Toxicol Rep. 2020;7: 304–316. https://doi.org/10.1016/j.toxrep.2020.02.003
  • [18] Garibay-Garcia J, Mejia-Sanchez F, Ramírez-San-Juan E, Flores-Merino MV, Castillo-CadenaJ. Genotoxic and cytotoxic damage by cyclophosphamide and adriamycin as a response to treatment in breast cancer patients: Pilot study. J Cancer Ther. 2015; 6: 163-168. http://dx.doi.org/10.4236/jct.2015.62018
  • [19] Fenech M, Crott JW. Micronuclei, nucleoplasmic bridges and nuclear buds induced in folic acid deficient human lymphocytes-evidence for breakage-fusion-bridge cycles in the cytokinesis-block micronucleus assay. Mutat Res. 2002; 504(1-2): 131–136. https://doi.org/10.1016/s0027-5107(02)00086-6
  • [20] Fenech M. The lymphocyte cytokinesis-block micronucleus cytome assay and its application in radiation biodosimetry. Health Phys. 2010; 98(2): 234–243. https://doi.org/10.1097/HP.0b013e3181b85044
  • [21] Thomas P, Holland N, Bolognesi C, Kirsch-Volders M, Bonassi S, Zeiger E, Knasmueller S, Fenech M. Buccal micronucleus cytome assay. Nat Protoc. 2009; 4(6): 825–837. https://doi.org/10.1038/nprot.2009.53
  • [22] Wu J, Lyons GH, Graham RD, Fenech MF. The effect of selenium, as selenomethionine, on genome stability and cytotoxicity in human lymphocytes measured using the cytokinesis-block micronucleus cytome assay. Mutagenesis. 2009; 24(3): 225–232. https://doi.org/10.1093/mutage/gen074
There are 22 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Articles
Authors

Öge Başoğlan Artagan

Publication Date
Submission Date December 27, 2023
Acceptance Date February 12, 2024
Published in Issue Year 2025 Volume: 29 Issue: 1

Cite

APA Başoğlan Artagan, Ö. (n.d.). Micronucleus evaluation of remifentanil exposure. Journal of Research in Pharmacy, 29(1), 177-181.
AMA Başoğlan Artagan Ö. Micronucleus evaluation of remifentanil exposure. J. Res. Pharm. 29(1):177-181.
Chicago Başoğlan Artagan, Öge. “Micronucleus Evaluation of Remifentanil Exposure”. Journal of Research in Pharmacy 29, no. 1 n.d.: 177-81.
EndNote Başoğlan Artagan Ö Micronucleus evaluation of remifentanil exposure. Journal of Research in Pharmacy 29 1 177–181.
IEEE Ö. Başoğlan Artagan, “Micronucleus evaluation of remifentanil exposure”, J. Res. Pharm., vol. 29, no. 1, pp. 177–181.
ISNAD Başoğlan Artagan, Öge. “Micronucleus Evaluation of Remifentanil Exposure”. Journal of Research in Pharmacy 29/1 (n.d.), 177-181.
JAMA Başoğlan Artagan Ö. Micronucleus evaluation of remifentanil exposure. J. Res. Pharm.;29:177–181.
MLA Başoğlan Artagan, Öge. “Micronucleus Evaluation of Remifentanil Exposure”. Journal of Research in Pharmacy, vol. 29, no. 1, pp. 177-81.
Vancouver Başoğlan Artagan Ö. Micronucleus evaluation of remifentanil exposure. J. Res. Pharm. 29(1):177-81.