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Genotoxic evaluation of bupivacaine and levobupivacaine in the Drosophila wing spot test

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Abstract

Bupivacaine and levobupivacaine are amino amide local anesthetics commonly used in medical practice. Although bupivacaine consists of a racemic mixture of S (–)-bupivacaine and R (+)-bupivacaine enantiomers, levobupivacaine is comprised of pure S (–)-bupivacaine. It has been known that levobupivacaine is preferable to bupivacaine since it may cause cardiovascular and nervous system toxicity. For determining genotoxicity of these anesthetics, we used the wing somatic mutation and recombination test in Drosophila melanogaster. Three-day-old trans-heterozygous larvae were treated with bupivacaine and levobupivacaine. Analysis of the standard crosses indicated that bupivacaine and levobupivacaine did not exhibit mutagenic or recombinogenic activity until toxic doses have been reached at the larval stage. When we examined bupivacaine and levobupivacaine in the HB cross, bupivacaine did not exhibit any genotoxicity at high concentrations (500 µg/mL), but levobupivacaine did exert genotoxicity at high concentrations (1000 µg/mL)—depending on the substantial recombinogenic effect.

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References

  • Af Ekenstam B, Egner B, Pettersson G (1957) Local anaesthetics: i. N-alkyl pyrrolidine and N-alkyl piperidine carboxylic acid amides. Acta Chem Scand 11:1183–1190

    Article  CAS  Google Scholar 

  • Albright GA (1979) Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 51:285–287

    Article  CAS  Google Scholar 

  • Barile F (2008) Principles of toxicology testing. CRC Press, Boca Raton

    Google Scholar 

  • Bishop AJ, Schiestl RH (2003) Role of homologous recombination in carcinogenesis. Exp Mol Pathol 74:94–105

    Article  CAS  Google Scholar 

  • Burlacu CL, Buggy DJ (2008) Update on local anesthetics: focus on levobupivacaine. Ther Clin Risk Manag 4:381–392

    CAS  Google Scholar 

  • Chalkiadis GA, Anderson BJ, Tay M, Bjorksten A, Kelly JJ (2005) Pharmacokinetics of levobupivacaine aftercaudalepiduraladministration in infantslessthan 3 months of age. Br J Anaesth 95:524–529

    Article  CAS  Google Scholar 

  • Dapkus D, Merrell DJ (1977) Chromosomal analysis of DDT resistance in a long-term selected population of Drosophila melanogaster. Genetics 87:685–697

    CAS  Google Scholar 

  • Drasner K (2011) Local Anesthetics. In: Miller RD, Pardo MC Jr (eds) Basics of Anesthesia. Elsevier, Philadelphia, pp 130–142

    Chapter  Google Scholar 

  • Frei H, Würgler FE (1988) Statistical methods to decide whether mutagenicity test data from Drosophila assays indicate a positive, negative or inconclusive result. Mutat Res 203:297–308

    Article  CAS  Google Scholar 

  • Frei H, Würgler FE (1996) Induction of somatic mutation and recombination by four inhibitors of eukaryotic topoisomerases assayed in the wing spot test of Drosophila melanogaster. Mutagenesis 11:315–325

    Article  CAS  Google Scholar 

  • Frei H, clements J, Howe D, Würgler FE (1992) The genotoxicity of the anti-cancer drug mitoxantrone in somatic and germ cells of Drosophila melanogaster. Mutat Res 279:21–33

    Article  CAS  Google Scholar 

  • Gantenbein M, Attolini L, Bruguerolle B, Villard PH, Puyoou F, Durand A, Lacarelle B, Hardwisgen J, Le-Treut YP (2000) Oxidative metabolism of bupivacaine into pipecolylxylidine in humans is mainly catalyzed by CYP3A. Drug Metab Dispos 28:383–385

    CAS  Google Scholar 

  • Graf U, Singer D (1992) Genotoxicity testing of promutagens in the wing somatic mutation and recombination test in Drosophila melanogaster. Rev Int Contam Ambient 8:15–27

    CAS  Google Scholar 

  • Graf U, van Schaik N (1992) Improved high bioactivation cross for the wing mutation and recombination test in Drosophila melanogaster. Mutat Res 271:59–67

    Article  CAS  Google Scholar 

  • Graf U, Würgler FE, Katz AJ, Frei H, Juon H, Hall CB, Kale PG (1984) Somatic mutation test in Drosophila melanogaster. Environ Mutagen 6:153–188

    Article  CAS  Google Scholar 

  • Graf U, van Schaik N, Pacella R (1991) Improved “High Bioactivation” cross for the SMART wing assay. Drosoph Inf Serv 70:247–248

    Google Scholar 

  • Graf U, Abraham SK, Guzmán-Rincón J, Würgler FE (1998) Antigenotoxicity studies in Drosophila melanogaster. Mut Res 402:203–209

    Article  CAS  Google Scholar 

  • Gürbüzel M, Oral E, Kizilet H, Halici Z, Gulec M (2012) Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster. Mutat Res 748:17–20

    Article  Google Scholar 

  • Gürbüzel M, Capoğlu I, Kızılet H, Halıcı Z, Ozçiçek F, Demirtaş L (2014) Genotoxic evaluation of two oral antidiabetic agents in the Drosophila wing spot test. Toxicol Ind Health 30:376–383

    Article  Google Scholar 

  • Guzmán Rincón J, Graf U (1995) Drosophila melanogaster somatic mutation and recombination test as a biomonitor. In: Butterworth FM, Corkum LD, Guzmán Rincón J (eds) Biomonitors and biomarkers as indicators of environmental change. Plenum Press, New York, pp 169–181

  • Hagiwara M, Watanabe E, Barrett JC, Tsutsui T (2006) Assessment of genotoxicity of 14 chemical agents used in dental practice: ability to induce chromosome aberrations in Syrian hamster embryo cells. Mutat Res 603:111–120

    Article  CAS  Google Scholar 

  • Hällström I, Blanck A, Atuma S (1984) Genetic variation in cytochrome P-450 and xenobiotic metabolism in Drosophila melanogaster. Biochem Pharmacol 33:13–20

    Article  Google Scholar 

  • Huang YF, Pryor ME, Mather LE, Veering BT (1998) Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep. Anesth Analg 86:797–804

    Article  CAS  Google Scholar 

  • Idaomar M, El Hamss R, Bakkali F, Mezzoug N, Zhiri A, Baudoux D, Muñoz-Serrano A, Liemans V, Alonso-Moraga A (2002) Genotoxicity and antigenotoxicity of some essential oils evaluated by wing spot test of Drosophila melanogaster. Mutat Res 513:61–68

    Article  CAS  Google Scholar 

  • Karadeniz A, Kaya B, Savaş B, Topcuoğlu ŞF (2011) Effects of two plant growth regulators, indole-3-acetic acid and β-naphthoxyacetic acid, on genotoxicity in Drosophila SMART assay and on proliferation and viability of HEK293 cells from the perspective of carcinogenesis. Toxicol Ind Health 27:840–848

    Article  CAS  Google Scholar 

  • Kastenbaum MA, Bowman KO (1970) Tables for determining the statistical significance of mutation frequencies. Mutat Res 9:527–549

    Article  CAS  Google Scholar 

  • Kaya B, Marcos R, Yanikoğlu A, Creus A (2004) Evaluation of the genotoxicity of four herbicides in the wing spot test of Drosophila melanogaster using two different strains. Mutat Res 557:53–62

    Article  CAS  Google Scholar 

  • Kayukawa E, Kikuchi S, Tsutsui T (1988) Cytotoxicity, genotoxicity and carcinogenicity of local anesthetics to cultured Syrian hamster embryo cells. Shiqaku 76:941–962

    CAS  Google Scholar 

  • Koksal PM, Gürbüzel M (2015) Analysis of genotoxic activity of ketamine and rocuronium bromide using the somatic mutation and recombination test in Drosophila melanogaster. Environ Toxicol Pharmacol 39:628–634

  • Kulbacka J, Bar J, Chwilkowska A, Dumanska M, Drag-Zalesinska M, Wysocka T, Stach K, Bednarz I, Lugowski M, Marcinkowska A, Gamian A, Saczko J (2009) Oxidative modulation of Marcaine and lekoptin in H9C2 rat myoblasts. Acta Pharmacol Sin 30:184–192

    Article  CAS  Google Scholar 

  • Leone S, Di Cianni S, Casati A, Fanelli G (2008) Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. Acta Biomed 79:92–105

    CAS  Google Scholar 

  • Leuschner J, Leblanc D (1999) Studies on the toxicological profile of the local anaesthetic articaine. Arzneimittelforschung 49:126–132

    CAS  Google Scholar 

  • Lindsley DL, Zimm GG (1992) The genome of Drosophila melanogaster. Academic Press, San Diego

    Google Scholar 

  • Mendola C, Ferrante D, Oldani E, Cammarota G, Cecci G, Vaschetto R, Della Corte F (2009) Thoracic epidural analgesia in post-thoracotomy patients: comparison of three different concentrations of levobupivacaine and sufentanil. Br J Anaesth 102:418–423

    Article  CAS  Google Scholar 

  • Nai GA, de Oliveira MC, de Oliveira TG, Pereira LF, Soares ND, Silva PG (2015) Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats. Braz J Anesthesiol 65:21–26

    Article  Google Scholar 

  • Osaba L, Aguirre A, Alonso A, Graf U (1999) Genotoxicity testing of six insecticides in two crosses of the Drosophila wing spot test. Mutat Res 439:49–61

    Article  CAS  Google Scholar 

  • Pacella RE (1993) Genotoxicity of mycotoxins in an improved Drosophila wing spot test and other short-term tests, PhD thesis. Witwatersrand University, Johannesburg

  • Pacella RE, van Schaik N, Graf U (1996) New “high bioactivation” cross for the SMART wing assay. Drosoph Inf Serv 77:152–153

  • Schneider LE, do Amaral VS, Dihl RR, Lehmann M, Reguly ML, de Andrade HHR (2009) Assessment of genotoxicity of Lidocaine®, Prilonest® and Septanest® in the Drosophila wing-spot test. Food Chem Toxicol 47:205–208

    Article  CAS  Google Scholar 

  • Scott DB, Lee A, Fagan D, Bowler GM, Bloomfield P, Lundh R (1989) Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 69:563–569

    CAS  Google Scholar 

  • Spanó MA, Frei H, Würgler FE, Graf U (2001) Recombinagenic activity of four compounds in the standard and high bioactivation crosses of Drosophila melanogaster in the wing spot test. Mutagenesis 16:385–394

    Article  Google Scholar 

  • Tijet N, Helvig C, Feyereisen R (2001) The cytochrome P450 gene superfamily in Drosophila melanogaster: annotation, intron-exon organization and phylogeny. Gene 262:189–198

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was partially supported by a grant from the Research Fund of Erzincan, University (Project No. 11.02.12).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biology, Faculty of Arts and Sciences, Erzincan University, 24100, Erzincan, Turkey

    Mehmet Gürbüzel, Ugur Karaca & Nermin Karayilan

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  1. Mehmet Gürbüzel
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  2. Ugur Karaca
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  3. Nermin Karayilan
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Correspondence to Mehmet Gürbüzel.

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Gürbüzel, M., Karaca, U. & Karayilan, N. Genotoxic evaluation of bupivacaine and levobupivacaine in the Drosophila wing spot test. Cytotechnology 68, 979–986 (2016). https://doi.org/10.1007/s10616-015-9852-2

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  • DOI: https://doi.org/10.1007/s10616-015-9852-2

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