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Molecular Biology Reports

, Volume 46, Issue 3, pp 2819–2827 | Cite as

Anesthesia may alter mRNA expression of certain wound healing-associated genes in dermal wound environment of the rats

  • Muhammed Akif Altun
  • Ahmet OzaydinEmail author
  • Hülya Arkan
  • Suleyman Demiryas
  • Fahri Akbas
  • Nurten Bahtiyar
  • Ilhan Onaran
Original Article
  • 117 Downloads

Abstract

Some anesthetics including ketamine/xylazine and thiopental have been shown to alter the expression of genes related with inflammatory cytokines and chemokines in previous studies unassociated with wound healing, arising the question of whether commonly used anesthetics in wound healing models could interfere with the transcriptional responses of the genes associated with skin wound healing. The gene expression profile in wound biopsies of rats who received widely used anesthetics doses of intraperitoneal ketamine/xylazine (50 mg/kg and 10 mg/kg) or thiopental (50 mg/kg) in comparison with control rats was analyzed by monitoring the expression of genes effective on various phases of wound healing. The expression levels of 84 genes were determined on 3rd, 7th and 14th days of post-wounding using a qPCR array system. Of the genes either up or downregulated fivefolds or more, three (Egf, Col5a1 and Cxcl3) and two (Tgfa and Il2) genes were found to be the most responsive ones to ketamine/xylazine or thiopental anesthesia respectively in a period of 14 days after correction for multiple testing. However, up to 22 and 24 genes for ketamine/xylazine and thiopental were found to be differentially expressed in the same period without correction for multiple-comparisons testing (p < 0.05). In conclusion, our data suggest that ketamine/xylazine and thiopental may alter the transcriptional responses of some genes associated with wound healing in rats. We strongly suggest to consider the possible alteration effect of these anesthetics on gene expression in animal models of dermal wound healing.

Keywords

Ketamine/xylazine Thiopental Anesthetics Wound healing Gene expression 

Notes

Acknowledgements

This work was supported by the Research Fund of the University of Istanbul, Project number: 156.2015-YL-35/2709.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Cooper L, Johnson C, Burslem F et al (2005) Wound healing and inflammation genes revealed by array analysis of ‘macrophageless’ PU.1 null mice. Genome Biol 6(1):R5CrossRefGoogle Scholar
  2. 2.
    Deonarine K, Panelli MC, Stashower ME et al (2007) Gene expression profiling of cutaneous wound healing. J Transl Med 5:11CrossRefGoogle Scholar
  3. 3.
    Alkafafy M, Montaser M, Ei-Shazly SA et al (2012) Ethanolic extract of sharah, Plectranthus aegyptiacus, enhances healing of skin wound in rats. Acta Histochem 116:627–638CrossRefGoogle Scholar
  4. 4.
    Heise R, Skazik C, Marquardt Y et al (2012) Dexpanthenol modulates gene expression in skin wound healing in vivo. Skin Pharmacol Physiol 25:241–248CrossRefGoogle Scholar
  5. 5.
    Polat E, Aksoz I, Arkan H et al (2014) Gene expression profiling of Lucilia sericata larvae extraction/secretion-treated skin wounds. Gene 550:223–229CrossRefGoogle Scholar
  6. 6.
    Romana-Souza B, Santos JS, Bandeira LG et al (2016) Selective inhibition of COX-2 improves cutaneous wound healing of pressure ulcers in mice through reduction of iNOS expression. Life Sci 153:82–92CrossRefGoogle Scholar
  7. 7.
    Velnar T, Bailey T, Smrkoli V (2009) The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 37:1528–1542CrossRefGoogle Scholar
  8. 8.
    Helmer KS, Cui Y, Chang L et al (2003) Effects of ketamine/xylazine on expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclo-oxygenase-2 in rat gastric mucosa during endotoxemia. Shock 20:63–69CrossRefGoogle Scholar
  9. 9.
    Ichiyama T, Nishikawa M, Lipton JM et al (2001) Thiopental inhibits NF-κB activation in human glioma cells and experimental brain inflammation. Brain Res 911:56–61CrossRefGoogle Scholar
  10. 10.
    Sakai T, Ichiyama T, Whitten CW et al (2000) Ketamine suppresses endotoxin-induced NF-κB expression. Can J Anaesth 47:1019–1024CrossRefGoogle Scholar
  11. 11.
    Schneemilch CE, Ittenson A, Ansorge S et al (2005) Effect of 2 anesthetic techniques on the postoperative proinflammatory and anti-inflammatory cytokine response and cellular immune function to minor surgery. J Clin Anesth 17:517–527CrossRefGoogle Scholar
  12. 12.
    Shi Q, Guo L, Patterson TA et al (2010) Gene expression profiling in the developing rat brain exposed to ketamine. Neuroscience 166:852–863CrossRefGoogle Scholar
  13. 13.
    Takala RSK, Soukka H, Salo MS et al (2006) Gene expression of pulmonary cytokines after sevoflurane or thiopentone anaesthesia in pigs. Acta Anaesthesiol Scand 50:163–167CrossRefGoogle Scholar
  14. 14.
    Chang Y, Chen TL, Sheu JR et al (2005) Suppressive effects of ketamine on macrophage functions. Toxicol Appl Pharm 204:27–35CrossRefGoogle Scholar
  15. 15.
    Schwer CI, Lehane C, Guelzow T et al (2013) Thiopental inhibits global protein synthesis by repression of Eukaryotic elongation factor 2 and protects from hypoxic neuronal cell death. PLoS ONE 8:e77258CrossRefGoogle Scholar
  16. 16.
    Chvapil M, Hameroff SR, O’Dea K et al (1979) Local anesthetics and wound healing. J Surg Res 27:367–371CrossRefGoogle Scholar
  17. 17.
    Danzi MCMD, Avison DL, Bixby JL et al (2016) Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healing-associated genes. Neural Regen Res 11:144–149CrossRefGoogle Scholar
  18. 18.
    Hanci V, Hakimoglu S, Ozacmak H et al (2012) Comparison of the effects of bupivacaine, lidocaine, and tramadol infiltration on wound healing in rats. Rev Bras Anestesiol 62:799–810CrossRefGoogle Scholar
  19. 19.
    Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108CrossRefGoogle Scholar
  20. 20.
    Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57CrossRefGoogle Scholar
  21. 21.
    Guo S, DiPietro LA (2010) Factors affecting wound healing. J Dent Res 89:219–229CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Medical Biology, Cerrahpasa Faculty of MedicineIstanbul University-CerrahpasaIstanbulTurkey
  2. 2.Department of General Surgery, Cerrahpasa Faculty of MedicineIstanbul University-CerrahpasaIstanbulTurkey
  3. 3.Department of Medical Biology, Faculty of MedicineBezmialem Vakif UniversityIstanbulTurkey
  4. 4.Department of Biophysics, Cerrahpasa Faculty of MedicineIstanbul University-CerrahpasaIstanbulTurkey

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