TSitologiya i Genetika 2020, vol. 54, no. 4, 63-72
Cytology and Genetics 2020, vol. 54, no. 4, 333–340, doi: https://www.doi.org/10.3103/S0095452720040027

Molecular, genetic and cytological specificities of healing under alkaline esophageal burns and at the administration of melanin

Chornenka N.M., Raetska Ya.B., Dranitsina A.S., Kalmukova O.O., Beregova T.V., Dzerzhynsky M.E., Savchuk O.M., Ostapchenko L.I.

  • Scientific Center «Institute of Biology and Medicine», Taras Shevchenko National University of Kyiv, 01601, Kyiv, Volodymyrska street 64/13

SUMMARY. Educational and 3 We have shown decreased expression of the gene involved in the synthesis of collagen Col2a1 in the blood and esophageal mucus in the alkaline esophageal burn of the 2nd degree (AEB 2). When melanin was administered, the level of expression of the Col2a1 gene in the blood and esophagus tissues increased as compared to those in AEB 2. During the histological study, we have determined the intensity of deposition of collagen fibers, and also have measured the index of stenosis of the esophagus and assessed the effect of melanin on the healing processes: less pronounced formation of collagen fibers in damaged esophagus tissues. It was found that in the serum of blood and esophageal mucosa, the level of pro-inflammatory cytokine IL-6 was increased and the level of anti-inflammatory cytokine IL-10 was decreased. After the administration of melanin, the normalization of the content of cytokines was noted in comparison with the indicators at AEB 2, indicating the anti-inflammatory and anti-fibrotic properties of this substance and demonstrating the prospect of the use of melanin as a substance contributing to the healing of chemical burn of the esophagus without the formation of a pathological scar.

Keywords: alkaline burn of the esophagus, fibrosis, expression of Col2a1 genes, cytokines, melanin

TSitologiya i Genetika
2020, vol. 54, no. 4, 63-72

Current Issue
Cytology and Genetics
2020, vol. 54, no. 4, 333–340,
doi: 10.3103/S0095452720040027

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References

1. Digtyar, V.A, Barsuk, O.M., Kaminska, M.O., Glad-kyi, O.P., and Galagan, A.A., Treatment of chemical burns of the esophagus in children, Paediatr. Surg., 2017, vol. 3 (56), no. 3, pp. 54–56. https://doi.org/10.1016/j.legalmed.2013.10.00210.15574/PS.2017.56.54

2. Dash, S., Bhojani, J., and Sharma, S., A rare case of anal and perianal chemical burn in a child due to potassium permanganate crystals drug, Saf. Case Rep., 2018, vol. 5, pp. 10–15.https://doi.org/10.1016/j.legalmed.2013.10.002:10.1007/s40800-018-0072-5

3. Nakajima, Y., Nakano, Y., Fuwano, S., Hayashi, N., Hiratoko, Y., Kinoshita, A., Miyahara, M., Mochizuki, T., Nishino, K., Tsuruhara, Y., Yokokawa, Y., Iuchi, T., Kon, Y., Mukai, K., Kitayama, Y., Murakado, N., Okuwa, M., and Nakatani, T., Effects of three types of Japanese honey on full-thickness wound in mice, Evid.-Based Complement. Altern. Med., 2013, vol. 2013, p. 504 537.https://doi.org/10.1155/2013/504537

4. Neub, A., Houdek, P., Ohnemus, U., Moll, I., and Brandner, J.M., Biphasic regulation of AP-1 subunits during human epidermal wound healing, J. Invest. Dermatol., 2007, vol. 127, no. 10, pp. 2453–2462.

5. Al-Waili, N.S., Salom, K., and Al-Ghamdi, A.A., Honey for wound healing, ulcers, and burns; data supporting its use in clinical practice, Sci. World J., 2011, vol. 11, pp. 766–787.https://doi.org/10.1100/tsw.2011.78 https://doi.org/10.1016/j.legalmed.2013.10.002

6. Nayak, B.S. and Pinto Pereira, L.M., Catharanthus roseus flower extract has wound-healing activity in Sprague Dawley rats, BMC Compl. Altern. Med., 2006, vol. 6, p. 41. https://doi.org/10.1186/1472-6882-6-41

7. Rawat, S. and Gupta, A., Development and study of wound healing activity of an ayurvedic formulation, Asian J. Pharmac. Sci., 2011, vol. 1, no. 1, pp. 26–28.

8. Reinke, J.M. and Sorg, H., Wound repair and regeneration, Eur. Surg. Res., 2012, vol. 49, pp. 35–43. https://doi.org/10.1159/000339613

9. Werner, S., Krieg, T., and Smola, H., Keratinocyte-fibroblast interactions in wound healing, J. Invest. Dermatol., 2007, vol. 127, pp. 998–1008. https://doi.org/10.1038/sj.jid.5700786

10. Zhou, L., Xiao, X., Li, S., Jia, X., Wang, P., Sun, W., Zhang, F., Li, J., Li, T., and Zhang, Q., Phenotypic characterization of patients with early-onset high myopia due to mutations in COL2A1 or COL11A1: why not Stickler syndrome?, Mol. Vis., 2018, vol. 24, pp. 560–573. PMID: 30181686

11. Dikaiakou, E., Vlachopapadopoulou, E.A., and Manolakos, E., Identification of an autosomal dominant mutation in the COL2A1 gene leading to spondyloepiphyseal dysplasia congenita in a Greek family, Mol. Syndromol., 2019, vol. 9, no. 5, pp. 241–246. https://doi.org/10.1159/000492190

12. Abaev, Yu.K., The biology of healing acute and chronic wounds, Med. News, 2003, vol. 6, pp. 3–10.

13. Widgerow, A.D., Cellular/extracellular matrix cross talk in scar evolution and control, Wound Repair Regen., 2011, vol. 19, no. 2, pp. 117–133. https://doi.org/10.1111/j.1524-475X.2010.00662.x

14. Salih, E., Afaf, K., and Mohamed Anwar, K., Pharmacological properties of melanin and its function in health, Basic Clin. Pharmacol. Toxicol., 2017, vol. 120, no. 6, pp. 515–522. https://doi.org/10.1111/bcpt.12748

15. Kunwar, A., Adhikary, B., Jayakumar, S., and Barik, A., Melanin, a promising radioprotector: mechanisms of actions in a mice model, Toxicol. Appl. Pharmacol., 2012, vol. 264, pp. 202–211. https://doi.org/10.1016/j.taap.2012.08.002

16. Brenner, M. and Hearling, V.G., The protective role of melanin against UV damage in human skin, Photochem. Photobiol., 2008, vol. 84, no. 3, pp. 539–549. https://doi.org/10.1111/j.1751-1097.2007.00226.x

17. Zeng-Yu, Y. and Jian-Hua, Q., Comparison of antioxidant activities of melanin fractions from chestnut shell, Molecules, 2016, vol. 21, p. 487. https://doi.org/10.3390/molecules21040487

18. Keypour, S., Riahi, H., Moradali, M., and Rafati, H., Investigation of the antibacterial activity of a chloroform extract of Ling Zhi or Reishi medicinal mushroom, Ganoderma lucidum (W. Curt.: Fr.) P. Karst. (Aphyllophoromycetideae), from Iran, Int. J. Med. Mushrooms, 2008, vol. 10, no. 4, pp. 345–349. https://doi.org/10.1615/IntJMedMushr.v10.i4.70

19. Racca, S., Spaccamiglio, A., Esculapio, P., Abba-dessa, G., Cangemi, L., DiCarlo, F., et al., Effects of swim stress and alpha-MSH acute pre-treatment on brain 5-HT transporter and corticosterone receptor, Pharmacol. Biochem. Behav., 2005, vol. 81, no. 4, pp. 894–900. https://doi.org/10.1016/j.pbb.2005.06.014

20. Chornenka, N.M., Raetska, Ya.B., Savchuk, O.M., Kompanets, I.V., Beregova, T.V., and Ostapchenko, L.I., Effect of different doses of melanin in the blood protein changes in rats under alkaline esophageal burns, Res. J. Pharm., Biol. Chem. Sci., 2017, vol. 8, no. 1, p. 261.

21. Seniuk, O., Gorovoj, L., and Kovalev, V., Anti-cancerogenic properties of melaninglucan complex from higher fungi, in Proc. 5th Int. Med. Mushroom Conf., Nantong, 2009, pp. 142–149. https://doi.org/10.1615/IntJMedMushr.v13.i1.20

22. Carletti, G., Nervo, G., and Cattivelli, L., Flavonoids and melanins: a common strategy across two kingdoms, Int. J. Biol. Sci., 2014, vol. 10, no. 10, pp. 1159–1170. https://doi.org/10.7150/ijbs.9672

23. Raetska, Ya.B., Ishchuk, T.V., Savchuk, O.M., and Ostapchenko, L.I., Experimental modeling of first-degree chemically-induced esophageal burns in rats, Med. Chem., 2013, vol. 15, no. 4, pp. 30–34.

24. Chyzhanska, N.V., Tsyryuk, O.I., and Beregova, T.V., The level of cortisol in the blood of rats before and after stress action against the background of melanin, Visn. Problem. Boil. Med., 2007, vol. 1, pp. 40–44.

25. Mishra, N.S., Wanjari, S.P., Parwani, R.N., Wanjari, P.V., and Kaothalker, S.P., Assessment of collagen and elastic fibres in various stages of oral submucous fibrosis using Masson’s trichrome, Verhoeff vangieson and picrosirius staining under light and polarizing microscopy, J. Dent. Spec., 2015, vol. 3, no. 2, pp. 170–175. https://doi.org/10.5958/2393-9834.2015.00009.1

26. Cerit, K.K., Halofuginone improves caustic-induced oxidative injury of esophagus in rats, Esophagus, 2018, vol. 15, no. 2, pp. 59–68. https://doi.org/10.1007/s10388-017-0594-4

27. Crowther, J.R., The ELISA Guidebook, Crowther: Humana Press, 2001. https://doi.org/10.1007/978-1-60327-254-4

28. Ozog, D.M., Liu, A., and Chaffins, M.L., Evaluation of clinical results, histological architecture, and collagen expression following treatment of mature burn scars with a fractional carbon dioxide laser, JAMA Dermatol., 2013, vol. 149, no. 1, pp. 50–57. https://doi.org/10.1001/2013

29. Tejiram, S., Zhang, J., Travis, T.E., et al., Compression therapy affects collagen type balance in hypertrophic scar, J. Surg. Res., 2016, vol. 201, no. 2, pp. 299–305. https://doi.org/10.1016/j.jss.2015.10.040

30. Ryu, H.H., Caustic injury: can CT grading system enable prediction of esophageal stricture?, Clin. Toxicol., 2010, vol. 48, no. 2, pp. 137–142. https://doi.org/10.3109/15563650903585929

31. Bozza, M.T., The role of MIF on eosinophil biology and eosinophilic inflammation, Clin. Rev. Aller. Immunol., 2019, pp. 1–10. https://doi.org/10.1007/s12016-019-08726-z

32. Muir, A.B., Wang, J.X., and Nakagawa, H., Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis, J. Gastroenterol., 2019, pp. 1–9. https://doi.org/10.1007/s00535-018-1498-3

33. Keane, T.J., Horejs, C.M., and Stevens, M.M., Scarring vs. functional healing: matrix-based strategies to regulate tissue repair, Adv. Drug Deliv. Rev., 2018, vol. 129, pp. 407–419. https://doi.org/10.1016/j.addr.2018.02.002

34. Komaki, Y., Hepatocyte growth factor facilitates esophageal mucosal repair and inhibits the submucosal fibrosis in a rat model of esophageal ulcer, Digestion, 2018, pp. 1–12. https://doi.org/10.1159/000491876

35. Belardelli, F., Role of interferons and other cytokines in the regulation of the immune response, APMIS, 1995, vol. 103, no. 3, pp. 161–179.

36. Zhou, J., Tu, J.J., and Huangetal, Y., Changes in serum contents of interleukin-6 and interleukin-10 and their relation with occurrence of sepsis and prognosis of severely burned patients, Zhonghua Shao Shang Za Zhi, 2012, vol. 28, no. 2, pp. 111–115.

37. Pileri, D., Palombo, A.A., D’Amelio, L., D’Arpa, N., Amato, G., Masellis, A., Cataldo, V., Mogavero, R., Napoli, B., Lombardo, C., and Conte, C., Concentrations of cytokines 2L-6 and 2L-10 in plasma of burn patients: their relationship to sepsis and outcome, Ann. Burns Fire Disasters, 2008, vol. 21, no. 4, pp. 182–185.

38. Chornenka, N.M., Raetska, Ya.B., Savchuk, O.M., Koval, T.V., Beregova, T.V., and Ostapchenko, L.I., Cytokine profile indicators in rat blood serum in a model of esophagus burn induced by antioxidant chemical preparation, Biomed. Res. Ther., 2017, vol. 4, no. 9, pp. 1591–1606. https://doi.org/10.15419/bmrat.v4i9.367

39. Kubo, H., Hayashi, T., Ago, K., Ago, M., Kanekura, T., and Ogata, M., Temporal expression of wound healing-related genes in skin burn injury, Leg. Med. (Tokyo), 2014, vol. 16, no. 1, pp. 8–13. https://doi.org/10.1016/j.legalmed.2013.10.002