Features of skin wound healing in rats with experimental chronic kidney disease

  • S. B. Pavlov Kharkiv Medical Academy of Postgraduate Education
  • O. B. Litvinova H. S. Skovoroda Kharkiv National Pedagogical University
  • N. M. Babenko Kharkiv Medical Academy of Postgraduate Education
DOI: https://doi.org/10.15421/022181
Keywords: renal pathology; skin regeneration; chronic wounds; interleukins; basic fibroblast growth factor; vascular endothelial growth factor.

Abstract

Chronic kidney disease negatively affects the morphofunctional state of all organs due to hemodynamic and metabolic disorders. Changes in the content of cytokines observed in kidney diseases, which regulate the processes of inflammation and tissue repair, can complicate the course of the wound process. This research aimed to study disorders in the process of skin wound repair due to changes in the dynamics of production of interleukins IL-1β, IL-6, IL-10, IL-4, growth factors bFGF and VEGF in animals with experimental chronic kidney disease. The levels of interleukins and growth factors were determined on the 7th, 14th and 28th days after surgical modeling of wounds in the blood of rats with experimental chronic kidney disease and animals of the control group. To assess the dynamics and quality of wound healing, a semi-quantitative histological analysis was performed. The study showed an increase in the content of pro-inflammatory interleukins in the group of sick rats: on the 7th day the level of IL-1β was 1.19 times higher, and IL-6 – 1.55 times, on the 14th day the level of IL-1β was 1.37 times in comparison with the control group. The maximum increase in the concentration of anti-inflammatory interleukins was noted on the 28th day: IL-4 was 2.10 times higher, IL-10 – 1.39 times higher than in the control group. The content of bFGF and VEGF in animals of the control group reached its maximum on the 7th day, and in animals with chronic kidney disease – on the 15th day after surgery. Semi-quantitative histological analysis showed a decrease in indicators in the group of sick animals: the number of fibroblasts and collagen deposition – on the 7th day, reepithelialization – on the 28th day. A persistent increase in the number of polymorphonuclear leukocytes was also noted at all periods of the experiment: by 1.38, 1.99, and 9.82 times – on the 7th, 14th, and 28th days, respectively. The study showed that the dynamics of the production of interleukins and growth factors were impaired in rats with chronic kidney disease. In the process of damage regeneration in sick animals, pro-inflammatory mechanisms prevailed with the involvement of a large number of immunocompetent cells, as a result, skin wounds took longer to heal.

References

Ammirati, A. L. (2020). Chronic kidney disease. Revista da Associação Médica Brasileira, 66, 3–9.

Anders, H.-J. (2016). Of inflammasomes and alarmins: IL-1β and IL-1α in kidney disease. Journal of the American Society of Nephrology, 27(9), 2564–2575.

Barreto, D. V., Barreto, F. C., Liabeuf, S., Temmar, M., Lemke, H.-D., Tribouilloy, C., Choukroun, G., Vanholder, R., & Massy, Z. A. (2010). Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease. Kidney International, 77(6), 550–556.

Beyene, R. T., Derryberry, J. S. L., & Barbul, A. (2020). The effect of comorbidities on wound healing. The Surgical clinics of North America, 100(4), 695–705.

Bodnár, E., Bakondi, E., Kovács, K., Hegedűs, C., Lakatos, P., Robaszkiewicz, A., Regdon, Z., Virág, L., & Szabó, É. (2018). Redox profiling reveals clear differences between molecular patterns of wound fluids from acute and chronic wounds. Oxidative Medicine and Cellular Longevity, 2018, 5286785.

Chao, C.-C., Wu, V.-C., Tan, C.-H., Wang, Y.-M., Tseng, M.-T., Wu, P.-C., Lin, Y.-H., Lin, W.-M., Wu, K.-D., & Hsieh, S.-T. (2011). Skin denervation and its clinical significance in late-stage chronic kidney disease. Archives of Neurology, 68(2), 200–206.

Dissemond, J. (2017). Chronic leg ulcers. Der Hautarzt, 68(8), 614–620.

Gal, P., Kilik, R., Mokry, M., Vidinsky, B., Vasilenko, T., Mozes, S., Bobrov, N., Tomori, Z., & Bober, J. (2008). Simple method of open skin wound healing model in corticosteroid-treated and diabetic rats: standardization of semi-quantitative and quantitative histological assessments. Veterinární Medicína, 12, 652–659.

Gupta, J., Mitra, N., Kanetsky, P. A, Devaney, J., Wing, M. R., Reilly, M., Shah, V. O., Balakrishnan, V. S., Guzman, N. J., Girndt, M., Periera, B. G., Feldman, H. I., Kusek, J. W., Joffe, M. M., & Raj, D. S. (2012). Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clinical Journal of the American Society of Nephrology, 7(12), 1938–1946.

Hirano, T. (2021). IL-6 in inflammation, autoimmunity and cancer. International Immunology, 33(3), 127–148.

Honnegowda, T. M., Kumar, P., Udupa, E. G. P., Kumar, S., Kumar, U., & Rao, P. (2015). Role of angiogenesis and angiogenic factors in acute and chronic wound healing. Plastic and Aesthetic Research, 2, 243–249.

Li, F., Wang, M., Wang, J., Li, R. & Zhang, Y. (2019). Alterations to the gut microbiota and their correlation with inflammatory factors in chronic kidney disease. Frontiers in Cellular and Infection Microbiology, 9, 206.

Kang, D. H., Joly, A. H., Oh, S. W., Hugo, C., Kerjaschki, D., Gordon, K. L., Mazzali, M., Jefferson, J. A., Hughes, J., Madsen, K. M., Schreiner, G. F., & Johnson, R. J. (2001). Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. Journal of the American Society of Nephrology, 12, 1434–1447.

Kondakov, I. I., Topchii, I. I., & Kirienko, O. M. (2013). Influence of glicerol on functional-morphological indicators of kidneys at modelling renal insufficiency in rats. Ukrainian Journal of Nephrology and Dialysis, 39, 14–20.

Krzystek-Korpacka, M., Kędzior, K., Masłowski, L., Mierzchała, M., Bednarz-Misa, I., Bronowicka-Szydełko, A., Kubiak, J., Gacka, M., Płaczkowska, S., & Gamian, A. (2019). Impact of chronic wounds of various etiology on systemic profiles of key inflammatory cytokines, chemokines and growth factors, and their interplay. Advances in Clinical and Experimental Medicine, 28(10), 1301–1309.

Maroz, N., & Simman, R. (2014). Wound healing in patients with impaired kidney function. The Journal of the American College of Clinical Wound Specialists, 5(1), 2–7.

Narazaki, M., & Kishimoto, T. (2018). The two-faced cytokine Il-6 in host defense and diseases. International Journal of Molecular Sciences, 19(11), 3528.

Pavlov, S., Kumetchko, M., Litvinova, O., Babenko, N., Valilshchykov, N., & Shamas, O. (2019). Features of morphological changes in the skin during wound healing. Journal of Morphological Sciences, 2(2), 22–30.

Pavlov, S., Babenko, N., Kumetchko, M., Litvinova, O., Semko, N., & Pavlova, O. (2019). Intercellular mediators in bone remodeling regulation in the experimental renal pathology. Actualizaciones en Osteología, 15(3), 180–190.

Petreski, T., Piko, N., Ekart, R., Hojs, R., & Bevc, S. (2021). Review on inflammation markers in chronic kidney disease. Biomedicines, 9(2), 182.

Robles-Mendez, J. C., Vazquez-Martinez, O., & Ocampo-Candiani, J. (2015). Skin manifestations of chronic kidney disease. Actas Dermo-Sifiliográficas, 106(8), 609–622.

Romanova, Y., Laikov, A., Markelova, M., Khadiullina, R., Makseev, A., Hasanova, M., Rizvanov, A., Khaiboullina, S., & Salafutdinov, I. (2020). Proteomic analysis of human serum from patients with chronic kidney disease. Biomolecules, 10(2), 257.

Querfeld, U., Mak, R. H., & Pries, A. R. (2020). Microvascular disease in chronic kidney disease: The base of the iceberg in cardiovascular comorbidity. Clinical science, 134(12), 1333–1356.

Seth, A. K., De la Garza, M., Fang, R. C, Hong, S. J., & Galiano, R. D. (2013). Excisional wound healing is delayed in a murine model of chronic kidney disease. PloS One, 8(3), e59979.

Sheng, W.-S., Xu, H.-L., Zheng, L., Zhuang, Y.-D., Jiao, L.-Z., Zhou, J.-F., ZhuGe, D.-L., Chi, T.-T., Zhao, Y.-Z., & Lan, L. (2018). Intrarenal delivery of bFGF-loaded liposome under guiding of ultrasound-targeted microbubble destruction prevent diabetic nephropathy through inhibition of inflammation. Artificial Cells, Nanomedicine, and Biotechnology, 46(2), 373–385.

Souza, M. K., Neves, R. V. P., Rosa, T. S., Cenedeze, M. A., Arias, S. C. A., Fujihara, C. K., Bacurau, R. F. P., Câmara, N. O. S., Moraes, M. R., & Filho, A. P. E. S. (2018). Resistance training attenuates inflammation and the progression of renal fibrosis in chronic renal disease. Life Sciences, 206, 93–97.

Summers, S. A., Phoon, R. K., Odobasic, D., Dewage, L., Kitching, A. R., & Holdsworth, S. R. (2011). Signal transducer and activation of transcription 6 (STAT6) regulates T helper type 1 (Th1) and Th17 nephritogenic immunity in experimental crescentic glomerulonephritis. Clinical and Experimental Immunology, 166, 227–234.

Steen-Louws, C., Hartgring, S. A. Y., Popov-Celeketic, J., Lopes, A. P., de Smet, M. B. M., Eijkelkamp, N., Lafeber, F. P. J. G., Hack, C. E., & van Roon, J. A. G. (2019). IL4-10 fusion protein: A novel immunoregulatory drug combining activities of interleukin-4 and interleukin-10. Clinical and Experimental Immunology, 195(1), 1–9.

Stompór, T., Zdzienicka, A., Motyka, M., Dembińska-Kieć, A., Davies, S. J., & Sulowicz, W. (2002). Selected growth factors in peritoneal dialysis: Their relationship to markers of inflammation, dialysis adequacy, residual renal function, and peritoneal membrane transport. Peritoneal Dialysis International, 22(6), 670–676.

Tanaka, S., Tanaka, T., & Nangaku, M. (2015). Hypoxia and dysregulated angiogenesis in kidney disease. Kidney Diseases, 1, 80–89.

Vanholder, R., Annemans, L., Brown, E., Gansevoort, R., Gout-Zwart, J. J., Lameire, N., Morton, R. L., Oberbauer, R., Postma, M. J., Tonelli, M., Van Biesen, W., & Zoccali, C. (2017). Reducing the costs of chronic kidney disease while delivering quality health care: A call to action. Nature Reviews, Nephrology, 13, 393–409.

Vlahovic, P., Cvetkovic, T., Savic, V., & Stefanovic, V. (2007). Dietary curcumin does not protect kidney in glycerol-induced acute renal failure. Food and Chemical Toxicology, 45(9), 1777–1782.

Wang, C., Wang, M., Xu, T., Zhang, X., Lin, C., Gao, W., Xu, H., Lei, B., & Mao, C. (2019). Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics, 9(1), 65–76.

Zhu, Z. X., Sun, C. C., Ting, Z. Y., Wang, Y., Wang, T., Chi, L. S., Cai, W. H., Zheng, J. Y., Zhou, X., Cong, W. T., Li, X. K., & Jin, L. T. (2017). Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration. Experimental Cell Research, 355(2), 83–94.

Zinatullin, R. M., Gizatullin, T. R., Pavlov, V. N., Kataev, V. A., Farhutdinov, R. R., & Baymurzina, J. L. (2014). A method for modeling a trophic wound in an experiment. Russian Patent RF 2510083.

Published
2021-10-03
How to Cite
Pavlov, S. B., Litvinova, O. B., & Babenko, N. M. (2021). Features of skin wound healing in rats with experimental chronic kidney disease . Regulatory Mechanisms in Biosystems, 12(4), 594-598. https://doi.org/10.15421/022181
Issue
Vol 12 No 4 (2021): Regulatory Mechanisms in Biosystems
Section
Статті
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.