Features of Metabolism in Chronic Wound Remodelling

Keywords: Wound healing, Metabolism, Rats

Abstract


Background/Aim: The treatment of chronic wounds continues to be a pressing problem throughout the world. Healing occurs through some evolutionarily conserved biochemical pathways. The mechanisms of development of disorders of reparative regeneration are not fully understood. The work aimed to study the dynamics of changes in metabolic parameters during the healing of chronic wounds.

Methods: Healthy Wistar rats were divided into two groups. The animals of the first group were intact. Chronic wounds were simulated for the animals of the second group. On days 7, 14 and 28 after wound creation, the animals were euthanised. Biochemical parameters such as glucose, total protein, albumin, cholesterol, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were assessed in the blood serum of animals.

Results: It was found that the maximum decrease in glucose and total protein levels in the blood serum of animals in the experimental groups compared to intact animals was observed 2 weeks after surgery: the glucose concentration in rats was 1.7 times lower (p < 0.001). The level of albumin in the blood serum of experimental animals compared to intact animals was reduced by 1.5 times after 14 days (p < 0.001) and by 1.2 times after 28 days (p < 0.01). A week after surgery, the concentration of urea in the blood serum of experimental animals was 1.3 times higher (p < 0.01) than in intact rats and by day 28 after surgery, the urea level was 1.4 times higher (p < 0.001). The reduction in cholesterol and creatinine levels was not significant. An increase in AST, AST and ALP levels in the blood serum of experimental animals was shown. An increase in the blood serum of animals 7 days after surgery compared to the indicators of intact animals: ALP concentrations by 2.8 times (p < 0.001) and ALT concentrations by 1.4 times (p < 0.001) was established. The AST level significantly increased 14 days after surgery (p < 0.05).

Conclusions: The study of metabolic parameters allows monitoring of the state of the body during the healing process of wounds to correct treatment tactics.

Author Biographies

Sergey Pavlov, Kharkiv National Medical University

Department of Surgery No. 6

Nataliia Babenko, Kharkiv National Medical University

Department of Hygiene, Epidemiology, Disinfectology and Occupational Diseases

Marina Kumetchko, Kharkiv National Medical University

Department of Surgery No. 6

Olga Litvinova, Kharkiv National Medical University

Department of Surgery No. 6

Rostyslav Mikhaylusov, Kharkiv National Medical University

Department of Surgery No. 5

References

Zulkefli N, Che Zahari CNM, Sayuti NH, Kamarudin AA, Saad N, Hamezah HS, et al. Flavonoids as potential wound-healing molecules: emphasis on pathways perspective. Int J Mol Sci. 2023;24(5):4607. doi: 10.3390/ijms24054607.

Babenko NM, Litvinova OB, Pavlov SB, Kumechko MV, Komarchuk VV. Problems of healing chronic wounds. Mod Med Technol. 2023;3:66–70. doi: 10.34287/MMT.3(58).2023.10.

Pavlov SB, Tamm TI, Komisova TY, Babenko NM, Kumechko MV, Litvinova OB. The nature of changes in endocrine and immune factors at the initial stage of the formation of chronic wounds. Mod Med Technol. 2023;2:34–9. doi: 10.34287/MMT.2(57).2023.6.

Hunt M, Torres M, Bachar-Wikström E, Wikström JD. Multifaceted roles of mitochondria in wound healing and chronic wound pathogenesis. Front Cell Dev Biol. 2023;11:1252318. doi: 10.3389/fcell.2023.1252318.

Gupta S, Mujawdiya P, Maheshwari G, Sagar S. Dynamic role of oxygen in wound healing: a microbial, immunological, and biochemical perspective. Arch Razi Inst. 2022;77(2):513–23. doi: 10.22092/ARI.2022.357230.2003.

Protzman NM, Mao Y, Long D, Sivalenka R, Gosiewska A, Hariri RJ, et al. Placental-derived biomaterials and their application to wound healing: a review. Bioengineering (Basel). 2023;10(7):829. doi: 10.3390/bioengineering10070829.

Pavlov SB, Kumechko MV, Litvinova OB, Babenko NM, Goncharova AV. Bone regulatory mechanisms destruction in experimental chronic kidney disease. Fiziol Zh. 2016; 62(3):54–9. doi: 10.15407/fz62.03.054.

Pavlov SB, Babenko NM, Kumetchko MV, Litvinova OB, Semko NG, Mikhaylusov RN. The influence of photobiomodulation therapy on chronic wound healing. Rom Rep Phys. 2020;72:609.

Almadani YH, Vorstenbosch J, Davison PG, Murphy AM. Wound healing: a comprehensive review. Semin Plast Surg. 2021;35(3):141–4. doi: 10.1055/s-0041-1731791.

Pavlov SB, Litvinova OB, Babenko NM. Features of skin wound healing in rats with experimental chronic kidney disease. Regul Mech Biosyst. 2021;12(4):594–8. doi: 10.15421/022181.

Eming SA, Murray PJ, Pearce EJ. Metabolic orchestration of the wound healing response. Cell Metab. 2021;33(9):1726–43. doi: 10.1016/j.cmet.2021.07.017.

Wang Z, Zhao F, Xu C, Zhang Q, Ren H, Huang X, et al. Metabolic reprogramming in skin wound healing. Burns Trauma. 2024;12:tkad047. doi: 10.1093/burnst/tkad047.

Manchanda M, Torres M, Inuossa F, Bansal R, Kumar R, Hunt M, et al. metabolic reprogramming and reliance in human skin wound healing. J Invest Dermatol. 2023;143(10):2039-51.e10. doi: 10.1016/j.jid.2023.02.039.

Wang Q, Wang P, Qin Z, Yang X, Pan B, Nie F, et al. Altered glucose metabolism and cell function in keloid fibroblasts under hypoxia. Redox Biol. 2021;38:101815. doi: 10.1016/j.redox.2020.101815.

Valilshchykov M, Babalian V, Markina Т, Kumetchko M, Boiko L, Romaev S. The enalapril use in arterial hypertension stimulates the reparative processes in fractures of the proximal femur. Indones Biomed J. 2022;14(1):36–44. doi: 10.18585/inabj.v14i1.1736.

Neporozhnaya VM. Thrombocytes and some biochemical parameters of blood in patients with different results of healing of facial soft tissues. Bull Dentistry. 2022;118(1):39–42. doi: 10.35220/2078-8916-2022-43-1.7.

Handoo N, Parrah JD, Gayas MA, Athar H, Shah SA, Mir MS, et al. Effect of different extracts of R. emodi on hemato-biochemical parameters in rabbit wound healing model. J Pharmacogn Phytochem.2018;7(6):204–10.

de Albuquerque PBS, Rodrigues NER, Silva PMDS, de Oliveira WF, Correia MTDS, Coelho LCBB. The use of proteins, lipids, and carbohydrates in the management of wounds. Molecules. 2023;28(4):1580. doi: 10.3390/molecules28041580.

Lai WH, Rau CS, Wu SC, Chen YC, Kuo PJ, Hsu SY, et al. Post-traumatic acute kidney injury: a cross-sectional study of trauma patients. Scand J Trauma Resusc Emerg Med. 2016;24(1):136. doi: 10.1186/s13049-016-0330-4.

Inoue Y, Yu YM, Kurihara T, Vasilyev A, Ibrahim A, Oklu R, et al. Kidney and liver injuries after major burns in rats are prevented by resolvin D2. Crit Care Med. 2016;44(5):e241–52. doi: 10.1097/CCM.0000000000001397.

Haines RW, Zolfaghari P, Wan Y, Pearse RM, Puthucheary Z, Prowle JR. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019;45(12):1718–31. doi: 10.1007/s00134-019-05760-5.

Ischenko IO, Tynynyka LN, Kovaliev GA, Yefimova IA, Sandomirsky BP. Effect of cryopreserved cord blood serum on biochemical markers of destruction of tissues. J Exp Clin Med. 2016;1(70):19–25.

Krötzsch E, Salgado RM, Caba D, Lichtinger A, Padilla L, Di Silvio M. 162 alkaline phosphatase activity is related to acute inflammation and collagen turnover during acute and chronic wound healing. Wound Repair Regen. 2008;13. doi: 10.1111/j.1067-1927.2005.130216bn.x.

Al-Medhtiy MH, Jabbar AA, Shareef SH, Ibrahim IAA, Alzahrani AR, Abdulla MA. Histopathological evaluation of Annona muricata in TAA-induced liver injury in rats. Processes. 2022;10(8):1613. doi: 10.3390/pr10081613.

Han JH, Kwak JY, Lee SS, Kim HG, Jeon H, Cha RR. markedly elevated aspartate aminotransferase from non-hepatic causes. J Clin Med. 2022;12(1):310. doi: 10.3390/jcm12010310.

Vinaik R, Barayan D, Auger C, Abdullahi A, Jeschke MG. Regulation of glycolysis and the Warburg effect in wound healing. JCI Insight. 2020;5(17):e138949. doi: 10.1172/jci.insight.138949.

Wang X, Yu Z, Zhou S, Shen S, Chen W. The effect of a compound protein on wound healing and nutritional status. Evid Based Complement Alternat Med. 2022;2022:4231516. doi: 10.1155/2022/4231516.

Bogachkov YY, Chen L, Le Master E, Fancher IS, Zhao Y, Aguilar V, et al. LDL induces cholesterol loading and inhibits endothelial proliferation and angiogenesis in Matrigels: correlation with impaired angiogenesis during wound healing. Am J Physiol Cell Physiol. 2020;318(4):C762-C776. doi: 10.1152/ajpcell.00495.2018.

Matsuo K, Matsuzaki S, Roman LD, Klar M, Wright JD. Proposal of an endometrial cancer staging schema with stage-specific incorporation of malignant peritoneal cytology. Am J Obstet Gynecol. 2021 Mar;224(3):319-21. doi: 10.1016/j.ajog.2020.10.045.

Kierans AS, Bennett GL, Haghighi M, Rosenkrantz AB. Utility of conventional and diffusion-weighted MRI features in distinguishing benign from malignant endometrial lesions. Eur J Radiol. 2014 Apr;83(4):726-32. doi: 10.1016/j.ejrad.2013.11.030.

Mansour TMM, Ahmed YAA-a, Ahmed GAE-R. The usefulness of diffusion-weighted MRI in the differentiation between focal uterine endometrial soft tissue lesions. Egypt J Radiol Nucl Med. 2019;50(1):102. doi: 10.1186/s43055-019-0076-x.

Fujii S, Matsusue E, Kigawa J, Sato S, Kanasaki Y, Nakanishi J, et al. Diagnostic accuracy of the apparent diffusion coefficient in differentiating benign from malignant uterine endometrial cavity lesions: initial results. Eur Radiol. 2008 Feb;18(2):384-9. doi: 10.1007/s00330-007-0769-9.

Ahmed SA, El Taieb HA, Abotaleb H. Diagnostic performance of sonohysterography and MRI diffusion in benign endometrial lesion characterization. Egypt J Radiol Nucl Med. 2018;49(2):579–89. doi: 10.1016/j.ejrnm.2018.02.010.

Gharibvand MM, Ahmadzadeh A, Asadi F, Fazelinejad Z. The diagnostic precision of apparent diffusion coefficient (ADC) in grading of malignant endometrial lesions compared with histopathological findings. J Family Med Prim Care. 2019;8(10):3372–8. doi: 10.4103/jfmpc.jfmpc_142_19.

Masroor I, Zeeshan M, Afzal S, Ahmad N, Shafqat G. Diffusion weighted MR imaging (DWI) and ADC values in endometrial carcinoma. J Coll Physicians Surg Pak. 2010 Nov;20(11):709-13. PMID: 21078241.

Latif MA, Tantawy MS, Mosaad HS. Diagnostic value of diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) in differentiation between normal and abnormally thickened endometrium: prospective study. Egypt J Radiol Nucl Med. 2021;52:107. doi: 10.1186/s43055-021-00487-0.

Kececi IS, Nural MS, Aslan K, Danacı M, Kefeli M, Tosun M. Efficacy of diffusion-weighted magnetic resonance imaging in the diagnosis and staging of endometrial tumors. Diagn Interv Imaging. 2016 Feb;97(2):177-86. doi: 10.1016/j.diii.2015.06.013.

Beddy P, Moyle P, Kataoka M, Yamamoto AK, Joubert I, Lomas D, et al. Evaluation of depth of myometrial invasion and overall staging in endometrial cancer: comparison of diffusion-weighted and dynamic contrast-enhanced MR imaging. Radiology. 2012 Feb;262(2):530-7. doi: 10.1148/radiol.11110984.

Nougaret S, Reinhold C, Alsharif SS, Addley H, Arceneau J, Molinari N, et al. Endometrial cancer: combined MR volumetry and diffusion-weighted imaging for assessment of myometrial and lymphovascular invasion and tumor grade. Radiology. 2015 Sep;276(3):797-808. doi: 10.1148/radiol.15141212.

Rechichi G, Galimberti S, Signorelli M, Perego P, Valsecchi MG, Sironi S. Myometrial invasion in endometrial cancer: diagnostic performance of diffusion-weighted MR imaging at 1.5-T. Eur Radiol. 2010 Mar;20(3):754-62. doi: 10.1007/s00330-009-1597-x.

Gil RT, Cunha TM, Horta M, Alves I. The added value of diffusion-weighted imaging in the preoperative assessment of endometrial cancer. Radiol Bras. 2019 Jul-Aug;52(4):229-36. doi: 10.1590/0100-3984.2018.0054.

Published
2024/02/23
Section
Original article