Paediatric Surgery (Ukraine).2023.1(78): 72-78; doi 10.15574/PS.2023.78.72
F.T. Akhmedov¹, H.B. Isayev², S.V. Guliyeva^3
1Main Clinical Hospital of the Armed Forces of the Ministry of Defence of the Republic of Azerbaijan, Baku
²M.A. Topchubashov Scientific and Surgical Center, Baku, Azerbaijan
³Azerbaijan Medical University, Baku

For citation: Akhmedov FT, Isayev HB, Guliyeva SV. (2023). Effect of anti-adhesion agents on cytokine profile in an experimental model of postoperative intra-abdominal adhesions. Paediatric Surgery (Ukraine). 1(78): 72-78; doi 10.15574/PS.2023.78.72.
Article received: Nov 12, 2022. Accepted for publication: Mar 14, 2023.

Many attempts have been made to prevent peritoneal adhesions using anti-adhesion agents, barriers and other therapeutic approaches, but their efficacy has not been widely accepted.
Purpose – to determine the effects of mezogel, a mixture of metronidazole, dextran, and contrykal enriched with oxygen based on the pro- and anti-inflammatory cytokine concentration in rats with simulated postoperative peritoneal adhesions.
Materials and methods. A total of 90 outbred white rats, divided into three groups of 30 animals each, underwent laparotomy and mechanical injury of the small bowel wall until a drop of blood appeared. After mechanical injury of the small bowel wall, the abdominal wound in group 1 animals (control) was closed with a layered suture technique; group 2 animals (comparison) were administered one mL of mezogel into the abdominal cavity before layer-by-layer suturing; group 3 animals (experimental) were introduced one mL of a specially prepared mixture of metronidazole, dextran, and contrykal (in a ratio of 1:1:0.1, respectively) enriched with oxygen into the abdominal cavity before the laparotomy wound was closed. Each surgical intervention lasted 15–20 minutes. On days 5, 10 and 21 of the experiment interleukin (IL) 4, IL-6, IL-10 and tumour necrosis factor alpha (TNF-α) were determined in the blood by enzyme immunoassay using corresponding test kits manufactured by Bender Medsystems (Austria).
Results. The levels of the anti-inflammatory cytokines IL-4 and IL-10 increased dynamically in groups 2 and 3, while group 1 showed their decrease. The proinflammatory cytokine IL-6 and TNF-α concentration decreased in the experimental and comparison groups during the study period. On day 5 in groups 2 and 3, compared to group 1, the IL-6 concentration was reduced by 28.4% (p=0.029) and 41.0% (p=0.006), respectively. Group 3 animals had a 17.6% (p=0.043) lower IL-6 level compared to group 2 animals. On days 10 and 21 a dynamic decrease in IL-6 was observed in the animals of groups 2 and 3. Group 3 animals had the lowest TNF-α, 41.9 % (p=0.001) lower than in group 1, and 31.7 % (p=0.118) lower than in group 2. There were significant strong relationships detected between IL-10 and IL-6 in all groups on day 5 of the study.
Conclusions. The administration of anti-adhesion agents, mezogel and an oxygen-enriched mixture of metronidazole, dextran, and contrykal, inhibits inflammation, which is expressed as a decrease in the concentrations of IL-6 and TNF-α. These agents lead to a negative interaction of anti-inflammatory cytokines with pro-inflammatory cytokines, in particular IL-4 with IL-6 and IL-10 with IL-6, indicating a greater prophylactic effect.
The experiments with laboratory animals were provided in accordance with all bioethical norms and guidelines.
No conflict of interests was declared by the authors.
Keywords: postoperative intra-abdominal adhesions, mezogel, metronidazole, dextran, contrykal, cytokines, correlation.

REFERENCES

1. Akhmedov FT. (2022). Types and Localization of Abdominal Adhesions after Open Operations (Experimental Study). Paediatric Surgery (Ukraine). 4(77): 34-39. doi: 10.15574/PS.2022.77.34.

2. Ambler DR, Fletcher NM, Diamond MP, Saed GM. (2012). Effects of hypoxia on the expression of inflammatory markers IL-6 and TNF-a in human normal peritoneal and adhesion fibroblasts. Systems biology in reproductive medicine. 58: 324-329. https://doi.org/10.3109/19396368.2012.713439; PMid:23043632

3. Biondo-Simões MLP, Oda MH, Pasqual S, Robes RR. (2018). Comparative study of polyglactin 910 and simple catgut in the formation of intraperitoneal adhesions. Acta Cirurg. Bras. 33: 102-109. https://doi.org/10.1590/s0102-865020180020000001; PMid:29513808

4. Cai J, Guo J, Wang S. (2023). Application of Polymer Hydrogels in the Prevention of Postoperative Adhesion: A Review. Gels. 9 (2): 98. https://doi.org/10.3390/gels9020098; PMid:36826268 PMCid:PMC9957106

5. Capella-Monsonís H, Kearns S, Kelly J, Zeugolis DI. (2019). Battling adhesions: from understanding to prevention. BMC Biomed Eng. 1: 5. https://doi.org/10.1186/s42490-019-0005-0; PMid:32903353 PMCid:PMC7412649

6. Ding H, Li H, Yu H, Zhang W, Li S. (2020). Cytokines in abdominal exudate and serum predict small bowel obstruction following appendectomy. ANZ Journal of Surgery. 90 (10): 1991-1996. https://doi.org/10.1111/ans.16241; PMid:32808444

7. Ersoy E, Ozturk V, Yazgan A, Ozdogan M, Gundogdu H. (2009). Comparison of the two types of bioresorbable barriers to prevent intra-abdominal adhesions in rats. J Gastrointest Surg. 13 (2): 282-286. https://doi.org/10.1007/s11605-008-0678-5; PMid:18777122

8. Hassanabad AF, Zarzycki AN, Jeon K, Dundas JA, Vasanthan V, Deniset JF et al. (2021). Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies. Biomolecules. 11 (7): 1027. https://doi.org/10.3390/biom11071027; PMid:34356652 PMCid:PMC8301806

9. Lin L-X, Yuan F, Zhang H-H, Liao N-N, Luo J-W, Sun Y-L. (2017). Evaluation of surgical anti-adhesion products to reduce postsurgical intra-abdominal adhesion formation in a rat model. PLoS ONE. 12 (2): e0172088. https://doi.org/10.1371/journal.pone.0172088; PMid:28207824 PMCid:PMC5312873

10. Liu M, Li P. (2012). Clinical value of anti-adhesion agents used in laparotomy in obstetrics and gynecology. Chin J Obstet Gynecol. 47 (4): 255-258.

11. Ma F, Shi M. (2012). Clinical observation of adhesion inhibition with application of DL-polylactic acid medical film to abdominal surgeries. China Med Eng. 20 (4): 68-69.

12. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. (2011). Guide for the Care and Use of Laboratory Animals. 8th edition. Washington (DC): National Academies Press (US); The National Academies Collection: Reports funded by National Institutes of Health: 246.

13. Rocha J, Eduardo-Figueira M, Barateiro A, Fernandes A, Brites D, Bronze R et al. (2015). Anti-inflammatory effect of rosmarinic acid and an extract of Rosmarinus officinalis in rat models of local and systemic inflammation. Basic Clin Pharmacol Toxicol. 116 (5): 398-413. https://doi.org/10.1111/bcpt.12335; PMid:25287116

14. Tang J, Xiang Z, Bernards MT, Chen S. (2020). Peritoneal adhesions: Occurrence, prevention and experimental models. Acta Biomater. 116: 84-104. https://doi.org/10.1016/j.actbio.2020.08.036; PMid:32871282

15. Torres K, Pietrzyk Ł, Plewa Z, Załuska-Patel K, Majewski M, Radzikowska E et al. (2018). TGF-β and inflammatory blood markers in prediction of intraperitoneal adhesions. Adv Med Sci. 63 (2): 220-223. https://doi.org/10.1016/j.advms.2017.11.006; PMid:29223125

16. Tsai JM, Sinha R, Seita J, Fernhoff N, Christ S, Koopmans T et al. (2018). Surgical adhesions in mice are derived from mesothelial cells and can be targeted by antibodies against mesothelial markers. Sci Transl Med. 10 (469): eaan6735. https://doi.org/10.1126/scitranslmed.aan6735; PMid:30487249

17. Uyama N, Tsutsui H, Wu S, Yasuda K, Hatano E, Qin X-Y et al. (2019). Anti-interleukin-6 receptor antibody treatment ameliorates postoperative adhesion formation. Sci Rep. 9: 17558. https://doi.org/10.1038/s41598-019-54175-1; PMid:31772282 PMCid:PMC6879753

18. Ward BC, Panitch A. (2011). Abdominal adhesions: current and novel therapies. J Surg Res. 165 (1): 91-111. https://doi.org/10.1016/j.jss.2009.09.015; PMid:20036389

19. Wei G, Wu Y, Gao Q, Zhou C, Wang K, Shen C et al. (2017). Effect of Emodin on Preventing Postoperative Intra-Abdominal Adhesion Formation. Oxid Med Cell Longev: 740317. https://doi.org/10.1155/2017/1740317; PMid:28831292 PMCid:PMC5558648