Protective Effects of Tannic Acid–Loaded Selenium Nanoparticles against Peritoneal Adhesions via Regulating Oxidative Stress and Inflammatory Gene Expression

Document Type : Original Article

Authors

1 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Shahrekord, Shahrekord, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Shahrekord, Shahrekord, Iran

Abstract

Postoperative peritoneal adhesions remain a significant clinical challenge, often leading to serious complications such as chronic pain, intestinal obstruction, and infertility. Evidence indicates that oxidative stress and inflammation are key drivers of postoperative peritoneal adhesion formation. This study investigated the therapeutic potential of intraperitoneal administration of Tannic Acid (TA)-loaded selenium nanoparticles (SeNPs), in a rat model of surgically induced peritoneal adhesions. Thirty male Wistar rats (n=6 per group) were randomly divided into five groups to evaluate potential anti-adhesion therapies: sham (no adhesion induction), control (adhesion induction without treatment), SeNPs (1 mg/kg, single intraperitoneal (i.p.) dose after adhesion), tannic acid (TA, 20 mg/kg, single i.p. dose after adhesion), and a combination group (SeNPs + TA at the same doses, single i.p. dose after adhesion). All animals were killed 7 days later and cecum tissue samples were collected for biochemical and molecular analyses. Biochemical findings revealed a marked attenuation of oxidative stress, as evidenced by a significant decrease in xanthine oxidase activity and malondialdehyde levels in the SeNPs+TA group compared with the control group (p < 0.05). Gene expression analysis revealed a synergistic anti-inflammatory effect for the SeNPs+TA combination, which induced significantly greater downregulation of key pro-inflammatory mediators (particularly IL-1β and IL-6) compared to either monotherapy. At the level of upstream regulation, NF-κB expression followed a similar but non-significant decreasing trend, a finding that may reflect the limited duration of the single-dose treatment protocol. Collectively, these results suggest that tannic acid-loaded selenium nanoparticles exert potent antioxidant and anti-inflammatory actions, effectively targeting the principal molecular pathways involved in postoperative adhesion formation. Therefore, this combinatorial nanotherapeutic approach shows considerable promise as a therapeutic strategy for the management of postoperative peritoneal adhesions.

Keywords

Main Subjects

References

  1. Whang SH, Astudillo JA, Sporn E, Bachman SL, Miedema BW, Davis W, et al. In search of the best peritoneal adhesion model: comparison of different techniques in a rat model. J Surg Res. 2011;15;167(2):245-50
  2. Zhang H, Song Y, Li Z, Zhang T, Zeng L, Li W, et al. Evaluation of ligustrazine on the prevention of experimentally induced abdominal adhesions in rats. Int Surg J. 2015;1;21:115-21. https://doi.org/10.1016/j.ijsu.2015.06.081
  3. Kakanezhadi A, Rezaei M, Raisi A, Dezfoulian O, Davoodi F, Ahmadvand H. Rosmarinic acid prevents post-operative abdominal adhesions in a rat model. Sci Rep. 2022; 3;12(1):18593. https://doi.org/10.1038/s41598-022-22000-x
  4. Arung W, Meurisse M, Detry O. Pathophysiology and prevention of postoperative peritoneal adhesions. 2011;17(41):4545 https://doi.org/10.3748/wjg.v17.i41.4545
  5. Zhang ZL, Xu SW, Zhou XL. Preventive effects of chitosan on peritoneal adhesion in rats. World Journal of Gastroenterology: WJG. 2006; 28;12(28):4572. https://doi.org/10.3748/wjg.v12.i28.4572
  6. Lousse JC, Van Langendonckt A, González-Ramos R, Defrère S, Renkin E, Donnez J. Increased activation of nuclear factor-kappa B (NF-κB) in isolated peritoneal macrophages of patients with endometriosis. Fertil Steril. 2008;90(1):217-220. https://doi.org/10.1016/j.fertnstert.2007.06.015
  7. Awonuga AO, Belotte J, Abuanzeh S, Fletcher NM, Diamond MP, Saed GM. Advances in the pathogenesis of adhesion development: the role of oxidative stress. Reprod Sci. 2014;21(7):823-36. https://doi.org/10.1177/1933719114522550
  8. Khakzad MR. Effect of malva sylvestris extract on postoperative peritoneal adhesion in rats. Jundishapur J Nat 2019;2(3):211-216. https://doi.org/10.7508/nmj. 2015.03.006
  9. Mais V. Peritoneal adhesions after laparoscopic gastrointestinal surgery. World Journal of Gastroenterology. 2014;7;20(17):4917. https://doi.org/3748/wjg.v20.i17.4917
  10. Karthik KK, Cheriyan BV, Rajeshkumar S, Gopalakrishnan M. A review on selenium nanoparticles and their biomedical applications. Biomed Technol. 2024:1;6:61-74. https://doi.org/10.1016/j.bmt.2023.12.001
  11. Hosnedlova B, Kepinska M, Skalickova S, Fernandez C, Ruttkay-Nedecky B, Peng Q, et al. Nano-selenium and its nanomedicine applications: a critical review. Int J Nanomedicine. 2018:10:2107-28. https://doi.org/10.2147/IJN.S157541
  12. Xing H, Bai X, Pei X, Zhang Y, Zhang X, Chen S, et al. Synergistic anti-oxidative/anti-inflammatory treatment for acute lung injury with selenium based chlorogenic acid nanoparticles through modulating Mapk8ip1/MAPK and Itga2b/PI3k-AKT axis. J Nanobiotechnology. 2025;23;23(1):37. https://doi.org/10.1186/s12951-025-03114-6
  13. Sesia R, Ferraris S, Sangermano M, Spriano S. UV-cured chitosan-based hydrogels strengthened by tannic acid for the removal of copper ions from water. Polym. 2022; 1;14(21):4645. https://doi.org/10.3390/polym14214645
  14. Barboura M, Cornebise C, Hermetet F, Guerrache A, Selmi M, Salek A, et al. Tannic acid, a hydrolysable tannin, prevents transforming growth factor-β-induced epithelial–mesenchymal transition to counteract colorectal tumor growth. Cells. 2022; 17;11(22):3645. https://doi.org/10.3390/cells11223645
  15. Li Y, Liu G, Wang M, Zhang Y, You S, Zhang J, et al. The controlled release and prevention of abdominal adhesion of tannic acid and mitomycin C-loaded thermosensitive gel. 2023;16;15(4):975. https://doi.org/10.3390/polym15040975
  16. Shirian S, Emamjomehzadeh P, Javdani M, Khosravian P, Karimi B. Investigating the Therapeutic Effects of Selenium Nanoparticles and Tannic Acid on Postoperative Peritoneal Adhesion in Rats. J surg trauma. 2025;10;13(4):144-53. http://dx.doi.org/10.61882/jsurgtrauma.13.4.144
  17. Aiwale BS, Maurya R, Naqvi S. Green synthesized selenium nanoparticles mitigate cyclophosphamide-induced reproductive toxicity in male Wistar rats. Naunyn Schmiedebergs Arch Pharmacol. 2025;26:1-7. https://doi.org/10.21203/rs.3.rs-6759007/v1
  18. Zhou XW, Liao ZF, Liu LM. Effects of tannic acid pretreatment on cardiovascular function during hemorrhagic shock in rats. Zhongguo wei Zhong Bing ji jiu yi xue Chinese Critical Care Medicine Zhongguo Weizhongbing Jijiuyixue. 2009;1;21(7):425-8
  19. Mm B. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54. https://doi.org/10.1016/0003-2697(76)90527-3
  20. Peeri M, Haghigh MM, Azarbayjani MA, Atashak S, Behrouzi G. Effect of aqueous extract of saffron and aerobic training on hepatic non enzymatic antioxidant levels in streptozotocin-diabetic rats. Archives Des Sciences. 2012;65(10):525-32.
  21. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) Method. Methods. 2001;25:402–8. doi: 10.1006/meth.2001.1262. https://doi.org/10.1006/meth.2001.1262
  22. Chung HY, Baek BS, Song SH, Kim MS, Huh JI, Shim KH, Kim KW, Lee KH. Xanthine dehydrogenase/xanthine oxidase and oxidative stress. Age. 1997;20(3):127-40
  23. Zhang T, Ma C, Zhang Z, Zhang H, Hu H. NF‐κB signaling in inflammation and cancer. 2021;2(4):618-53. https://doi.org/10.1007/s11357-997-0012-2
  24. Zhang J, Wu Q, Song S, Wan Y, Zhang R, Tai M, et al. Effect of hydrogen-rich water on acute peritonitis of rat models. Int Immunopharmacol. 2014;21(1):94-101. https://doi.org/10.1016/j.intimp.2014.04.011
  25. Bahrami A, Khalaji A, Bahri Najafi M, Sadati S, Raisi A, Abolhassani A, et al. NF-κB pathway and angiogenesis: insights into colorectal cancer development and therapeutic targets. Eur J Med Res. 2024;19;29(1):610. https://doi.org/10.1186/s40001-024-02168-w
  26. Mal’tseva VN, Gudkov SV, Turovsky EA. Modulation of the functional state of mouse neutrophils by selenium nanoparticles in vivo. Int J Mol Sci. 2022;7;23(21):13651. https://doi.org/10.3390/ijms232113651
  27. Chen KM, Spratt TE, Stanley BA, De Cotiis DA, Bewley MC, Flanagan JM, et al. Inhibition of nuclear factor-κB DNA binding by organoselenocyanates through covalent modification of the p50 subunit. Cancer Res. 2007;67(21):10475-83. https://doi.org/10.1158/0008-5472.CAN-07-2510
  28. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2017;9(6):7204. https://doi.org/10.18632/oncotarget.23208
  29. Zaghloul RA, Abdelghany AM, Samra YA. Rutin and selenium nanoparticles protected against STZ-induced diabetic nephropathy in rats through downregulating Jak-2/Stat3 pathway and upregulating Nrf-2/HO-1 pathway. Eur J Pharmacol. 2022;15;933:175289. https://doi.org/10.1016/j.ejphar.2022.175289
  30. Ye L, Liu S, Zhang X, Wang C, Li P, Zhang C, et al. Dietary nano-selenium improves health of liver and intestine of grass carp Ctenopharyngodon idella after overwintering. A Anim Feed Sci. Technol. 2023;1;306:115817. https://doi.org/10.1016/j.anifeedsci.2023.115817
  31. Jing W, Xiaolan C, Yu C, Feng Q, Haifeng Y. Pharmacological effects and mechanisms of tannic acid. Biomed Pharmacother. 2022;154:113561. https://doi.org/10.1016/j.biopha.2022.113561
  32. Wu Y, Zhong L, Yu Z, Qi J. Anti‐neuroinflammatory effects of tannic acid against lipopolysaccharide‐induced BV2 microglial cells via inhibition of NF‐κB activation. Drug Dev Res. 2019;80(2):262-8. https://doi.org/10.1002/ddr.21490
  33. Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, et al. The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. Int J Mol Sci. 2021;8;22(5):2719. https://doi.org/10.3390/ijms22052719
  34. Alkhudhayri AA, Dkhil MA, Al-Quraishy S. Nanoselenium prevents eimeriosis-induced inflammation and regulates mucin gene expression in mice jejunum. Int J Nanomedicine. 2018;3:1993-2003. https://doi.org/10.2147/IJN.S162355
  35. Mi XJ, Le HM, Lee S, Park HR, Kim YJ. Silymarin-functionalized selenium nanoparticles prevent LPS-induced inflammatory response in RAW264. 7 cells through downregulation of the PI3K/Akt/NF-κB pathway. ACS omega. 2022;16;7(47):42723-32. https://doi.org/10.1021/acsomega.2c04140
  36. Zhang F, Li X, Wei Y. Selenium and selenoproteins in health. Biomolecules. 2023; 8;13(5):799. https://doi.org/10.3390/biom13050799
  37. Martínez-Esquivias F, Perez-Larios A, Guzmán-Flores JM. Effect of Administration of Selenium Nanoparticles Synthesized Using Onion Extract on Biochemical and Inflammatory Parameters in Mice Fed with High-Fructose Diet: In Vivo and In Silico Analysis. Biol Trace Elem Res. 2024;202(2):558-68. https://doi.org/10.1007/s12011-023-03685-1
  38. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;1;20(7):1126-67. https://doi.org/10.1089/ars.2012.5149
  39. Hong Y, Boiti A, Vallone D, Foulkes NS. Reactive oxygen species signaling and oxidative stress: transcriptional regulation and evolution. Antioxidants. 2024;1;13(3):312. https://doi.org/10.3390/antiox13030312
  40. Köse SA, Nazıroğlu M. Selenium reduces oxidative stress and calcium entry through TRPV1 channels in the neutrophils of patients with polycystic ovary syndrome. Biol Trace Elem Res. 2014;158(2):136-42. https://doi.org/10.1007/s12011-014-9929-3
  41. Ghaffari T, Nouri M, Saei AA, Rashidi MR. Aldehyde and xanthine oxidase activities in tissues of streptozotocin-induced diabetic rats: effects of vitamin E and selenium supplementation. Biol Trace Elem Res. 2012;147(1):217-25. https://doi.org/10.1007/s12011-011-9291-7
  42. Hatano T, YAsUHARA T, YosHIHARA R, AGATA I, NORO T, OkUDA T. Effects of interaction of tannins with co-existing substances. VII.: inhibitory effects of tannins and related polyphenols on xanthine oxidase. Chem Pharm Bull. 1990;25;38(5):1224-9. https://doi.org/10.1248/cpb.38.1224
Veterinary and Comparative Biomedical Research
Volume 3, Issue 2
June 2026
Pages 61-70

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