The Effect of Silver Water (Ag) Administration on NF-κB Expression and Histopathology of Gastric in Rats Model of Inflammatory Bowel Disease

Authors

DOI:

https://doi.org/10.5380/avs.v30i4.99059

Keywords:

Anti-inflammatory, Antioxidant, IBD, Indomethacin, Silver Water, Pathology

Abstract

Abstract: This study investigated the therapeutic effects of silver water on indomethacin-induced Inflammatory Bowel Disease (IBD) in rats. Male white rats (12 weeks old, ~250g) were divided into five groups: negative control (untreated), positive control (indomethacin-induced), and three treatment groups (T1, T2, T3) receiving 1, 2, and 3 ml of 25 ppm silver water, respectively for 14 days following indomethacin induction (15 mg/kg BW). The study evaluated NF-κB expression via immunohistochemistry and gastric histopathological changes using hematoxylin-eosin staining. Data were analyzed using ANOVA followed by the Tukey test (α = 0.05). Results demonstrated that silver water therapy at all tested volumes significantly reduced NF-κB expression, inflammatory cell infiltration, and epithelial erosion in gastric tissues compared to the positive control. The 3 ml dose showed the most pronounced therapeutic effect. These findings suggest that silver water possesses anti-inflammatory properties that suppress the NF-κB inflammatory pathway and promote gastric tissue repair in indomethacin-induced IBD, potentially offering a novel therapeutic approach for IBD management.

Author Biographies

Cindy Ercha Aulia Putri, Universitas Lambung Mangkurat

Departement of Veterinary Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Banjarmasin, Indonesia

Aldin Akbar Rahmatullah, Universitas Lambung Mangkurat

Departement of Veterinary Medicine, Faculty of Medicine and Health Sciences, Universitas Lambung Mangkurat, Banjarmasin, Indonesia and Veterinarian, AAR Vet Clinic, Banjarbaru, Indonesia 

Anna Roosdiana, Universitas Brawijaya

Departement of Veterinary Medicine, Faculty of Veterinary Medicine, Universitas Brawijaya, Malang, Indonesia

Yudit Oktanella, Universitas Brawijaya

Departement of Veterinary Medicine, Faculty of Veterinary Medicine, Universitas Brawijaya, Malang, Indonesia

References

Abdellatif, K. R., Abdelall, E. K., Elshemy, H. A., El‐Nahass, E. S., Abdel‐Fattah, M. M., and Abdelgawad, Y. Y. (2021). New indomethacin analogs as selective COX‐2 inhibitors: Synthesis, COX‐1/2 inhibitory activity, anti‐inflammatory, ulcerogenicity, histopathological, and docking studies. Archiv der Pharmazie, 354(4), 2000328. https://doi.org/10.1002/ardp.202000328

Ananthakrishnan, A. N., and Xavier, R. J. (2020). Gastrointestinal diseases. In Hunter's Tropical Medicine and Emerging Infectious Diseases (pp. 16-26). Elsevier. https://doi.org/10.1016/B978-0-323-55512-8.00003-X

Andrade, B., Jara-Gutiérrez, C., Paz-Araos, M., Vázquez, M. C., Díaz, P., and Murgas, P. (2022). The relationship between reactive oxygen species and the cGAS/STING signaling pathway in the inflammaging process. International journal of molecular sciences, 23(23), 15182. https://doi.org/10.3390/ijms232315182

Bastaki, S. M., Al Ahmed, M. M., Al Zaabi, A., Amir, N., and Adeghate, E. (2016). Effect of turmeric on colon histology, body weight, ulcer, IL-23, MPO, and glutathione in acetic-acid-induced inflammatory bowel disease in rats. BMC complementary and alternative medicine, 16, 1-14. https://doi.org/10.1186/s12906-016-1057-5

Bhatt, D., and Ghosh, S. (2014). Regulation of the NF-κB-mediated transcription of inflammatory genes. Frontiers in immunology, 5, 71. https://doi.org/10.3389/fimmu.2014.00071

Bi, Y., Marcus, A. K., Robert, H., Krajmalnik-Brown, R., Rittmann, B. E., Westerhoff, P., and Mercier-Bonin, M. (2020). The complex puzzle of dietary silver nanoparticles, mucus, and microbiota in the gut. Journal of Toxicology and Environmental Health, Part B, 23(2), 69-89. https://doi.org/10.1080/10937404.2019.1710914

Burdușel, A. C., Gherasim, O., Grumezescu, A. M., Mogoantă, L., Ficai, A., and Andronescu, E. (2018). Biomedical applications of silver nanoparticles: an up-to-date overview. Nanomaterials, 8(9), 681. https://doi.org/10.3390/nano8090681

Bures, J., Pejchal, J., Kvetina, J., Tichý, A., Rejchrt, S., Kunes, M., and Kopacova, M. (2011). Morphometric analysis of the porcine gastrointestinal tract in a 10-day high-dose indomethacin administration with or without probiotic bacteria Escherichia coli Nissle 1917. Human & Experimental Toxicology, 30(12), 1955-1962. https://doi.org/10.1177/0960327111403174

Cao, S. G., Chen, R., Wang, H., Lin, L. M., and Xia, X. P. (2018). Cryptotanshinone inhibits prostaglandin E2 production and COX-2 expression via suppression of TLR4/NF-κB signaling pathway in LPS-stimulated Caco-2 cells. Microbial pathogenesis, 116, 313-317. https://doi.org/10.1016/j.micpath.2017.12.027

Chandan, V. S. (2019). Normal histology of gastrointestinal tract. Surgical Pathology of Non-neoplastic Gastrointestinal Diseases, 3-18.. https://doi.org/10.1007/978-3-030-15573-5_1

Chaudhary, P., Janmeda, P., Docea, A. O., Yeskaliyeva, B., Abdull Razis, A. F., Modu, B., Calina, D., and Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: Potential crosstalk in the pathophysiology of human diseases. Frontiers in chemistry, 11, 1158198. https://doi.org/10.3389/fchem.2023.1158198

Cheng, H., Huang, H., Guo, Z., Chang, Y., and Li, Z. (2021). Role of prostaglandin E2 in tissue repair and regeneration. Theranostics, 11(18), 8836. https://doi.org/10.7150%2Fthno.63396

Craven, M., Simpson, J. W., Ridyard, A. E., and Chandler, M. L. (2004). Canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases (1995–2002). Journal of Small Animal Practice, 45(7), 336-342. https://doi.org/10.1111/j.1748-5827.2004.tb00245.x

Crosby, K., Simendinger, J., Grange, C., Ferrante, M., Bernier, T., and Stanen, C. (2016). Immunohistochemistry protocol for paraffin-embedded tissue section-advertisement. Cell Signal. Technol, 10, 5064.

Dang, S. C., Wang, H., Zhang, J. X., Cui, L., Jiang, D. L., Chen, R. F., Qu, J. G., Shen, X. Q., Chen, M., and Gu, M. (2015). Are gastric mucosal macrophages responsible for gastric injury in acute pancreatitis?. World Journal of Gastroenterology: WJG, 21(9), 2651. https://doi.org/10.3748%2Fwjg.v21.i9.2651

Delgado-Rizo, V., Martínez-Guzmán, M. A., Iñiguez-Gutierrez, L., García-Orozco, A., Alvarado-Navarro, A., and Fafutis-Morris, M. (2017). Neutrophil extracellular traps and their implications in inflammation: an overview. Frontiers in immunology, 8, 81. https://doi.org/10.3389/fimmu.2017.00081

Fuster, E., Candela, H., Estévez, J., Arias, A. J., Vilanova, E., and Sogorb, M. A. (2020). Effects of silver nanoparticles on T98G human glioblastoma cells. Toxicology and Applied Pharmacology, 404, 115178. https://doi.org/10.1016/j.taap.2020.115178

Galura, G. M., Chavez, L. O., Robles, A., and McCallum, R. (2019). Gastroduodenal injury: role of protective factors. Current gastroenterology reports, 21, 1-7. https://doi.org/10.1007/s11894-019-0701-x

Ghattamaneni, N. K., Panchal, S. K., and Brown, L. (2019). An improved rat model for chronic inflammatory bowel disease. Pharmacological Reports, 71, 149-155. https://doi.org/10.1016/j.pharep.2018.10.006

Głowacka, U., Magierowski, M., Śliwowski, Z., Cieszkowski, J., Szetela, M., Wójcik-Grzybek, D., Chmura, A., Brzozowski, T., Wallace, J. L., and Magierowska, K. (2023). Hydrogen sulfide-releasing indomethacin-derivative (ATB-344) prevents the development of oxidative gastric mucosal injuries. Antioxidants, 12(8), 1545. https://doi.org/10.3390/antiox12081545

Gu, L., Ge, Z., Wang, Y., Shen, M., and Zhao, P. (2018). Activating transcription factor 3 promotes intestinal epithelial cell apoptosis in Crohn’s disease. Pathology-Research and Practice, 214(6), 862-870. https://doi.org/10.1016/j.prp.2018.04.013

Gyires, K. (2005). Gastric mucosal protection: from prostaglandins to gene therapy. Current medicinal chemistry, 12(2), 203-215. https://doi.org/10.2174/0929867053363478

Hassanein, S. S., Abdel-Mawgood, A. L., and Ibrahim, S. A. (2021). EGFR-dependent extracellular matrix protein interactions might light a candle in the cell behavior of non-small cell lung cancer. Frontiers in Oncology, 11, 766659. https://doi.org/10.3389/fonc.2021.766659

Lingappan, K. (2018). NF-κB in Oxidative Stress. Current Opinion in Toxicology, 7: 81–86. https://doi.org/10.1016/j.cotox.2017.11.002

Liu, D. Y., Gao, L., Zhang, J., Huo, X. W., Ni, H., and Cao, L. (2017). Anti-inflammatory and anti-oxidant effects of licorice flavonoids on ulcerative colitis in mouse model. Chinese Herbal Medicines, 9(4), 358-368. https://doi.org/10.1016/S1674-6384(17)60116-3

Liu, T., Zhang, L., Joo, D., and Sun, S. C. (2017). NF-κB signaling in inflammation. Signal transduction and targeted therapy, 2(1), 1-9. https://doi.org/10.1038/sigtrans.2017.23

Medici, S., Peana, M., Nurchi, V. M., and Zoroddu, M. A. (2019). Medical uses of silver: history, myths, and scientific evidence. Journal of medicinal chemistry, 62(13), 5923-5943. https://doi.org/10.1021/acs.jmedchem.8b01439

Mitchell, J. P., and Carmody, R. J. (2018). NF-κB and the transcriptional control of inflammation. International review of cell and molecular biology, 335, 41-84. https://doi.org/10.1016/bs.ircmb.2017.07.007

Morozova, O. V. (2021). Silver nanostructures: limited sensitivity of detection, toxicity and anti-inflammation effects. International Journal of Molecular Sciences, 22(18), 9928. https://doi.org/10.3390/ijms22189928

Nadworny, P. L., Wang, J., Tredget, E. E., and Burrell, R. E. (2008). Anti-inflammatory activity of nanocrystalline silver in a porcine contact dermatitis model. Nanomedicine: nanotechnology, biology and medicine, 4(3), 241-251. https://doi.org/10.1016/j.nano.2008.04.006

Neurath, M. F. (2014). Cytokines in inflammatory bowel disease. Nature Reviews Immunology, 14(5), 329-342. https://doi.org/10.1038/nri3661

Nowak, M., Madej, J. A., and Dziegiel, P. 2007. Intensity of COX2 expression in cells of soft tissue fibrosarcomas in dogs as related to grade of tumour malignancy. Bulletin of the Veterinary Institute in Pulawy, 51(2), 275.

Nunes, C. D. R., Barreto Arantes, M., Menezes de Faria Pereira, S., Leandro da Cruz, L., de Souza Passos, M., Pereira de Moraes, L., Vieira, I. J. C., and Barros de Oliveira, D. (2020). Plants as sources of anti-inflammatory agents. Molecules, 25(16), 3726. https://doi.org/10.3390/molecules25163726

O’Reilly, L. A., Putoczki, T. L., Mielke, L. A., Low, J. T., Lin, A., Preaudet, A., Heroid, A. J., Yaprianto, K., Tai, L., Kueh, A., Pacinim G,m Ferrero, R. L., Gugasyan, R., Hu, Y., Christie, M., Wilcox, S., Grumont, R., Griffim, M. D. W., O’Connor, L., Smyth, G. K., Ernst, M., Waring, P., Gerondakis, S., and Strasser, A. (2018). Loss of NF-κB1 causes gastric cancer with aberrant inflammation and expression of immune checkpoint regulators in a STAT-1-dependent manner. Immunity, 48(3), 570-583. https://doi.org/10.1016/j.immuni.2018.03.003

Okamoto, C. T., Asano, S., and Sakai, H. (2018). The cell biology of gastric acid secretion. In Physiology of the Gastrointestinal Tract (pp. 831-867). Academic Press. https://doi.org/10.1016/B978-0-12-809954-4.00038-4

Palipoch, S., and Punsawad, C. (2013). Biochemical and histological study of rat liver and kidney injury induced by cisplatin. Journal of Toxicologic Pathology, 26(3), 293-299. https://doi.org/10.1293%2Ftox.26.293

Papoutsopoulou, S., and Campbell, B. J. (2021). Epigenetic modifications of the nuclear factor kappa B signalling pathway and its impact on inflammatory bowel disease. Current Pharmaceutical Design, 27(35), 3702-3713. https://doi.org/10.2174/1381612827666210218141847

Pariente, B., Hu, S., Bettenworth, D., Speca, S., Desreumaux, P., Meuwis, M. A., Danese, S., Rieder, F., and Louis, E. (2019). Treatments for Crohn’s disease–associated bowel damage: a systematic review. Clinical Gastroenterology and Hepatology, 17(5), 847-856. https://doi.org/10.1016/j.cgh.2018.06.043

Park, M. V., Neigh, A. M., Vermeulen, J. P., de la Fonteyne, L. J., Verharen, H. W., Briedé, J. J., Loveren, H. V., and de Jong, W. H. (2011). The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. Biomaterials, 32(36), 9810-9817. https://doi.org/10.1016/j.biomaterials.2011.08.085

Rao, K., Roome, T., Aziz, S., Razzak, A., Abbas, G., Imran, M., Jabri, T., Gul, J., Hussain, M., Sikandar, B., Sharafat, S., and Shah, M. R. (2018). Bergenin-loaded gum xanthan stabilized silver nanoparticles suppress synovial inflammation through modulation of the immune response and oxidative stress in adjuvant-induced arthritic rats. Journal of Materials Chemistry B, 6(27), 4486-4501. https://doi.org/10.1039/C8TB00672E

Sairenji, T., Collins, K. L., and Evans, D. V. (2017). An update on inflammatory bowel disease. Primary Care: Clinics in Office Practice, 44(4), 673-692. https://doi.org/10.1016/j.pop.2017.07.010

Salama, B., Alzahrani, K. J., Alghamdi, K. S., Al-Amer, O., Hassan, K. E., Elhefny, M. A., Albarakati, A. J. A., Alharthi, F., Althagafi, H. A., Al Sberi, H., Amin, H. K., Lokman, M. H., Alsharif, K. F., Albrakati, A., Moneim, A. E. A., Kassab, R. B., and Fathalla, A. S. (2023). Silver nanoparticles enhance oxidative stress, inflammation, and apoptosis in liver and kidney tissues: potential protective role of thymoquinone. Biological trace element research, 201(6), 2942-2954. https://doi.org/10.1007/s12011-022-03399-w

Siczek, K., Zatorski, H., Chmielowiec-Korzeniowska, A., Kordek, R., Tymczyna, L., and Fichna, J. (2017). Evaluation of anti-inflammatory effect of silver-coated glass beads in mice with experimentally induced colitis as a new type of treatment in inflammatory bowel disease. Pharmacological Reports, 69, 386-392. https://doi.org/10.1016/j.pharep.2017.01.003

Singh, S., and Singh, T. G. (2020). Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: a mechanistic approach. Current Neuropharmacology, 18(10), 918-935. https://doi.org/10.2174/1570159X18666200207120949

Sokolova, O., and Naumann, M. (2017). NF-κB signaling in gastric cancer. Toxins, 9(4), 119. https://doi.org/10.3390/toxins9040119

Sousa, A., Bradshaw, T. D., Ribeiro, D., Fernandes, E., and Freitas, M. (2022). Pro-inflammatory effects of silver nanoparticles in the intestine. Archives of Toxicology, 96(6), 1551-1571. https://doi.org/10.1007/s00204-022-03270-w

Szatkowski, P., Krzysciak, W., Mach, T., Owczarek, D., Brzozowski, B., and Szczeklik, K. (2020). Nuclear factor-κB-importance, induction of inflammation, and effects of pharmacological modulators in Crohn's disease. Journal of Physiology & Pharmacology, 71(4). http://dx.doi.org/10.26402/jpp.2020.4.01

Takeuchi, K., and Amagase, K. (2018). Roles of cyclooxygenase, prostaglandin E2 and EP receptors in mucosal protection and ulcer healing in the gastrointestinal tract. Current Pharmaceutical Design, 24(18), 2002-2011. https://doi.org/10.2174/1381612824666180629111227

Taku, K., Britta, S., Chen, W. S., Ferrante, M., Shen, B., Bernstein, C. N., Silvio, D., Laurent, P., and Toshifumi, H. (2020). Ulcerative colitis (primer). Nature Reviews: Disease Primers, 6(1). https://doi.org/10.1038/s41572-020-0205-x

Turkyilmaz, I. B., Coskun, Z. M., Bolkent, S., and Yanardag, R. (2019). The effects of antioxidant combination on indomethacin-induced gastric mucosal injury in rats. Cellular and Molecular Biology, 65(3), 76-83. https://doi.org/10.14715/cmb/2019.65.3.11

Wagner, A., Junginger, J., Lemensieck, F., and Hewicker-Trautwein, M. (2018). Immunohistochemical characterization of gastrointestinal macrophages/phagocytes in dogs with inflammatory bowel disease (IBD) and non-IBD dogs. Veterinary immunology and immunopathology, 197, 49-57. https://doi.org/10.1016/j.vetimm.2018.01.011

Wang, H., Gu, J., Hou, X., Chen, J., Yang, N., Liu, Y., Wang, G., Du, M., Qiu, H., Luo, Y., Jiang, Z., and Feng, L. (2017). Anti-inflammatory effect of miltirone on inflammatory bowel disease via TLR4/NF-κB/IQGAP2 signaling pathway. Biomedicine & Pharmacotherapy, 85, 531-540. https://doi.org/10.1016/j.biopha.2016.11.061

Waranmaselembun, C., Agustiana, A., Firlianty, F., Ngamel, Y. A., and Pratasik, S. B. (2023). Malondialdehyde (MDA) Concentration and Histopathological Image of Indomethacin-Induced Wistar Rat, Rattus norvegicus, With Inflammatory Bowel Disease (IBD) After Mas Ngur Oyster (Atactodea striata) Extract Therapy. Eduvest-Journal of Universal Studies, 3(3), 544-551. https://doi.org/10.59188/eduvest.v3i3.764

Wen, R., Hu, L., Qu, G., Zhou, Q., and Jiang, G. (2016). Exposure, tissue biodistribution, and biotransformation of nanosilver. NanoImpact, 2, 18-28. https://doi.org/10.1016/j.impact.2016.06.001

Yao, D., Dong, M., Dai, C., and Wu, S. (2019). Inflammation and inflammatory cytokines contribute to the initiation and development of ulcerative colitis and its associated cancer. Inflammatory bowel diseases, 25(10), 1595-1602. https://doi.org/10.1093/ibd/izz149

Published

2025-12-17

How to Cite

Putri, C. E. A., Rahmatullah, A. A., Roosdiana, A., & Oktanella, Y. (2025). The Effect of Silver Water (Ag) Administration on NF-κB Expression and Histopathology of Gastric in Rats Model of Inflammatory Bowel Disease. Archives of Veterinary Science, 30(4). https://doi.org/10.5380/avs.v30i4.99059