Regenerative processes during model gastric ulcer in laboratory rats when using Humilid

Keywords: Humilid; Ibuprofen; regeneration; laboratory rats; histological examination; stomach ulcer

Abstract

A gastric ulcer caused by non-steroidal anti-inflammatory drugs is the second most common after Helicobacter pylori in both humane and veterinary medicine. The urgent need to find alternative drugs that had a minimum number of side effects led to the use of a model pathology that mimics a stomach ulcer. The article presents the results of a study of the effect of Humilid on the healing processes of a model gastric ulcer induced by Ibuprofen, a non-steroidal anti-inflammatory drug. The study lasted 21 days. It was found that Ibuprofen at a dose of 400 mg/kg on the 3rd day of the experiment caused damage to the gastric mucosa, namely an ulcer, demonstrated by both macroscopic and histological examination. In the animals of the group where Humilide (5 mg/kg) was used against the background of Ibuprofen-induced ulcers, on day 21 of the experiment, the ulcer score (Ulcer score) was 94% lower (P <0.001) compared to the ulcer score of the same group by 3 - e day of the experiment. And in animals of the group where the ulcer was formed, but Gumilid was not used, the difference in ulcer scores on day 21 of the experiment was 81% (P <0.001) compared to the ulcer score in rats receiving Humilid. A histological study showed that in animals of the group receiving Humilid, such indicators as desquamation of the epithelium, erosive and ulcerative destruction, stromal oedema and inflammatory infiltration were 56%, 62%, 30% and 60% (P <0.001) lower, respectively, compared to with a group of model pathology, where it was not received. Thus, it was found that with Ibuprofen-induced gastric ulcer, including Humilide in the general diet of animals in the experimental group, accelerates and improves regenerative processes, namely, the healing of stomach ulcers.

Downloads

Download data is not yet available.

References

Adinortey, M. B., Ansah, C., Galyuon, I., & Nyarko, A. (2013). In vivo models used for evaluation of potential antigastroduodenal ulcer agents. Ulcers, 2013, 1–12.

Aeschbacher, M., Graf, C., Schwarzenbach, R. P., & Sander, M. (2012). Antioxidant Properties of Humic Substances. Environmental Science & Technology, 46(9), 4916–4925.

Ajayi, A. F., & Olaleye, B. S. (2020). Age-related changes in haematological parameters and biochemical markers of healing in the stomach of rats with acetic acid induced injury. Toxicology Reports, 7, 1272–1281.

Almasaudi, S. B., El-Shitany, N. A., Abbas, A. T., Abdel-dayem, U. A., Ali, S. S., Al Jaouni, S. K., & Harakeh, S. (2016). Antioxidant, anti-inflammatory, and antiulcer potential of manuka honey against gastric ulcer in rats. Oxidative Medicine and Cellular Longevity, 2016, 1–10.

Amosova, Ya. M., Kosyanova, Z. F., Orlov, D. S., Tikhomirova, K. S., & Shinkarenko, A. L. (1990). Humic acids in the therapeutic muds with a special reference to their physiological activity. Kurortol. Fizioter, 27(4), 1–6.

Anselmo, A. C., Gokarn, Y., & Mitragotri, S. (2018). Non-invasive delivery strategies for biologics. Nature Reviews Drug Discovery, 18(1), 19–40.

Ansorg, R., & Rochus, W. (1978). Untersuchungen zur antimikrobiellen Wirksamkeit von natürlichen und künstlichen Huminsäuren [Studies on the antimicrobial effect of natural and synthetic humic acids (author’s transl)]. Arzneimittel-Forschung, 28(12), 2195–2198.

Appleyard, C. B., & Wallace, J. L. (1995). Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugs. American Journal of Physiology-Gastrointestinal and Liver Physiology, 269(1), 119–125.

Arnold, D. M., Kukaswadia, S., Nazi, I., Esmail, A., Dewar, L., Smith, J. W., & Kelton, J. G. (2013). A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. Journal of Thrombosis and Haemostasis, 11(1), 169–176.

Aruin, L. I., Kapuller, L. L., & Isakov, V. A. (1998). Mofologicheskaja diagnostika boleznej zheludka i kishechnika. Triada-H. Moscow, 125–130 (in Russian).

Bergh, M. S., & Budsberg, S. C. (2005). The coxib NSAIDs: potential clinical and pharmacologic importance in veterinary medicine. Journal of Veterinary Internal Medicine, 19(5),633–643.

Bhargava, K. P., Gupta, M. B., & Tangri, K. K. (1973). Mechanism of ulcerogenic activity of indomethacin and oxyphenbutazone. European Journal of Pharmacology, 22(2), 191–195.

Bi, W.-P. (2014). Efficacy and safety of herbal medicines in treating gastric ulcer: A review. World Journal of Gastroenterology, 20(45), 17020–17028.

Blandizzi, C., Fornai, M., Colucci, R., Natale, G., Lubrano, V., Vassalle, C., Antonioli, L., Lazzeri, G., & Del Tacca, M. (2005). Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage. World Journal of Gastroenterology, 11(26), 4052–4060.

Boeing, T., da Silva, L. M., Somensi, L. B., Cury, B. J., Michels Costa, A. P., Petreanu, M., Niero, R., & de Andrade, S. F. (2016). Antiulcer mechanisms of Vernonia condensata Baker: A medicinal plant used in the treatment of gastritis and gastric ulcer. Journal of Ethnopharmacology, 184, 196–207.

Buchko, O. (2014). Vil’noradykal’ni procesy j antyoksydantna systema organizmu svynej za dii’ guminovoi’ dobavky. Visnyk Lvivskogo Universytetu, 64, 90–96 (in Ukrainian).

Çalışır, M., Akpınar, A., Talmaç, A. C., Lektemur Alpan, A., & Göze, Ö. F. (2018). Humic acid enhances wound healing in the rat palate. Evidence-Based Complementary and Alternative Medicine, 1(1), 1–6.

Cantarella, G., Martinez, G., Cutuli, V. M., Loreto, C., D’Alcamo, M., Prato, A., Amico-Roxas, M., Bernardini, R., & Clementi, G. (2005). Adrenomedullin modulates COX-2 and HGF expression in reserpine-injuried gastric mucosa in the rat. European Journal of Pharmacology, 518(2-3), 221–226.

Cantarella, G., Martinez, G., Di Benedetto, G., Loreto, C., Musumeci, G., Prato, A., Lempereur, L., Matera, M., Amico-Roxas, M., Bernardini, R., & Clementi, G. (2007). Protective effects of amylin on reserpine-injured gastric damage in the rat. Pharmacological Research, 56, 27–34.

Coruzzi, G., Menozzi, A., & Dobrilla, G. (2004). Novel non-steroidal anti-inflammatory drugs: what we have learned from animal studies. Current Drug Target -Inflammation & Allergy, 3(1), 43–61.

Diachenko, L. M., & Stepchenko, L. M. (2018). Erythrocyte system of rat blood during the application of fodder additives of humic nature for combined stress. Theoretical and Applied Veterinary Medicine, 6(3), 34–38.

Djahanguiri, B. (1969). The production of acute gastric ulceration by indomethacin in the rat. Scandinavian Journal of Gastroenterology, 4(3), 265–267.

Dyomshina, O. O., Ushakova, G. O., & Stepchenko, L. M. (2017). The effect of biologically active feed additives of humilid substances on the antioxidant system in liver mitochondria of gerbils. Regulatory Mechanisms in Biosystems, 8(2), 185–190.

Dyomshyna, O.O., Stepchenko, L.M., Ushakova, G. (2021). The impact of the humate nature feed additives on the antioxidative status of erythrocytes, liver, and muscle in chickens, hens, and gerbils. Biointerface Research in Applied Chemistry, 11(5), 13202–13213.

Fazalda, A., Quraisiah, A., & Nur Azlina, M. F. (2018). Antiulcer effect of honey in nonsteroidal anti-inflammatory drugs induced gastric ulcer model in rats: A systematic review. Evidence-Based Complementary and Alternative Medicine, 2018, 1–12.

Fulga, S., Pelin, A.-M., Ghiciuc, C. M., & Lupușoru, E. C. (2019). Particularities of experimental models used to induce gastric ulcer. ARS Medica Tomitana, 25(4), 179–184.

Galati, G., Tafazoli, S., Sabzevari, O., Chan, T. S., & O’Brien, P. J. (2002). Idiosyncratic NSAID drug induced oxidative stress. Chemico-Biological Interactions, 142(1-2), 25–41.

Ghasemkhani, N., Tabrizi, A. S., Namazi, F., & Nazifi, S. (2021). Treatment effects of Shilajit on aspirin-induced gastric lesions in rats. Physiological Reports, 9(7).

Golbs, S., & Kühnert, M. (1983). Huminsäuren - anwendung in therapie, pro- und metaphylaxe in der veterinärmedizin1. physikalische medizin, rehabilitationsmedizin, Kurortmedizin, 35(03), 151–158.

Guo S, Di Pietro LA, 2006. Factors affecting wound healing. J Dent Res., 89: 219-29.

Gurel, S. G., Sogut, I., Hurdag, C., Gurel, A., Tutar, A., & Cikler-Dulger, E. (2021). Effect of fulvic acid on gastric mucosa damage caused by chronic water avoidance stress. Biotechnic & Histochemistry, 1–8.

Harashchuk, M. I., Stepchenko, L. M., Spitsina, T. L., & Goryaniy, V. R. (2021). Metabolism state in laboratory rats when using amaranth oil and Humilid. Theoretical and Applied Veterinary Medicine, 9(1), 30–34.

Hayllar, J., & Bjarnason, I. (1995). NSAIDs, Cox-2 inhibitors, and the gut. The Lancet, 346(8974), 521–522.

Hernandez-Diaz, S. (2001). Steroids and Risk of Upper Gastrointestinal Complications. American Journal of Epidemiology, 153(11), 1089–1093.

Horalskiy, L. P., Khomych, V. T., & Kononsky, A. I. (2019). Histological techniques and morphological methods in normal and pathological conditions. Zhitomir, Polissia (in Ukrainian).
Hullár, I., Vucskits, A. V., Berta, E., Andrásofszky, E., Bersényi, A., & Szabó, J. (2018). Effect of fulvic and humic acids on copper and zinc homeostasis in rats. Acta Veterinaria Hungarica, 66(1), 40–51.

Iismaa, S. E., Kaidonis, X., Nicks, A. M., Bogush, N., Kikuchi, K., Naqvi, N., & Graham, R. M. (2018). Comparative regenerative mechanisms across different mammalian tissues. Npj Regenerative Medicine, 3(1), 1–6.

Jainu, M., & Devi, C. S. S. (2004). Antioxidant effect of methanolic extract ofSolanum nigrum berries on aspirin induced gastric mucosal injury. Indian Journal of Clinical Biochemistry, 19(1), 57–61.

Ji, Y., Zhang, A., Chen, X., Che, X., Zhou, K., & Wang, Z. (2016). Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats. Acta Pharmaceutica Sinica B, 6(2), 132–140.

Jooné, G. K., & van Rensburg, C. E. J. (2004). An in vitro investigation of the anti-inflammatory properties of potassium humate. Inflammation, 28(3), 169–174.

Kim, Y.-S., Park, H. J., Kim, H., Song, J., & Lee, D. (2019). Gastroprotective effects of Paeonia extract mixture HT074 against experimental gastric ulcers in rats. Evidence-Based Complementary and Alternative Medicine, 1–13.

Kim, J. H., Kim, B. W., Kwon, H. J., & Nam, S. W. (2011). Curative effect of selenium against indomethacin-induced gastric ulcers in rats. Journal of Microbiology and Biotechnology, 21(4), 400–404.

Klavins, M., & Purmalis, O. (2009). Humic substances as surfactants. Environmental Chemistry Letters, 8(4), 349–354.

Klein, O. I., Kulikova, N. A., Konstantinov, A. I., Zykova, M. V., & Perminova, I. V. (2021). A Systematic Study of the Antioxidant Capacity of Humic Substances against Peroxyl Radicals: Relation to Structure. Polymers, 13(19), 3262.

Klöcking, R., & Helbig, B. (2001). Humic substances, medical aspects and applications of humic substances. Biopolymers Online, 3–16.

Kopp, J. L., Grompe, M., & Sander, M. (2016). Stem cells versus plasticity in liver and pancreas regeneration. Nature Cell Biology, 18(3), 238–245.

Lamarque, D. (2004). Pathogenesis of gastroduodenal lesions induced by non-steroidal anti-inflammatory drugs. Gastroenterologie Clinique et Biologique, 28, 18–26.

Lim, J.-M., Song, C.-H., Park, S.-J., Park, D.-C., Jung, G.-W., Cho, H.-R., & Choi, J.-S. (2019). Protective effects of triple fermented barley extract (FBe) on indomethacin-induced gastric mucosal damage in rats. BMC Complementary and Alternative Medicine, 19(49), 1–11.

MacAllister, C. G., Andrews, F. M., Deegan, E., Ruoff, W., & Olovson, S. G. (1997). A scoring system for gastric ulcers in the horse. Equine Veterinary Journal, 29, 430–433.

Mescher, A. L. (2017). Macrophages and fibroblasts during inflammation and tissue repair in models of organ regeneration. Regeneration, 4(2), 39–53.

Monteiro-Steagall, B. P., Steagall, P. V. M., & Lascelles, B. D. X. (2013). Systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs. Journal of Veterinary Internal Medicine, 27(5), 1011–1019.

Muhammad, N., Saeed, M., Khan, A., Adhikari, A., Wadood, A., Khan, K., & De Feo, V. (2014). A new urease inhibitor from Viola betonicifolia. Molecules, 19(10), 16770–16778.

Oosterhuis, W. P., Niessen, R. W. L. M., Bossuyt, P. M. M., Sanders, G. T. B., & Sturk, A. (2000). Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency. Scandinavian Journal of Clinical and Laboratory Investigation, 60(1), 9–18.

Rainsford, K. D. (1987). The effects of 5-lipoxygenase inhibitors and leukotriene antagonists on the development of gastric lesions induced by nonsteroidal antiinflammatory drugs in mice. Agents and Actions, 21(3-4), 316–319.

Rao, C. V., Sairam, K., & Goel, R. K. (2000). Experimental evaluation of Bocopa monniera on rat gastric ulceration and secretion. Indian Journal of Physiology and Pharmacology, 44(4), 435–441.

Salim, A. S. (1992). Use of scavenging oxygen-derived free radicals to protect the rat against aspirin- and ethanol-induced erosive gastritis. Journal of Pharmaceutical Sciences, 81(9), 943–946.

Saxena, A., Balaramnavar, V. M., Hohlfeld, T., & Saxena, A. K. (2013). Drug/drug interaction of common NSAIDs with antiplatelet effect of aspirin in human platelets. European Journal of Pharmacology, 721, 215–224.

Schafer, M., & Werner, S. (2008). Oxidative stress in normal and impaired wound repair. Pharmacological Research, 58(2), 165–171.

Schewe, C., Klöcking, R., Helbig, B., & Schewe, T. (1991). Lipoxygenase-inhibitory action of antiviral polymeric oxidation products of polyphenols. Biomedica Biochimica Acta, 50, 299–305.

Simões, S., Lopes, R., Campos, M. C. D., Marruz, M. J., da Cruz, M. E. M., & Corvo, L. (2019). Animal models of acute gastric mucosal injury: Macroscopic and microscopic evaluation. Animal Models and Experimental Medicine, 2(2), 121–126.

Stepchenko, L. M., & Skorik, M. V. (2006). Condition of erythrocyte antioxidant laying hens for the actions of humic substances. Technical bulletin Scientific Institute of Animal Biology and State Research Control Institute of Veterinary Preparations and Feed Additives, 7(3–4), 137–143 (in Ukrainian).

Stepchenko, L. M., Kryvaya, O. A., & Chumak, V. O. (2019). Determination of the level of safety of Humilid during biotesting at ciliates. Theoretical and Applied Veterinary Medicine, 7(4), 210–214.

Stepchenko, L. M. (2005). Mehanyzmy formyrovanyja byoprodukcyy u bystrorastushhej ptycy pod vlyjanyem preparatov gumynovoj pryrody. Visnyk Dnipropetrovs’kogo Derzhavnogo Agrarnogo Universytetu, 2, 237–241 (in Ukrainian).

Suleyman, H., Albayrak, A., Bilici, M., Cadirci, E., & Halici, Z. (2010). Different mechanisms in formation and prevention of indomethacin-induced gastric ulcers. Inflammation, 33(4), 224–234.

Szabó, J., Vucskits, A. V., Berta, E., Andrásofszky, E., Bersényi, A., & Hullár, I. (2017). Effect of fulvic and humic acids on iron and manganese homeostasis in rats. Acta Veterinaria Hungarica, 65(1), 66–80.

Szpirer, C. (2020). Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes. Journal of Biomedical Science, 27(1), 84.

Tikhonov, V. V., Yakushev, A. V., Zavgorodnyaya, Y. A., Byzov, B. A., & Demin, V. V. (2010). Effects of humic acids on the growth of bacteria. Eurasian Soil Science, 43(3), 305–313.

Trckova, M., Matlova, L., Hudcova, H., Faldyna, M., Zraly, Z., Dvorska, L., & Pavlik, I. (2012). Peat as a feed supplement for animals: a literature review. Veterinární Medicína, 50(8), 361–377.

Upadhyay, R., Torley, H. I., McKinlay, A. W., Sturrock, R. D., & Russell, R. I. (1990). Iron deficiency anaemia in patients with rheumatic disease receiving non-steroidal anti-inflammatory drugs: the role of upper gastrointestinal lesions. Annals of the Rheumatic Diseases, 49(6), 359–362.

Van Rensburg, C. E. J. (2000). An in vitro investigation of the antimicrobial activity of oxifulvic acid. Journal of Antimicrobial Chemotherapy, 46(5), 853–854.

Van Rensburg, C. E. J. (2015). The antiinflammatory properties of humic substances: A mini review. Phytotherapy Research, 29(6), 791–795.

Vannella, K. M., & Wynn, T. A. (2017). Mechanisms of organ injury and repair by macrophages. Annual Review of Physiology, 79(1), 593–617.

Vucskits, A. V., Hullár, I., Bersényi, A., Andrásofszky, E., Kulcsár, M., & Szabó, J. (2010). Effect of fulvic and humic acids on performance, immune response and thyroid function in rats. Journal of Animal Physiology and Animal Nutrition, 94(6), 721–728.

Wallace, J. L., McKnight, W., Reuter, B. K., & Vergnolle, N. (2000). NSAID-induced gastric damage in rats: Requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology, 119(3), 706–714.

Wallace, J. L. (2008). Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? Physiological Reviews, 88(4), 1547–1565.

Werawatganon, D., Lakananurak, N., Sallapant, S., Prueksapanich, P., Somanawat, K., Wisedopas, N., & Rerknimitr, R. (2014). Su1959 Aloe Vera attenuated gastric injury on indomethacin-induced gastropathy in rats. Gastroenterology, 146(5), 18330–18337.

Whittle, B. J. R. (2003). Gastrointestinal effects of nonsteroidal anti-inflammatory drugs. Fundamental & Clinical Pharmacology, 17(3), 301–313.

Wolfe, M. M., Lichtenstein, D. R., & Singh, G. (1999). Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. New England Journal of Medicine, 340(24), 1888–1899.

Zaghlool, S. S., Abo-Seif, A. A., Rabeh, M. A., Abdelmohsen, U. R., & Messiha, B. A. S. (2019). Gastro-protective and anti-oxidant potential of Althaea officinalis and Solanum nigrum on Pyloric Ligation/indomethacin-induced ulceration in rats. Antioxidants, 8(11), 512.

Zykova, M., Schepetkin, I., Belousov, M., Krivoshchekov, S., Logvinova, L., Bratishko, K., Yusubov, M. S., Romanenko, S. V., & Quinn, M. T. (2018). Physicochemical characterization and antioxidant activity of humic acids isolated from Peat of Various Origins. Molecules, 23(4), 753.

Abstract views: 85
PDF Downloads: 57
Published
2021-12-20
How to Cite
Lisna, A. Y., & Stepchenko, L. M. (2021). Regenerative processes during model gastric ulcer in laboratory rats when using Humilid. Theoretical and Applied Veterinary Medicine, 9(4), 173-181. https://doi.org/10.32819/2021.94026