Sıçanlarda Etanol ile İndüklenen Gastrik Ülser Modelinde Idebenon ve Krisinin Koruyucu Etkileri
Year 2025,
Volume: 5 Issue: 1, 30 - 37, 17.03.2025
Arzu Gezer
,
Ali Sefa Mendil
,
Gürsel Bedir
,
Hilal Üstündağ
Abstract
Bu çalışmada, sıçanlarda etanol ile indüklenen gastrik ülsere karşı idebenon ve krisinin koruyucu etkileri araştırılmıştır. Yirmi sekiz Sprague-Dawley erkek sıçan dört gruba ayrılmıştır: 1 ml serum fizyolojik alan kontrol grubu, gastrik ülser indüklemek için etanol (ET) (5 ml/kg) alan ET grubu ve iki tedavi grubu; biri ET'yi takiben idebenon (200 mg/kg), diğeri ET'yi takiben krisin (100 mg/kg) alan gruplar. Tedaviler oral gavaj yoluyla uygulanmıştır. Gastrik mukozal hasarı ve tedavilerin koruyucu mekanizmasını değerlendirmek için, somatostatin ve aquaporin-1 düzeylerine odaklanan histopatolojik incelemeler ve immünohistokimyasal analizler gerçekleştirilmiştir. Histopatolojik incelemelerde, ET ile muamele edilen grupta şiddetli dejeneratif ve nekrotik değişiklikler gözlenmiştir. Sonuçlar, tedavi gruplarında gastrik mukozal hasarın ET grubuna kıyasla önemli ölçüde azaldığını ve nekrotik lezyonların şiddetinde anlamlı bir azalma olduğunu göstermiştir. Kantitatif analiz, tedavi gruplarında somatostatin ve aquaporin-1 ekspresyonunda anlamlı bir artış olduğunu ortaya koymuştur (P < 0,05), bu da artmış gastrik mukozal savunmayı göstermektedir. İdebenon ve krisinin, ET ile indüklenen gastrik ülserlerde histopatolojik hasarı önemli ölçüde azalttığı ve somatostatin ile aquaporin-1 ekspresyonunu artırdığı bulunmuştur. Nekrotik lezyonlardaki azalma ve gastrik mukozal savunma mekanizmalarının güçlenmesi, idebenon ve krisinin gastrik ülserlerin önlenmesi ve tedavisi için terapötik potansiyel sunabileceğini düşündürmektedir.
References
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Chrysin modulates genes related to inflammation, tissue remodeling, and cell proliferation in the gastric ulcer healing. International journal of molecular sciences, 21(3), 760. https://doi.org/10.3390/ijms21030760
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- Liao, S., Gan, L., Lv, L., & Mei, Z. (2021). The regulatory roles of aquaporins in the digestive system. Genes & Diseases, 8(3), 250-258. https://doi.org/10.1016/j.gendis.2019.12.011
- Mazzoni, M., Lattanzio, G., Bonaldo, A., Tagliavia, C., Parma, L., Busti, S., Gatta, P. P., Bernardi, N., & Clavenzani, P. (2021). Effect of essential oils on the oxyntopeptic cells and somatostatin and ghrelin immunoreactive cells in the european sea bass (Dicentrarchus labrax) gastric mucosa. Animals, 11(12), 3401. https://doi.org/10.3390/ani11123401
- Naz, S., Imran, M., Rauf, A., Orhan, I. E., Shariati, M. A., Shahbaz, M., Qaisrani, T. B., Shah, Z. A., Plygun, S., & Heydari, M. (2019). Chrysin: Pharmacological and therapeutic properties. Life sciences, 235, 116797. https://doi.org/10.1016/j.lfs.2019.116797
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- Shastri, S., Shinde, T., Sohal, S. S., Gueven, N., & Eri, R. (2020). Idebenone protects against acute murine colitis via antioxidant and anti-inflammatory mechanisms. International Journal of Molecular Sciences, 21(2), 484. https://doi.org/10.3390/ijms21020484
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- Şimşek, H., Akaras, N., Gür, C., Küçükler, S., & Kandemir, F. M. (2023). Beneficial effects of Chrysin on Cadmium‐induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO‐1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene, 875, 147502. https://doi.org/10.1016/j.gene.2023.147502
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THE PROTECTIVE EFFECTS OF IDEBENONE AND CHRYSIN ON ETHANOL-INDUCED GASTRIC ULCER IN RATS
Year 2025,
Volume: 5 Issue: 1, 30 - 37, 17.03.2025
Arzu Gezer
,
Ali Sefa Mendil
,
Gürsel Bedir
,
Hilal Üstündağ
Abstract
Objective: In this study, the protective effects of idebenone and chrysin against ethanol-induced gastric ulcers in rats were investigated.
Material and methods: Twenty-eight Sprague-Dawley male rats were categorized into four groups: a control group receiving 1 ml saline, an ethanol (ET) group receiving ET (5 ml/kg) to induce gastric ulcers, and two treatment groups, one receiving ET followed by idebenone (200 mg/kg) and the other receiving ET followed by chrysin (100 mg/kg). Treatments were administered orally via gavage. Histopathological examinations and immunohistochemical analyses focusing on somatostatin and aquaporin-1 levels were performed to evaluate gastric mucosal damage and the protective mechanism of the treatments.
Results: In histopathological examinations, severe degenerative and necrotic changes were observed in the ET treated group. The results showed that gastric mucosal damage was significantly reduced in the treatment groups compared to the ET group and there was a significant reduction in the severity of necrotic lesions. Quantitative analysis revealed a significant increase in somatostatin and aquaporin-1 expression in the treatment groups (P < 0.05), indicating increased gastric mucosal defence.
Conclusion: Idebenone and chrysin were found to significantly mitigate histopathological damage and increase the expression of somatostatin and aquaporin-1 in ET-induced gastric ulcers. The reduction in necrotic lesions and enhancement of gastric mucosal defense mechanisms suggest that idebenone and chrysin may offer therapeutic potential for the prevention and treatment of gastric ulcers.
Ethical Statement
Ethical approval was obtained from the Ataturk University Animal Experiments Local Ethics Committee under the decision dated February 26, 2024, and desicion number 2024/43.
References
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- Baykalir, B. G., Arslan, A. S., Mutlu, S. I., Ak, T. P., Seven, I., Seven, P. T., Yaman, M., & Gul, H. F. (2020). The protective effect of chrysin against carbon tetrachloride-induced kidney and liver tissue damage in rats. International Journal for Vitamin and Nutrition Research. https://doi.org/10.1024/0300-9831/a000653
- Bodis, B., Nagy, G., Németh, P., & Mózsik, G. (2001). Active water selective channels in the stomach: investigation of aquaporins after ethanol and capsaicin treatment in rats. Journal of Physiology-Paris, 95(1-6), 271-275. https://doi.org/10.1016/S0928-4257(01)00037-7
- Bogdanov, S. (2012). Pollen: Nutrition, functional properties, health. Magnesium, 20, 350.
- Cores, Á., Carmona-Zafra, N., Clerigué, J., Villacampa, M., & Menéndez, J. C. (2023). Quinones as neuroprotective agents. Antioxidants, 12(7), 1464. https://doi.org/10.3390/antiox12071464
- Fagundes, F. L., Piffer, G. d. M., Périco, L. L., Rodrigues, V. P., Hiruma-Lima, C. A., & Dos Santos, R. d. C. (2020).
Chrysin modulates genes related to inflammation, tissue remodeling, and cell proliferation in the gastric ulcer healing. International journal of molecular sciences, 21(3), 760. https://doi.org/10.3390/ijms21030760
- George, M. Y., Esmat, A., Tadros, M. G., & El-Demerdash, E. (2018). In vivo cellular and molecular gastroprotective mechanisms of chrysin; Emphasis on oxidative stress, inflammation and angiogenesis. European Journal of Pharmacology, 818, 486-498. https://doi.org/10.1016/j.ejphar.2017.11.008
- Gezer, A., Laloglu, A., & Bölükbaş, M. K. (2023). Protective Effects of Alpha Lipoic Acid Against Ionizing Radiation-Induced Hepatotoxicity in Rats. The Eurasian Journal of Medicine, 55(2), 104. https://doi.org/10.5152/eurasianjmed.2023.0148
- Gezer, A., & Sari, E. K. (2023). Investigation of apoptotic and autophagic effects of chronic roflumilast use on testicular tissue in rats by immunohistochemical and immunofluorescence methods. Iranian Journal of Basic Medical Sciences, 26(3), 276. https://doi.org/10.22038/IJBMS.2023.65948.14507
- Hardin, J., Wallace, L., Wong, J., O’loughlin, E., Urbanski, S., Gall, D., MacNaughton, W., & Beck, P. (2004). Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn’s disease and infectious colitis. Cell and tissue research, 318(2), 313-323. https://doi.org/10.1007/s00441-004-0932-4
- Inatsu, S., Ohsaki, A., & Nagata, K. (2006). Idebenone acts against growth of Helicobacter pylori by inhibiting its respiration. Antimicrobial agents and chemotherapy, 50(6), 2237-2239. https://doi.org/10.1128/aac.01118-05
- İpek, B. E., Yüksel, M., Cumbul, A., Ercan, F., Cabadak, H., Aydın, B., & Alican, İ. (2022). The effect of metformin on ethanol-and Indomethacin-Induced gastric ulcers in rats. The Turkish Journal of Gastroenterology, 33(9), 767. https://doi.org/10.5152/tjg.2022.21195
- Kaya, C. (2022). Sıçanlarda indometazin ile indüklenen mide ülseri üzerine idebenon'un etkilerinin araştırılması Tekirdağ Namık Kemal Üniversitesi.
- Kim, D.-U., Na, J. Y., Paik, S. S., Jee, S., Lee, Y. H., & Kim, Y. J. (2023). Mucosal distribution of somatostatin-secreting gastric Delta cells in children with gastrointestinal reflux diseases. Frontiers in Pediatrics, 11. https://doi.org/10.3389/fped.2023.1275842
- Kim, M., Hwang, I. Y., Lee, J.-H., Son, K. H., Jeong, C.-S., & Jung, J. (2011). Protective effect of Cimicifuga heracleifolia ethanol extract and its constituents against gastric injury. Journal of Health Science, 57(3), 289-292. https://doi.org/10.1248/jhs.57.289
- Küçükler, S., Kandemir, F. M., & Yıldırım, S. (2022). Protective effect of chrysin on indomethacin induced gastric ulcer in rats: role of multi-pathway regulation. Biotechnic & Histochemistry, 97(7), 490-503. https://doi.org/10.1080/10520295.2021.2014569
- Liao, S., Gan, L., Lv, L., & Mei, Z. (2021). The regulatory roles of aquaporins in the digestive system. Genes & Diseases, 8(3), 250-258. https://doi.org/10.1016/j.gendis.2019.12.011
- Mazzoni, M., Lattanzio, G., Bonaldo, A., Tagliavia, C., Parma, L., Busti, S., Gatta, P. P., Bernardi, N., & Clavenzani, P. (2021). Effect of essential oils on the oxyntopeptic cells and somatostatin and ghrelin immunoreactive cells in the european sea bass (Dicentrarchus labrax) gastric mucosa. Animals, 11(12), 3401. https://doi.org/10.3390/ani11123401
- Naz, S., Imran, M., Rauf, A., Orhan, I. E., Shariati, M. A., Shahbaz, M., Qaisrani, T. B., Shah, Z. A., Plygun, S., & Heydari, M. (2019). Chrysin: Pharmacological and therapeutic properties. Life sciences, 235, 116797. https://doi.org/10.1016/j.lfs.2019.116797
- Oncel, S., & Basson, M. D. (2022). Gut homeostasis, injury, and healing: New therapeutic targets. World Journal of Gastroenterology, 28(17), 1725. https://doi.org/10.3748/wjg.v28.i17.1725
- Serafim, C., Araruna, M. E., Júnior, E. A., Diniz, M., Hiruma-Lima, C., & Batista, L. (2020). A review of the role of flavonoids in peptic ulcer (2010–2020). Molecules, 25(22), 5431. https://doi.org/10.3390/molecules25225431
- Shastri, S., Shinde, T., Perera, A. P., Gueven, N., & Eri, R. (2020). Idebenone protects against spontaneous chronic murine colitis by alleviating endoplasmic reticulum stress and inflammatory response. Biomedicines, 8(10), 384. https://doi.org/10.3390/biomedicines8100384
- Shastri, S., Shinde, T., Sohal, S. S., Gueven, N., & Eri, R. (2020). Idebenone protects against acute murine colitis via antioxidant and anti-inflammatory mechanisms. International Journal of Molecular Sciences, 21(2), 484. https://doi.org/10.3390/ijms21020484
- Suárez-Rivero, J. M., Pastor-Maldonado, C. J., Povea-Cabello, S., Álvarez-Córdoba, M., Villalón-García, I., Munuera-Cabeza, M., Suárez-Carrillo, A., Talaverón-Rey, M., & Sánchez-Alcázar, J. A. (2021). Coenzyme Q10 analogues: Benefits and challenges for therapeutics. Antioxidants, 10(2), 236. https://doi.org/10.3390/antiox10020236
- Şimşek, H., Akaras, N., Gür, C., Küçükler, S., & Kandemir, F. M. (2023). Beneficial effects of Chrysin on Cadmium‐induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO‐1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene, 875, 147502. https://doi.org/10.1016/j.gene.2023.147502
- Toktay, E., & Selli, J. (2022). Histopathological Overview of Experimental Ulcer Models. https://doi.org/10.5152/eurasianjmed.2022.22312
- Yaghoobi, M., & Armstrong, D. (2022). Peptic ulcer disease. Yamada's Textbook of Gastroenterology, 924-976. https://doi.org/10.1002/9781119600206.ch49
- Ye, Y., Ran, J., Yang, B., & Mei, Z. (2023). Aquaporins in Digestive System. In Aquaporins. Springer, 145-154. https://doi.org/10.1007/978-981-19-7415-1_10
- Zhou, D., Yang, Q., Tian, T., Chang, Y., Li, Y., Duan, L.-R., Li, H., & Wang, S.-W. (2020). Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role. Biomedicine & Pharmacotherapy, 126, 110075. https://doi.org/10.1016/j.biopha.2020.110075