Sıçanlarda etanol kaynaklı gastrik ülser modelinde peroral kapsaisin uygulamasının koruyucu etkisi
Yıl 2025,
Cilt: 64 Sayı: 1, 98 - 106, 12.03.2025
Mete Keçeci
,
Meryem Akpolat Ferah
,
Habib Khoshvaghti
,
Osman Cengil
Öz
Amaç: Kapsaisin, hemen tüm acı biberlerin yapısında bulunan anti-oksidan ve anti-inflamatuar özelliklere sahip bir bileşiktir. Çalışmamızda etanolik ülser modelinde kapsaisin’in koruyucu etkisi araştırılmıştır.
Gereç ve Yöntem: Erkek Wistar albino sıçanlar biri kontrol üçü deney grubu olmak üzere dört gruba ayrılmıştır (n=8). Kontrol (C) grubuna tek doz distile su subkutan uygulanmıştır. Kapsaisin (CAP) grubuna tek doz 1 mg/kg CAP gavaj yoluyla uygulanmıştır. Ülser (U) grubuna tek doz distile suyun gavaj yoluyla uygulanmasından 30 dakika sonra tek doz 1 ml mutlak alkol gavaj yoluyla uygulanmıştır. U+CAP grubuna 1 mg/kg CAP uygulanmasından 30 dakika sonra 1 ml mutlak alkol uygulanmıştır. Çıkarılan mide dokularında makroskobik ve mikroskobik ülser skorları ve mukozal bariyer bütünlüğü değerlendirilmiştir. Dokuda total oksidan status (TOS) ve total anti-oksidan status (TAS) seviyeleri ölçülmüş ve oksidatif stres indeksi (OSI) hesaplanmıştır.
Bulgular: U grubuyla karşılaştırıldığında, makroskobik ve mikroskobik mukozal lezyonlar, TOS, OSI seviyeleri ve IL-1, TNF-α, NFκB ve Kaspaz 3 ekspresyonlarının U+CAP grubunda azaldığı, ancak TAS seviyesinin arttığı görülmüştür.
Sonuç: Çalışma, kapsaisin'in etanol kaynaklı gastrik ülser modelinde anti-oksidan, anti-inflamatuar ve anti-apoptotik özellikleriyle mukozal bütünlüğü koruduğunu göstermiştir.
Etik Beyan
Çalışma, ABD Halk Sağlığı Servisi tarafından yayınlanan Laboratuvar Hayvanlarının Bakımı ve Kullanımı Kılavuzu'nda belirtilen yönergelere uygun olarak yürütüldü. Çalışmaya başlamadan önce Bülent Ecevit Üniversitesi Kurumsal Hayvan Etik Kurulu'ndan (Zonguldak, Türkiye; 2020-06-27/02) onay alındı.
Destekleyen Kurum
Zonguldak Bülent Ecevit Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü
Proje Numarası
2020-98210206-01
Kaynakça
- Lin KJ, García Rodríguez LA, Hernández-Díaz S. Systematic review of peptic ulcer disease incidence rates:
do studies without validation provide reliable estimates? Pharmacoepidemiol Drug Saf. 2011;20(7):718-28.
- Del Valle J. Chapter 324: Peptic Ulcer Disease and Related Disorders. In: Loscalzo J, Fauci A, Kasper D,
Hauser S, Longo D, Jameson J, editors. Harrisons Principles of Internal Medicine, 21e. McGraw Hill; 2022.
- Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, et al. Smoking, alcohol consumption, and 24
gastrointestinal diseases: Mendelian randomization analysis. eLife. 2023;12:e84051.
- Zhou D, Yang Q, Tian T, Chang Y, Li Y, Duan LR, et al. Gastroprotective effect of gallic acid against ethanol-
induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role. Biomed
Pharmacother. 2020;126:110075.
- Orona-Ortiz A, Velázquez-Moyado JA, Pineda-Peña EA, Balderas-López JL, Tavares Carvalho JC, Navarrete
A. Effect of the proportion of curcuminoids on the gastroprotective action of Curcuma longa L. in rats. Nat
Prod Res. 2021;35(11):1903-8.
- Chang A, Rosani A, Quick J. Capsaicin. In: StatPearls. StatPearls Publishing; 2023.
- Lu M, Chen C, Lan Y, Xiao J, Li R, Huang J, et al. Capsaicin-the major bioactive ingredient of chili peppers:
bio-efficacy and delivery systems. Food Funct. 2020;11(4):2848-60.
- Demirbilek S, Ersoy MO, Demirbilek S, Karaman A, Gürbüz N, Bayraktar N, et al. Small-dose capsaicin
reduces systemic inflammatory responses in septic rats. Anesth Analg. 2004;99(5):1501-7.
- Li J, Wang H, Zhang L, An N, Ni W, Gao Q, et al. Capsaicin affects macrophage anti-inflammatory activity via
the MAPK and NF-κB signaling pathways. Int J Vitam Nutr Res. 2023;93(4):289-97.
- Şen LS, Özdemir Kumral ZN, Memi G, Ercan F, Yeğen BC, Yeğen C. The gastroprotective effect of obestatin
on indomethacin-induced acute ulcer is mediated by a vagovagal mechanism. Physiol Int. 2020;107(2):243-
55.
- Arabacı Tamer S, Akbulut S, Peker Eyüboğlu İ, Erdoğan Ö, Çevik Ö, Akkiprik M, et al. Peripheral
administration of Neuropeptide-W protects against stress-induced gastric injury in rats. Life Sci.
2022;310:121087.
- Magierowska K, Wojcik D, Chmura A, Bakalarz D, Wierdak M, Kwiecien S, et al. Alterations in gastric mucosal
expression of calcitonin gene-related peptides, vanilloid receptors, and heme oxygenase-1 mediate
gastroprotective action of carbon monoxide against ethanol-induced gastric mucosal lesions. Int J Mol Sci.
2018;19(10):2960.
- Esplugues JV, Whittle BJ. Gastric damage following local intra-arterial administration of reactive oxygen
metabolites in the rat. Br J Pharmacol. 1989;97(4):1085-92.
- Kim HJ, Kim SY, Shin SP, Yang YJ, Bang CS, Baik GH, et al. Immunological measurement of
aspartate/alanine aminotransferase in predicting liver fibrosis and inflammation. Korean J Intern Med.
2020;35(2):320-30.
- Paulis G, Paulis A, De Giorgio G, Quattrocchi S. Measurement of Oxidative Stress Index (OSI) in Penile
Corpora Cavernosa and Peripheral Blood of Peyronie's Disease Patients: A Report of 49 Cases. Metabolites.
2024;14(1):55.
- Inan M, Uz YH, Kizilay G, Topcu-Tarladacalisir Y, Sapmaz-Metin M, Akpolat M, et al. Protective effect of
sildenafil on liver injury induced by intestinal ischemia/reperfusion. J Pediatr Surg. 2013;48(8):1707-15.
- Ahmed ZA. Gastroprotective effect of quercetin and misoprostol in ethanol-induced gastric ulcer in rats. Turk J
Gastroenterol. 2024;35(11):822-30.
- Wang XY, Hao M, Li YP, Zhang J, Xu QS, Yang F, et al. Structural characteristics of a purified Evodiae
fructus polysaccharide and its gastroprotection and relevant mechanism against alcohol-induced gastric
lesions in rats. Int J Biol Macromol. 2024;281(Pt 3):136410.
- Xu Y, Lin L, Zheng H, Xu S, Hong X, Cai T, et al. Protective effect of Amauroderma rugosum ethanol extract
and its primary bioactive compound, ergosterol, against acute gastric ulcers based on LXR-mediated gastric
mucus secretions. Phytomedicine. 2024;123:155236.
- Venturini CL, Damazo AS, Silva MJD, Muller JAI, Oliveira DM, Figueiredo FF, et al. Antiulcer activity and
mechanism of action of the hydroethanolic extract of leaves of Terminalia argentea Mart. in different in vivo
and in vitro experimental models. J Ethnopharmacol. 2024;318(Pt B):116972.
- Krishnamurthy HK, Pereira M, Rajavelu I, Jayaraman V, Krishna K, Wang T, et al. Oxidative stress:
fundamentals and advances in quantification techniques. Front Chem. 2024;12:1470458.
- Guo C, Ding P, Xie C, Ye C, Ye M, Pan C, et al. Potential application of the oxidative nucleic acid damage
biomarkers in detection of diseases. Oncotarget. 2017;8(43):75767-77.
- Sarıyer ET, Baş M, Çolak H, Özkan Yenal N, Unay Demirel Ö, Yüksel M. Comparison of dietary
supplementation with krill oil, fish oil, and astaxanthin on an experimental ethanol-induced gastric ulcer model:
A biochemical and histological study. Nutrients. 2024;16(20):3426.
- Zhao Z, Wei G, Wang L, Jiang Y, Zhang X, Fang L, et al. Pretreatment with Dan-Shen-Yin granules alleviates
ethanol-induced gastric mucosal damage in rats by inhibiting oxidative stress and apoptosis via Akt/Nrf2
signaling pathway. Phytomedicine. 2024;132:155866.
- Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative stress as a major cause of age-
related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov. 2009;3(1):73-80.
- Piechota-Polanczyk A, Fichna J. Review article: the role of oxidative stress in pathogenesis and treatment of
inflammatory bowel diseases. Naunyn Schmiedebergs Arch Pharmacol. 2014;387(7):605-20.
- Hsuan CF, Tsai IT, Fang LW, Chang TH, Chen YL, Houng HY, et al. Aibika flower flavonoid extract exhibits
antiulcer activity in a murine model of ethanol-induced acute gastric injury. J Med Food. 2024;27(7):615-26.
- Fan P, Xie S, Zhang Z, Yuan Q, He J, Zhang J, et al. Dendrobium officinale flos water extract ameliorates
ethanol-induced acute gastric mucosal injury via inhibiting oxidative stress and inflammation. J Sci Food
Agric. 2024;104(14):8593-603.
- Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species.
Biochim Biophys Acta. 2016;1863(12):2977-92.
- Yoshida K, Miki Y. The cell death machinery governed by the p53 tumor suppressor in response to DNA
damage. Cancer Sci. 2010;101(4):831-5.
- Russo M, Mupo A, Spagnuolo C, Russo GL. Exploring death receptor pathways as selective targets in cancer
therapy. Biochem Pharmacol. 2010;80(5):674-82.
- Orrenius S, Gogvadze V, Zhivotovsky B. Calcium and mitochondria in the regulation of cell death. Biochem
Biophys Res Commun. 2015;460(1):72-81.
- Alamoudi JA, El-Masry TA, El-Nagar MMF, El Zahaby EI, Elmorshedy KE, Gaballa MMS, et al.
Chitosan/hesperidin nanoparticles formulation: a promising approach against ethanol-induced gastric ulcers
via Sirt1/FOXO1/PGC-1α/HO-1 pathway. Front Pharmacol. 2024;15:1433793.
- Lin K, Wang Z, Wang E, Zhang X, Liu X, Feng F, et al. Targeting TRPV1 signaling: Galangin improves
ethanol-induced gastric mucosal injury. J Ethnopharmacol. 2024;335:118605.
Protective effect of peroral capsaicin administration in ethanol-induced gastric ulcer model in rats.
Yıl 2025,
Cilt: 64 Sayı: 1, 98 - 106, 12.03.2025
Mete Keçeci
,
Meryem Akpolat Ferah
,
Habib Khoshvaghti
,
Osman Cengil
Öz
Aim: Capsaicin is a compound that possesses antioxidants and anti-inflammatory properties, and it is found in almost all bitter fruits. The objective of our study was to investigate the protective effect of capsaicin in an ethanolic ulcer model.
Materials and Methods: The male Wistar albino rats were divided into four groups, comprising a control group and three experimental groups (n=8). The control group (C) administered a single dose of distilled water subcutaneously. The Capsaicin (CAP) group was administered a single dose of 1 mg/kg CAP via gavage. The ulcer group administered a single dose of 1ml absolute alcohol via gavage, 30 minutes following the administration of a single dose of distilled water via gavage. The U+CAP group administered 1ml of absolute alcohol 30 minutes following the administration of 1 mg/kg CAP. Macroscopic and microscopic ulcer scores, as well as mucosal barrier integrity, were evaluated in the gastric tissues that had been removed. The levels of total oxidant status (TOS) and total antioxidant status (TAS) were determined in the tissue samples, and an oxidative stress index (OSI) was calculated. Results: In comparison to the U group, the macroscopic and microscopic mucosal lesions, TOS, OSI levels and IL-1, TNF-α, NFκB and Caspase 3 expressions were found to be decreased in the U+CAP group, while TAS levels were observed to be increased.
Conclusion: The results of the study demonstrated that capsaicin protects mucosal integrity through its antioxidant, anti-inflammatory and anti-apoptotic properties in the ethanol-induced gastric ulcer model.
Etik Beyan
The study was conducted in accordance with the guidelines set forth in the Guide for the Care and Use of Laboratory Animals, published by the US Public Health Service. Prior to the commencement of the study, approval was obtained from the Institutional Animal Ethics Committee of Bülent Ecevit University (Zonguldak, Turkey; 2020-06-27/02).
Destekleyen Kurum
This study was supported by Zonguldak Bülent Ecevit University Scientific Research Projects Coordination (2020-98210206-01).
Proje Numarası
2020-98210206-01
Kaynakça
- Lin KJ, García Rodríguez LA, Hernández-Díaz S. Systematic review of peptic ulcer disease incidence rates:
do studies without validation provide reliable estimates? Pharmacoepidemiol Drug Saf. 2011;20(7):718-28.
- Del Valle J. Chapter 324: Peptic Ulcer Disease and Related Disorders. In: Loscalzo J, Fauci A, Kasper D,
Hauser S, Longo D, Jameson J, editors. Harrisons Principles of Internal Medicine, 21e. McGraw Hill; 2022.
- Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, et al. Smoking, alcohol consumption, and 24
gastrointestinal diseases: Mendelian randomization analysis. eLife. 2023;12:e84051.
- Zhou D, Yang Q, Tian T, Chang Y, Li Y, Duan LR, et al. Gastroprotective effect of gallic acid against ethanol-
induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role. Biomed
Pharmacother. 2020;126:110075.
- Orona-Ortiz A, Velázquez-Moyado JA, Pineda-Peña EA, Balderas-López JL, Tavares Carvalho JC, Navarrete
A. Effect of the proportion of curcuminoids on the gastroprotective action of Curcuma longa L. in rats. Nat
Prod Res. 2021;35(11):1903-8.
- Chang A, Rosani A, Quick J. Capsaicin. In: StatPearls. StatPearls Publishing; 2023.
- Lu M, Chen C, Lan Y, Xiao J, Li R, Huang J, et al. Capsaicin-the major bioactive ingredient of chili peppers:
bio-efficacy and delivery systems. Food Funct. 2020;11(4):2848-60.
- Demirbilek S, Ersoy MO, Demirbilek S, Karaman A, Gürbüz N, Bayraktar N, et al. Small-dose capsaicin
reduces systemic inflammatory responses in septic rats. Anesth Analg. 2004;99(5):1501-7.
- Li J, Wang H, Zhang L, An N, Ni W, Gao Q, et al. Capsaicin affects macrophage anti-inflammatory activity via
the MAPK and NF-κB signaling pathways. Int J Vitam Nutr Res. 2023;93(4):289-97.
- Şen LS, Özdemir Kumral ZN, Memi G, Ercan F, Yeğen BC, Yeğen C. The gastroprotective effect of obestatin
on indomethacin-induced acute ulcer is mediated by a vagovagal mechanism. Physiol Int. 2020;107(2):243-
55.
- Arabacı Tamer S, Akbulut S, Peker Eyüboğlu İ, Erdoğan Ö, Çevik Ö, Akkiprik M, et al. Peripheral
administration of Neuropeptide-W protects against stress-induced gastric injury in rats. Life Sci.
2022;310:121087.
- Magierowska K, Wojcik D, Chmura A, Bakalarz D, Wierdak M, Kwiecien S, et al. Alterations in gastric mucosal
expression of calcitonin gene-related peptides, vanilloid receptors, and heme oxygenase-1 mediate
gastroprotective action of carbon monoxide against ethanol-induced gastric mucosal lesions. Int J Mol Sci.
2018;19(10):2960.
- Esplugues JV, Whittle BJ. Gastric damage following local intra-arterial administration of reactive oxygen
metabolites in the rat. Br J Pharmacol. 1989;97(4):1085-92.
- Kim HJ, Kim SY, Shin SP, Yang YJ, Bang CS, Baik GH, et al. Immunological measurement of
aspartate/alanine aminotransferase in predicting liver fibrosis and inflammation. Korean J Intern Med.
2020;35(2):320-30.
- Paulis G, Paulis A, De Giorgio G, Quattrocchi S. Measurement of Oxidative Stress Index (OSI) in Penile
Corpora Cavernosa and Peripheral Blood of Peyronie's Disease Patients: A Report of 49 Cases. Metabolites.
2024;14(1):55.
- Inan M, Uz YH, Kizilay G, Topcu-Tarladacalisir Y, Sapmaz-Metin M, Akpolat M, et al. Protective effect of
sildenafil on liver injury induced by intestinal ischemia/reperfusion. J Pediatr Surg. 2013;48(8):1707-15.
- Ahmed ZA. Gastroprotective effect of quercetin and misoprostol in ethanol-induced gastric ulcer in rats. Turk J
Gastroenterol. 2024;35(11):822-30.
- Wang XY, Hao M, Li YP, Zhang J, Xu QS, Yang F, et al. Structural characteristics of a purified Evodiae
fructus polysaccharide and its gastroprotection and relevant mechanism against alcohol-induced gastric
lesions in rats. Int J Biol Macromol. 2024;281(Pt 3):136410.
- Xu Y, Lin L, Zheng H, Xu S, Hong X, Cai T, et al. Protective effect of Amauroderma rugosum ethanol extract
and its primary bioactive compound, ergosterol, against acute gastric ulcers based on LXR-mediated gastric
mucus secretions. Phytomedicine. 2024;123:155236.
- Venturini CL, Damazo AS, Silva MJD, Muller JAI, Oliveira DM, Figueiredo FF, et al. Antiulcer activity and
mechanism of action of the hydroethanolic extract of leaves of Terminalia argentea Mart. in different in vivo
and in vitro experimental models. J Ethnopharmacol. 2024;318(Pt B):116972.
- Krishnamurthy HK, Pereira M, Rajavelu I, Jayaraman V, Krishna K, Wang T, et al. Oxidative stress:
fundamentals and advances in quantification techniques. Front Chem. 2024;12:1470458.
- Guo C, Ding P, Xie C, Ye C, Ye M, Pan C, et al. Potential application of the oxidative nucleic acid damage
biomarkers in detection of diseases. Oncotarget. 2017;8(43):75767-77.
- Sarıyer ET, Baş M, Çolak H, Özkan Yenal N, Unay Demirel Ö, Yüksel M. Comparison of dietary
supplementation with krill oil, fish oil, and astaxanthin on an experimental ethanol-induced gastric ulcer model:
A biochemical and histological study. Nutrients. 2024;16(20):3426.
- Zhao Z, Wei G, Wang L, Jiang Y, Zhang X, Fang L, et al. Pretreatment with Dan-Shen-Yin granules alleviates
ethanol-induced gastric mucosal damage in rats by inhibiting oxidative stress and apoptosis via Akt/Nrf2
signaling pathway. Phytomedicine. 2024;132:155866.
- Khansari N, Shakiba Y, Mahmoudi M. Chronic inflammation and oxidative stress as a major cause of age-
related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov. 2009;3(1):73-80.
- Piechota-Polanczyk A, Fichna J. Review article: the role of oxidative stress in pathogenesis and treatment of
inflammatory bowel diseases. Naunyn Schmiedebergs Arch Pharmacol. 2014;387(7):605-20.
- Hsuan CF, Tsai IT, Fang LW, Chang TH, Chen YL, Houng HY, et al. Aibika flower flavonoid extract exhibits
antiulcer activity in a murine model of ethanol-induced acute gastric injury. J Med Food. 2024;27(7):615-26.
- Fan P, Xie S, Zhang Z, Yuan Q, He J, Zhang J, et al. Dendrobium officinale flos water extract ameliorates
ethanol-induced acute gastric mucosal injury via inhibiting oxidative stress and inflammation. J Sci Food
Agric. 2024;104(14):8593-603.
- Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species.
Biochim Biophys Acta. 2016;1863(12):2977-92.
- Yoshida K, Miki Y. The cell death machinery governed by the p53 tumor suppressor in response to DNA
damage. Cancer Sci. 2010;101(4):831-5.
- Russo M, Mupo A, Spagnuolo C, Russo GL. Exploring death receptor pathways as selective targets in cancer
therapy. Biochem Pharmacol. 2010;80(5):674-82.
- Orrenius S, Gogvadze V, Zhivotovsky B. Calcium and mitochondria in the regulation of cell death. Biochem
Biophys Res Commun. 2015;460(1):72-81.
- Alamoudi JA, El-Masry TA, El-Nagar MMF, El Zahaby EI, Elmorshedy KE, Gaballa MMS, et al.
Chitosan/hesperidin nanoparticles formulation: a promising approach against ethanol-induced gastric ulcers
via Sirt1/FOXO1/PGC-1α/HO-1 pathway. Front Pharmacol. 2024;15:1433793.
- Lin K, Wang Z, Wang E, Zhang X, Liu X, Feng F, et al. Targeting TRPV1 signaling: Galangin improves
ethanol-induced gastric mucosal injury. J Ethnopharmacol. 2024;335:118605.