Protective Effects of ACE/NEP Dual Inhibitor Omapatrilat for Indomethacin-induced Gastric Ulcer
Aim: The renin-angiotensin-aldosterone system (RAAS) plays important roles in oxidative stress and various gastroenterological mechanisms. Omapatrilat, an RAAS-acting agent, inhibits both neprilysin neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) and may therefore affect protecti...
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| Format: | Article |
| Language: | English |
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Galenos Yayincilik
2023-12-01
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| Series: | Namık Kemal Tıp Dergisi |
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http://namikkemalmedj.com/archives/archive-detail/article-preview/protective-effects-of-ace-nep-dual-nhibitor-omapat/63799
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| author | Kadir Giray ERKAYMAN Rüstem Anıl UĞAN Zeynep Berna AKSAKALLI MAĞDEN Eda YILMAZ Ayşe BOZKURT Elif ÇADIRCI |
| author_facet | Kadir Giray ERKAYMAN Rüstem Anıl UĞAN Zeynep Berna AKSAKALLI MAĞDEN Eda YILMAZ Ayşe BOZKURT Elif ÇADIRCI |
| author_sort | Kadir Giray ERKAYMAN |
| collection | DOAJ |
| description | Aim: The renin-angiotensin-aldosterone system (RAAS) plays important roles in oxidative stress and various gastroenterological mechanisms. Omapatrilat, an RAAS-acting agent, inhibits both neprilysin neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) and may therefore affect protective mechanisms against gastric ulcer. Therefore, this study examined the gastroprotective role of omapatrilat in a mouse model of gastric ulcer induced by indomethacin to reveal pharmacological and biochemical changes resulting from omapatrilat treatment. Materials and Methods: Forty-two BALB/c mice were divided into seven groups: control, 40 mg/kg omapatrilat only, 25 mg/kg indomethacin only, indomethacin and 40 mg/kg famotidine, and three groups with indomethacin and 10-40 mg/kg omapatrilat. All chemicals were administered by oral gavage in 0.5 mL of 0.9% NaCl solution at the determined doses. Stomach ulcers were induced by indomethacin in mice treated with famotidine (40 mg/kg) and omapatrilat (10-40 mg/kg). Stomach tissue samples were examined macroscopically. Oxidative stress biomarkers of malondialdehyde (MDA), glutathione (GSH), NEP and ACE levels as well as superoxide dismutase (SOD) activity were measured. Results: The best antiulcer activity was measured with 40 mg/kg omapatrilat, where the gastric damage observed in the ulcer groups was significantly reversed, and gave the most similar results to the specific famotidine treatment. In relation with the increasing omapatrilat dose, SOD activity was corrected as well as GSH and MDA levels. Also the levels of ACE and NEP decreased back towards those measured in the control group. Therefore, these macroscopic and biochemical findings indicating reversal of gastrotoxicity and gastric ulcer indications demonstrate the role of omapatrilat’s NEP and ACE inhibition in indomethacin toxicity, and its strong gastroprotective potential. Conclusion: Dual inhibition of NEP and ACE by omapatrilat may suppress oxidative stress associated with indomethacin-induced gastric ulcer. Therefore, the protective effect of omapatrilat in the treatment of ulcers may lead to the search for new treatment strategies. |
| first_indexed | 2024-03-09T01:56:31Z |
| format | Article |
| id | doaj.art-94c9c0ca3ba144d8a4820405bfd01eab |
| institution | Directory Open Access Journal |
| issn | 2587-0262 |
| language | English |
| last_indexed | 2024-03-09T01:56:31Z |
| publishDate | 2023-12-01 |
| publisher | Galenos Yayincilik |
| record_format | Article |
| series | Namık Kemal Tıp Dergisi |
| spelling | doaj.art-94c9c0ca3ba144d8a4820405bfd01eab2023-12-08T14:52:32ZengGalenos YayincilikNamık Kemal Tıp Dergisi2587-02622023-12-0111431432110.4274/nkmj.galenos.2023.8661913049054Protective Effects of ACE/NEP Dual Inhibitor Omapatrilat for Indomethacin-induced Gastric UlcerKadir Giray ERKAYMAN0Rüstem Anıl UĞAN1Zeynep Berna AKSAKALLI MAĞDEN2Eda YILMAZ3Ayşe BOZKURT4Elif ÇADIRCI5 Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Atatürk Üniversitesi Eczacılık Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Atatürk Üniversitesi Tıp Fakültesi, Tıbbi Farmakoloji Anabilim Dalı, Erzurum, Türkiye Aim: The renin-angiotensin-aldosterone system (RAAS) plays important roles in oxidative stress and various gastroenterological mechanisms. Omapatrilat, an RAAS-acting agent, inhibits both neprilysin neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) and may therefore affect protective mechanisms against gastric ulcer. Therefore, this study examined the gastroprotective role of omapatrilat in a mouse model of gastric ulcer induced by indomethacin to reveal pharmacological and biochemical changes resulting from omapatrilat treatment. Materials and Methods: Forty-two BALB/c mice were divided into seven groups: control, 40 mg/kg omapatrilat only, 25 mg/kg indomethacin only, indomethacin and 40 mg/kg famotidine, and three groups with indomethacin and 10-40 mg/kg omapatrilat. All chemicals were administered by oral gavage in 0.5 mL of 0.9% NaCl solution at the determined doses. Stomach ulcers were induced by indomethacin in mice treated with famotidine (40 mg/kg) and omapatrilat (10-40 mg/kg). Stomach tissue samples were examined macroscopically. Oxidative stress biomarkers of malondialdehyde (MDA), glutathione (GSH), NEP and ACE levels as well as superoxide dismutase (SOD) activity were measured. Results: The best antiulcer activity was measured with 40 mg/kg omapatrilat, where the gastric damage observed in the ulcer groups was significantly reversed, and gave the most similar results to the specific famotidine treatment. In relation with the increasing omapatrilat dose, SOD activity was corrected as well as GSH and MDA levels. Also the levels of ACE and NEP decreased back towards those measured in the control group. Therefore, these macroscopic and biochemical findings indicating reversal of gastrotoxicity and gastric ulcer indications demonstrate the role of omapatrilat’s NEP and ACE inhibition in indomethacin toxicity, and its strong gastroprotective potential. Conclusion: Dual inhibition of NEP and ACE by omapatrilat may suppress oxidative stress associated with indomethacin-induced gastric ulcer. Therefore, the protective effect of omapatrilat in the treatment of ulcers may lead to the search for new treatment strategies. http://namikkemalmedj.com/archives/archive-detail/article-preview/protective-effects-of-ace-nep-dual-nhibitor-omapat/63799 gastric ulcerindomethacinneprilysinoxidative stressomapatrilat |
| spellingShingle | Kadir Giray ERKAYMAN Rüstem Anıl UĞAN Zeynep Berna AKSAKALLI MAĞDEN Eda YILMAZ Ayşe BOZKURT Elif ÇADIRCI Protective Effects of ACE/NEP Dual Inhibitor Omapatrilat for Indomethacin-induced Gastric Ulcer Namık Kemal Tıp Dergisi gastric ulcer indomethacin neprilysin oxidative stress omapatrilat |
| title | Protective Effects of ACE/NEP Dual Inhibitor Omapatrilat for Indomethacin-induced Gastric Ulcer |
| title_full | Protective Effects of ACE/NEP Dual Inhibitor Omapatrilat for Indomethacin-induced Gastric Ulcer |
| title_fullStr | Protective Effects of ACE/NEP Dual Inhibitor Omapatrilat for Indomethacin-induced Gastric Ulcer |
| title_full_unstemmed | Protective Effects of ACE/NEP Dual Inhibitor Omapatrilat for Indomethacin-induced Gastric Ulcer |
| title_short | Protective Effects of ACE/NEP Dual Inhibitor Omapatrilat for Indomethacin-induced Gastric Ulcer |
| title_sort | protective effects of ace nep dual inhibitor omapatrilat for indomethacin induced gastric ulcer |
| topic | gastric ulcer indomethacin neprilysin oxidative stress omapatrilat |
| url |
http://namikkemalmedj.com/archives/archive-detail/article-preview/protective-effects-of-ace-nep-dual-nhibitor-omapat/63799
|
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