Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development
Purpose: We previously confirmed its anti-atherosclerotic effects by pre-treatment with compound-326, a selective delta-5 desaturase (D5D) inhibitor, in Western diet-fed ApoE knockout mice. In the present study, we evaluated effects of compound-326 in ApoE knockout mice with two different protocols...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Journal of Pharmacy & Pharmaceutical Sciences |
| Online Access: | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31389 |
| _version_ | 1827166462815502336 |
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| author | Hiroki Nagase Shuichi Takagahara Yoshinori Satomi Ayumi Ando Kazuki Kubo Shota Ikeda |
| author_facet | Hiroki Nagase Shuichi Takagahara Yoshinori Satomi Ayumi Ando Kazuki Kubo Shota Ikeda |
| author_sort | Hiroki Nagase |
| collection | DOAJ |
| description | Purpose: We previously confirmed its anti-atherosclerotic effects by pre-treatment with compound-326, a selective delta-5 desaturase (D5D) inhibitor, in Western diet-fed ApoE knockout mice. In the present study, we evaluated effects of compound-326 in ApoE knockout mice with two different protocols for atherosclerosis development. Methods: In a post-treatment protocol, where the compound treatment started after 10 weeks pre-feeding of Western diet, compound-326 (1 and 3 mg/kg/day, p.o. for 12 weeks) significantly reduced the atherosclerotic lesion area in the aorta (24% reduction at 3 mg/kg/day). In another protocol using Paigen diet (containing 12.5% cholesterol and 5% sodium cholate), compound-326 (3 and 10 mg/kg/day, p.o. for 7 weeks) also significantly reduced the lesion area (36% reduction at 3 mg/kg/day). Results: In both protocols, Compound-326 significantly reduced the hepatic ratio of arachidonic acid to dihomo-γ-linolenic acid, blood inflammatory eicosanoid production and plasma soluble intercellular adhesion molecule 1 (sICAM-1) levels, similarly to the previous pre-treatment study. Conclusions: Compound-326 exerted anti-atherosclerotic effects in ApoE knockout mice with the two different protocols for atherosclerosis development further supporting D5D inhibition as a promising strategy in treating atherosclerosis. |
| first_indexed | 2024-03-12T10:36:43Z |
| format | Article |
| id | doaj.art-8609ef8b9da14aee848b87bb5cb14386 |
| institution | Directory Open Access Journal |
| issn | 1482-1826 |
| language | English |
| last_indexed | 2025-03-21T01:48:47Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmaceutical Sciences |
| spelling | doaj.art-8609ef8b9da14aee848b87bb5cb143862024-08-02T22:31:36ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262021-02-012410.18433/jpps31389Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis developmentHiroki Nagase0Shuichi Takagahara1Yoshinori Satomi2Ayumi Ando3Kazuki Kubo4Shota Ikeda5Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd. Presntly, R&D Strategy & Management Office, Research Division, SCOHIA PHARMA, Inc Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Co., LtdIntegrated Technology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., LtdIntegrated Technology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., LtdCardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Co., LtdCardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Co., LtdPurpose: We previously confirmed its anti-atherosclerotic effects by pre-treatment with compound-326, a selective delta-5 desaturase (D5D) inhibitor, in Western diet-fed ApoE knockout mice. In the present study, we evaluated effects of compound-326 in ApoE knockout mice with two different protocols for atherosclerosis development. Methods: In a post-treatment protocol, where the compound treatment started after 10 weeks pre-feeding of Western diet, compound-326 (1 and 3 mg/kg/day, p.o. for 12 weeks) significantly reduced the atherosclerotic lesion area in the aorta (24% reduction at 3 mg/kg/day). In another protocol using Paigen diet (containing 12.5% cholesterol and 5% sodium cholate), compound-326 (3 and 10 mg/kg/day, p.o. for 7 weeks) also significantly reduced the lesion area (36% reduction at 3 mg/kg/day). Results: In both protocols, Compound-326 significantly reduced the hepatic ratio of arachidonic acid to dihomo-γ-linolenic acid, blood inflammatory eicosanoid production and plasma soluble intercellular adhesion molecule 1 (sICAM-1) levels, similarly to the previous pre-treatment study. Conclusions: Compound-326 exerted anti-atherosclerotic effects in ApoE knockout mice with the two different protocols for atherosclerosis development further supporting D5D inhibition as a promising strategy in treating atherosclerosis.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31389 |
| spellingShingle | Hiroki Nagase Shuichi Takagahara Yoshinori Satomi Ayumi Ando Kazuki Kubo Shota Ikeda Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development Journal of Pharmacy & Pharmaceutical Sciences |
| title | Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development |
| title_full | Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development |
| title_fullStr | Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development |
| title_full_unstemmed | Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development |
| title_short | Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development |
| title_sort | effects of compound 326 a selective delta 5 desaturase inhibitor in apoe knockout mice with two different protocols for atherosclerosis development |
| url | https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/31389 |
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