Anti-atherogenic effect of BHB-TZD having inhibitory activities on cyclooxygenase and 5-lipoxygenase in hyperlipidemic mice
- Authors
- Choi, Jae-Hoon; Jeon, Hyung Jun; Park, Jong-Gil; Sonn, Seong Keun; Lee, Mi-Ran; Lee, Mi-Ni; You, Hye Jin; Kim, Geun-Young; Kim, Jae-Hong; Lee, Mun Han; Kwon, Oh-Seung; Nam, Ki-Hoan; Kim, Hyoung-Chin; Jeong, Tae-Sook; Lee, Woo Song; Oh, Goo Taeg
- Issue Date
- Sep-2010
- Publisher
- ELSEVIER IRELAND LTD
- Keywords
- BHB-TZD; Atherosclerosis; Cyclooxygenase; 5-Lipoxygenase
- Citation
- ATHEROSCLEROSIS, v.212, no.1, pp.146 - 152
- Indexed
- SCIE
SCOPUS
- Journal Title
- ATHEROSCLEROSIS
- Volume
- 212
- Number
- 1
- Start Page
- 146
- End Page
- 152
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/115730
- DOI
- 10.1016/j.atherosclerosis.2010.05.003
- ISSN
- 0021-9150
- Abstract
- Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX), which play pivotal roles in atherogenesis, have been reported to be involved in plaque stability. Licofelone, a dual COX and 5-LOX inhibitor, has been reported to possess anti-atherogenic effect in rabbit atherosclerosis model. We therefore investigated the anti-atherogenic effect of BHB-TZD [5-(3,5-di-tert-butyl-4-hydroxybenzylidene)thiazolidin-2,4-dione], a dual COX and 5-LOX inhibitor, in low density lipoprotein receptor null (LDLR-/-) mice. Fifteen LDLR-/- mice were fed a western diet (control group), whereas 15 were fed a western diet plus 0.1% (w/w) BHB-TZD (BHB-TZD group). After 8 weeks, the BHB-TZD group had markedly lower serum levels of leukotriene B4 and prostaglandin E2 than the control group. Interestingly, BHB-TZD treatment also reduced plasma triglyceride level without significant changes in total cholesterol and HDL levels. Compared with control mice, BHB-TZD fed mice had 52% fewer fatty streak lesions in the aortic sinus, as well as fewer initial lesions in the aortic arch. Macrophage infiltration into the lesions was 40% lower, and collagen and smooth muscle cells were increased by 102% and 96%, respectively, in the BHB-TZD group compared with the control group. In addition, aortic expression of proatherogenic molecules including TNF-alpha, IL-1 beta, IL-6, MCP-1 and VCAM-1, was lower in the BHB-TZD group than the control group. BHB-TZD treatment also reduced MMP-2 and MMP-9 expressions in aorta. In conclusion, BHB-TZD effectively attenuated atherosclerosis in mouse model, suggesting its therapeutic potential for atherosclerosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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