Effect of cyclooxygenase genotype and dietary fish oil on colonic eicosanoids in mice

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• 作者：Andrew P. Neilson ; Zora Djuric ; Jianwei Ren ; Yu H. Hong ; An ; a Sen ; Corey Lager ; Yan Jiang ; Shony Reuven ; William L. Smith ; Dean E. Brenner
• 关键词：AA ; arachidonic acid ; AIN ; American Institute of Nutrition ; COX ; cyclooxygenase ; DAB ; 3 ; 3&prime ; -diaminobenzidine ; DHA ; docosahexaenoic acid ; EPA ; eicosapentaenoic acid ; ESI ; electrospray ionization ; EPZ ; extent of the proliferative zone ; H/E ; hematoxylin
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：23
• 期：8
• 页码：966-976
• 全文大小：1227 K

文摘

Dietary ¦Ø3 fatty acids can modulate substrate availability for cyclooxygenases (COXs) and lipoxygenases, thus modulating downstream eicosanoid formation. This could be an alternative approach to using nonsteroidal anti-inflammatory drugs and other COX inhibitors for limiting Prostaglandin E₂ (PGE₂) synthesis in colon cancer prevention. The aims of this study were to evaluate to what extent COX- and lipoxygenase-derived products could be modulated by dietary fish oil in normal colonic mucosa and to evaluate the role of COX-1 and COX-2 in the formation of these products. Mice (wild-type, COX-1 null or COX-2 null) were fed a diet supplying a broad mixture of fatty acids present in European/American diets, supplemented with either olive oil (oleate control diet) or menhaden (fish) oil ad libitum for 9-11 weeks. Colonic eicosanoid levels were measured by liquid chromatography tandem mass spectroscopy (LC-MS/MS), and proliferation was assessed by Ki67 immunohistochemistry. For the dietary alteration of colonic arachidonic acid: eicosapentaenoic ratios resulted in large shifts in formation of COX and lipoxygenase metabolites. COX-1 knockout virtually abolished PGE₂ formation, but interestingly, 12-hydroxyeicosatetraenoic (12-HETE) acid and 15-HETE formation was increased. The large changes in eicosanoid profiles were accompanied by relatively small changes in colonic crypt proliferation, but such changes in eicosanoid formation might have greater biological impact upon carcinogen challenge. These results indicate that in normal colon, inhibition of COX-2 would have little effect on reducing PGE₂ levels.