title: Effect of tocopheryl phosphate on key biomarkers of inflammation: Implication in the reduction of atherosclerosis progression in a hypercholesterolaemic rabbit model.
abstract: 1. Many studies have evaluated the effectiveness of alpha-tocopherol (vitamin E) in the development and progression of cardiovascular diseases, with conflicting results reported on the protective effect of this anti-oxidant. 2. The present study examined the effectiveness of a novel tocopheryl phosphate mixture (TPm) compared with that of alpha-tocopherol (TA) on key pro-inflammatory markers involved in atherogenesis, including interleukin (IL)-1beta, IL-6, IL-8, plasminogen activator inhibitor-1, tumour necrosis factor-alpha and C-reactive protein (CRP), as well as vascular function and lesion development in rabbits fed a 2% cholesterol diet. 3. Treatment with TPm, incorporated into the rabbit food at four doses ranging from 60 to 360 mg/kg chow, resulted in a significant reduction in plasma levels of all pro-inflammatory cytokines and biomarkers that appeared to be somewhat dose dependent. Conversely, treatment with TA, at a dose equivalent to the highest dose of TPm used, only decreased plasma levels of CRP, IL-6 and IL-8. Both TPm and TA treatment significantly improved vascular function to a similar extent, although TPm was more effective in reducing lesion development. 4. The reduction in these key pro-inflammatory markers appears to follow the improvement in the atherogenic state of the animals, indicating that the anti-inflammatory properties of TPm may be potentially beneficial in inflammatory disease states.
authors.affiliation: Phosphagenics Limited, Monash University, Melbourne, Vic., Australia. Email: rlibinaki@phosphagenics.com
authors.forename: Roksan
authors.initials: R
authors.lastname: Libinaki
authors.forename: Sonja
authors.initials: S
authors.lastname: Tesanovic
authors.forename: Aileen
authors.initials: A
authors.lastname: Heal
authors.forename: Billie
authors.initials: B
authors.lastname: Nikolovski
authors.forename: Antony
authors.initials: A
authors.lastname: Vinh
authors.forename: Robert E
authors.initials: RE
authors.lastname: Widdop
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Gaspari
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.forename: Esra
authors.initials: E
authors.lastname: Ogru
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000473:pathology; D066298:In Vitro Techniques; D008055:Lipids / Q000097:blood; D008297:Male; D011817:Rabbits; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D008055:Lipids; C012552:alpha-tocopherol phosphate; D024502:alpha-Tocopherol