title: Inhibitory effect of a novel water-soluble vitamin E derivative on atherosclerosis in rabbits.
abstract: A novel vitamin E derivative that is freely soluble in water, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), was evaluated for ability to inhibit development of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits or cholesterol-loaded New Zealand White rabbits. Although TMG rapidly entered the circulation blood after oral administration, the blood TMG concentration remained low, while neither TMG nor its metabolites appeared in the low-density lipoprotein (LDL) fraction. TMG did not decrease serum total cholesterol and the various lipoprotein-associated cholesterol fractions (very LDL-, or high-density lipoprotein- (HDL) cholesterol). TMG reduced the serum concentration of thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation) in cholesterol-loaded rabbits but not WHHL rabbits. Nonetheless, TMG inhibited aortic atherosclerosis as effectively as probucol in both models. Our results indicate that TMG opposes progression of atherosclerosis not only by preventing oxidation of LDL, but also by presently unknown mechanisms. Even an antioxidant with no uptake by LDL apparently can inhibit development of atherosclerosis despite a very low serum concentration.
authors.affiliation: First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. nyoshida@koto.kpu-m.ac.jp
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Hironobu
authors.initials: H
authors.lastname: Murase
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kunieda
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Junji
authors.initials: J
authors.lastname: Terao
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Toru
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001011:Aorta / Q000737:chemistry / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control*; D001219:Aspartate Aminotransferases / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D002839:Chromans / Q000008:administration & dosage / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006027:Glycosides / Q000008:administration & dosage / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008955:Models, Cardiovascular; D010084:Oxidation-Reduction / Q000187:drug effects; D011341:Probucol / Q000494:pharmacology; D011817:Rabbits; D012995:Solubility; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology*
chemical_list: C106323:2-(glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol; D000975:Antioxidants; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D002839:Chromans; D006027:Glycosides; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D011341:Probucol