Inhibitory effect of a novel water-soluble vitamin E derivative on atherosclerosis in rabbits.
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.
Yoshida
Norimasa
N
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. nyoshida@koto.kpu-m.ac.jp
Murase
Hironobu
H
Kunieda
Tsutomu
T
Toyokuni
Shinya
S
Tanaka
Tomoyuki
T
Terao
Junji
J
Naito
Yuji
Y
Tanigawa
Toru
T
Yoshikawa
Toshikazu
T
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*
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