Inhibitory effects of 2-O-octadecylascorbic acid and other vitamin C and E derivatives on the induction of enzyme-altered putative preneoplastic lesions in the livers of rats fed a choline-deficient, L-amino acid-defined diet.
Effects of a lipophilic derivative of vitamin C, 2-O-octadecylascorbic acid (CV-3611), as well as its parent L-ascorbic acid (AscA), DL-alpha-tocopherol (alpha-T) and its hydrophilic derivative, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), on the number and size of gamma-glutamyltransferase (GGT)-positive putative preneoplastic lesions were examined and compared with their influences on 8-hydroxyguanine formation in DNA and 2-thiobarbituric acid-reacting substance generation in the livers of rats fed a choline-deficient, L-amino acid-defined (CDAA) diet for 12 weeks. A total of 90 male Fischer 344 rats, 6 weeks old, were divided into 18 groups each consisting of five rats. Group 1 received the CDAA diet alone; Groups 2, 3 and 4 received the CDAA diet containing respectively 0.01, 0.05 and 0.10% CV-3611; Groups 5-7, 8-10 and 11-13 similarly received the CDAA diet containing AscA, alpha-T and Trolox, respectively, at these same low, middle and high concentrations; Group 14 received a choline-supplemented, L-amino acid-defined (CSAA) diet alone; Groups 15-18 were given the CSAA diet containing CV-3611, AscA, alpha-T and Trolox, respectively, all at the 0.10% level. While all four vitamin derivatives exerted inhibitory effects on all four parameters, in each case dose-dependently, CV-3611 demonstrated the most pronounced effects. The present results indicated that lipophilic vitamin C derivatives may be particularly effective chemopreventive agents against CDAA diet-associated, oxidative stress-related hepatocarcinogenesis via its superior antioxidative properties.
Mizumoto
Y
Y
Department of Oncological Pathology, Nara Medical University, Japan.
Nakae
D
D
Yoshiji
H
H
Andoh
N
N
Horiguchi
K
K
Endoh
T
T
Kobayashi
E
E
Tsujiuchi
T
T
Shimoji
N
N
Denda
A
A
D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002796:Choline Deficiency / Q000150:complications / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D004032:Diet; D004790:Enzyme Induction / Q000187:drug effects; D016166:Free Radical Scavengers; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D011230:Precancerous Conditions / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis* / Q000378:metabolism
D000596:Amino Acids; D016166:Free Radical Scavengers; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D004247:DNA; C061185:2-O-octadecylascorbic acid; D005723:gamma-Glutamyltransferase; D001205:Ascorbic Acid