Docosahexaenoic acid supplementation-increased oxidative damage in bone marrow DNA in aged rats and its relation to antioxidant vitamins.
We compared the influence of docosahexaenoic acid (DHA) supplementation on oxidative DNA damage in bone marrow between young and aged rats. As a marker of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG) in DNA was analyzed. Young (5-week-old) and aged (100-week-old) female Wistar rats were given DHA (300mg/kg body weight/day) or vehicle (control) orally for 12 weeks. The 8-OHdG in the bone marrow in the aged DHA group was significantly higher than that in the other groups. Vitamin E concentrations, however, did not differ among the groups regardless of the DHA supplementation. Vitamin C (ascorbic acid) concentrations in the aged control group were approximately 1/2 those in the young control group. The concentrations of vitamin C tended to be higher in the young DHA group and lower in the aged DHA group when compared to their respective control groups. Changes in the concentrations of vitamin C and vitamin E in plasma were similar to those in the bone marrow. The activity of hepatic l-gulono- gamma -lactone oxidase, an enzyme responsible for vitamin C synthesis, corresponded well to the concentrations of vitamin C in the bone marrow and the plasma. These results suggest that in aged rats, but not young rats, excess supplementation of DHA induces oxidative DNA damage in bone marrow and that the decrease in vitamin C synthesis in aged rats is involved in the mechanisms of DNA damage.
Umegaki
K
K
The National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan. umegaki@nih.go.jp
Hashimoto
M
M
Yamasaki
H
H
Fujii
Y
Y
Yoshimura
M
M
Sugisawa
A
A
Shinozuka
K
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D001853:Bone Marrow / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism*; D019587:Dietary Supplements / Q000009:adverse effects*; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D005260:Female; D050544:L-Gulonolactone Oxidase; D008054:Lipid Peroxides / Q000032:analysis / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013401:Sugar Alcohol Dehydrogenases / Q000737:chemistry / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides / Q000032:analysis / Q000097:blood; D014810:Vitamin E / Q000032:analysis / Q000097:blood / Q000494:pharmacology*
D000975:Antioxidants; D005227:Fatty Acids; D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D014810:Vitamin E; D004281:Docosahexaenoic Acids; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D002784:Cholesterol; D013401:Sugar Alcohol Dehydrogenases; D050544:L-Gulonolactone Oxidase; D003849:Deoxyguanosine; D001205:Ascorbic Acid