Melatonin protects against age-related DNA damage in the brains of female senescence-accelerated mice.
We investigated whether melatonin reduces the age-related susceptibility of brain to oxidative DNA damage. Brain tissues and blood samples were obtained in the middle of dark period of the daily light:dark cycle from female senescence-accelerated mice (SAM-P/6) at ages 4, 8, and 12 months. Serum melatonin concentrations and the contents of deoxyguanosine (dG) and 8-hydroxydeoxyguanosine (8-OHdG) in DNA extracted from these brain homogenates were measured by high-performance liquid chromatography. Contents of 8-OHdG showed a significant age-related increase (P < 0.001) while that of dG did not. The 8-OHdG:dG ratio also exhibited a significant age-related increase (P < 0.001). Serum melatonin concentration decreased markedly between 8 (159.7 +/- 4.5 pg/mL) and 12 (46.8 + 4.5 pg/mL) months of age (P < 0.0001). Oral melatonin administration (2 microg/mL in water) starting at 8 months of age, which produced a significant increase in serum melatonin concentration at 12 months (187.6 +/- 18.3 pg/mL) compared with untreated animals (P < 0.0001) also resulted in significant decreases in brain 8-OHdG contents and 8-OHdG:dG ratios. These results indicate that administration of a physiologic dose of melatonin to SAM-P 6 mice may prevent the age-related oxidative DNA damage in the brain.
Morioka
N
N
Department of Obstetrics and Gynecology, Kochi Medical School, Japan.
Okatani
Y
Y
Wakatsuki
A
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002940:Circadian Rhythm; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D008550:Melatonin / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010870:Pineal Gland / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D008550:Melatonin