Melatonin protects against ischemia and reperfusion-induced oxidative lipid and DNA damage in fetal rat brain.
To investigate whether melatonin reduces the susceptibility of the fetal rat brain to oxidative damage of lipids and DNA, we created a model of fetal ischemia/reperfusion using rats at day 19 of pregnancy. Fetal ischemia was induced by bilateral occlusion of the utero-ovarian artery for 20 min. Reperfusion was achieved by releasing the occlusion and restoring the circulation for 30 min. A sham operation was performed in control rats. Melatonin (10 mg/kg) or vehicle was injected intraperitoneally 60 min prior to the occlusion. We measured the concentration of thiobarbituric acid reactive substances (TBARS) in fetal brain homogenates, as well as levels of deoxyguanosine (dG) and 8-hydroxydeoxyguanosine (8-OHdG) in DNA extracted from those homogenates. Ischemia for 20 min did not significantly alter the levels of dG, 8-OHdG, and TBARS. Subsequent reperfusion, however, led to a significant reduction in the dG level (P < 0.05) and to significant increases in the levels of 8-OHdG (P < 0.05) and TBARS (P < 0.05), and in the 8-OHdG/dG ratio (P < 0.005). Melatonin administration prior to ischemia significantly reduced the ischemia/reperfusion-induced increases in the levels of 8-OHdG (14.33 +/- 6.52-5.15 +/- 3.28 pmol/mg of DNA, P < 0.001) and TBARS (11.61 +/- 3.85-4.73 +/- 3.80 nmol/mg of protein, P < 0.001) as well as in the 8-OHdG/dG ratio (7.19 +/- 2.49-1.61 +/- 0.98, P < 0.001). Furthermore, melatonin significantly increased the dG level (210.19 +/- 49.02-299.33 +/- 65.08 nmol/mg of DNA, P < 0.05). Results indicate that melatonin administration to the pregnant rat may prevent the ischemia/reperfusion-induced oxidative lipid and DNA damage in fetal rat brain.
Wakatsuki
A
A
Department of Obstetrics and Gynecology, Kochi Medical School, Japan.
Okatani
Y
Y
Izumiya
C
C
Ikenoue
N
N
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D017392:Thiobarbituric Acid Reactive Substances; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D008550:Melatonin