Melatonin protects against ischemia/reperfusion-induced oxidative damage to mitochondria in fetal rat brain.
We investigated the effects of melatonin on ischemia/reperfusion-induced oxidative damage to mitochondria in fetal rat brain. The utero-ovarian arteries were occluded bilaterally for 20 min in female Wistar rats on day 19 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring 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 occlusion. We measured the respiratory control index (RCI) and the adenosine 5-diphosphate (ADP)/oxygen ratio as indicators of mitochondrial respiratory activity, as well as the concentration of thiobarbituric acid-reactive substances (TBARS) in the mitochondria of fetal brain. Ischemia/reperfusion significantly elevated the concentration of TBARS and significantly reduced the RCI as well as the ADP/oxygen ratio. Melatonin treatment reversed the ischemia/reperfusion-induced reductions in the RCI (2.29 +/- 0.06-2.64 +/- 0.09, P < 0.05) and in the ADP/oxygen ratio (1.48 +/- 0.03-1.57 +/- 0.02, P < 0.05), and also reduced the elevation in concentration of TBARS (11.00 +/- 0.34-7.57 +/- 0.74 nM/mg protein, P < 0.01), resulting in values similar to those in untreated, sham-ischemic animals. The results indicate that administration of melatonin to pregnant rats may prevent ischemia/reperfusion-induced oxidative mitochondrial damage in fetal rat brain.
Wakatsuki
A
A
Department of Obstetrics and Gynecology, Kochi Medical School, Japan. wakatuki@kochi-ms.ac.jp
Okatani
Y
Y
Shinohara
K
K
Ikenoue
N
N
Fukaya
T
T
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D000244:Adenosine Diphosphate; D008550:Melatonin