The production of hydroxyl radicals in the fetal lamb brain resulting from occlusion of the umbilical circulation and the transplacental effect of MCI-186 to inhibit hydroxyl radical production.
The present study evaluated hydroxyl radical production in fetal lamb brain during and after umbilical cord occlusion and examined the effects of injecting MCI-186 (3-metyl-1-phenyl-2-pyrazolin-5-one; Edaravone), a hydroxyl radical scavenger, into the maternal circulation. In 11 chronically instrumented lambs, intermittent total umbilical cord occlusions 1 min out of every 3 min for 1 h and 10-min persistent total umbilical cord occlusion were performed with brain microdialysis using 5 mM of sodium salicylate. In the remaining four lambs, 60 mg of MCI-186 was administered into the maternal circulation from shortly before the end of 10-min persistent total umbilical cord occlusion. Concentrations of 2,3-dihydroxy-benzoic acid (2,3-DHBA), produced by hydroxyl radical reactions with sodium salicylate, were measured in perfusate by HPLC. Concentration of 2,3-DHBA in perfusate was 23.05 +/- 10.95 nM before umbilical cord occlusion. Levels of 2,3-DHBA tended to increase slightly during and after intermittent umbilical cord occlusion, and were significantly increased by the end of 10-min occlusion (40.06 +/- 21.36 nM) and after occlusion (93.74 +/- 29.17 nM). Infusion of MCI-186 suppressed 2,3-DHBA concentration to 29.35 +/- 14.95 nM after occlusion. Administration of MCI-186 into the maternal circulation reduces hydroxyl radical production induced by umbilical cord occlusion in the fetal lamb brain.
Nakajima
Yoshiyuki
Y
Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan. nakaj613@abeam.ocn.ne.jp
Masaoka
Naoki
N
Hayakawa
Yasuhito
Y
Watanabe
Masao
M
Nagaishi
Masaji
M
Sakata
Hisaei
H
Yamamoto
Tatsuo
T
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000493:pharmacokinetics*; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012039:Regional Blood Flow; D012756:Sheep / Q000196:embryology; D014470:Umbilical Cord / Q000502:physiology*
D002396:Catechols; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D000077553:Edaravone; D000983:Antipyrine