title: Maternal treatment with alpha-phenyl-N-tert-butylnitrone attenuates secondary mitochondrial dysfunction after transient intrauterine asphyxia in the fetal rat brain.
abstract: Recirculation following 30 min of ischemia due to transient uterine artery occlusion in pregnant rats at 20 days gestation has previously been found to cause partial recovery and secondary deterioration of the cellular bioenergetic state in the fetal brain, the subsequent damage being ameliorated by a free radical spin trap agent, alpha-phenyl-N-TERT-butylnitrone (PBN). Our objective was to assess whether the secondary deterioration of the cellular bioenergetic state is due to mitochondrial dysfunction and to study whether PBN acts to prevent secondary damage to mitochondria in the fetal rat brain. Fetal neocortical tissues were sampled after 30 min of intrauterine ischemia and after 1, 2 or 4 h of recirculation. PBN or vehicle was given 1 h after recirculation. Homogenates were prepared, and ADP-stimulated, nonstimulated and uncoupled respiratory rates were measured polarographically. Ischemia was associated with a decrease in ADP-stimulated and uncoupled respiratory rates, with a marked fall in the respiratory control ratio, defined as ADP-stimulated divided by nonstimulated respiration (p < 0.01). Recirculation (1 h) brought about partial recovery, but continued reflow (2 and 4 h) was associated with a secondary deterioration of respiratory functions (p < 0.01). The secondary deterioration was prevented by PBN (p < 0.05). The results demonstrate that the secondary deterioration of the cellular bioenergetic state in ischemia-reperfusion is due to secondary mitochondrial dysfunction and that this deterioration may be induced by oxygen-derived free radicals in the immature fetal brain.
authors.affiliation: Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Taniuchi
authors.forename: Akihito
authors.initials: A
authors.lastname: Nakai
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Koshino
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Araki
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D001237:Asphyxia / Q000150:complications*; D002545:Brain Ischemia / Q000150:complications; D003250:Constriction; D003497:Cyclic N-Oxides; D005260:Female; D005315:Fetal Diseases / Q000517:prevention & control; D008431:Maternal-Fetal Exchange; D028361:Mitochondrial Diseases / Q000209:etiology / Q000517:prevention & control*; D009589:Nitrogen Oxides / Q000008:administration & dosage*; D010101:Oxygen Consumption; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000098:blood supply
chemical_list: D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D000244:Adenosine Diphosphate