Intraamniotic ethyl docosahexaenoate administration protects fetal rat brain from ischemic stress.
Studies were conducted on the prenatal rat given a single intraamniotic injection of ethyl docosahexaenoate (Et-DHA; 9.6-12 mmol per fetus) or subjected to an n-3 fatty acid-deficient diet to assess the role of docosahexaenoate on oxidative stress during episodes of ischemia. A time-dependent decrease in the ability of brain slices from animals treated with Et-DHA to produce thiobarbituric acid-reactive substance (TBARS), most pronounced after 1 day (from 58.1 +/- 4.22 to 15.9 +/- 1.6 nmol/mg of DNA), was noticed on stimulation with Fe2+. Brain slices from fetuses treated for 1 day with Et-DHA and those from untreated fetuses produced TBARS levels of 46.7 +/- 6.5 and 114.8 +/- 10.8 nmol/mg of DNA, respectively, after a 20-min occlusion of the fetal-maternal circulation at embryonic day 20, suggesting a protective effect of Et-DHA. The protective effect of a single dose of Et-DHA in utero remained high up to 3 days after injection (p < 0.001) and was long-lasting, yet not significant, up to 3 days following birth. In agreement with a reduction in TBARS production by slices, the endogenous levels of TBARS in brains of Et-DHA-treated animals were lower than in the controls. Et-DHA-injected fetuses exhibited significantly higher levels of esterified DHA than the noninjected controls. n-3-deficient diet given to dams for 2 weeks before birth did not affect the levels of TBARS production in control fetal brain slices but abolished the increase caused by ischemia. Et-DHA administration for 24 h to n-3-deficient fetuses reduced the amount of TBARS produced by the fetal brain slices from 49.1 +/- 8.5 to 31.7 +/- 4.1 nmol/mg of DNA. A protective effect from oxidative damage after postischemic oxidative stress in fetal brain following DHA supplements is suggested, whereas the effect of n-3 fatty acid deficiency in this regard is more ambiguous.
Glozman
S
S
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Green
P
P
Yavin
E
E
D000650:Amnion; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D018752:Diet, Fat-Restricted; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000098:blood supply / Q000378:metabolism*; D007267:Injections; D007511:Ischemia / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D004281:Docosahexaenoic Acids; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester