Chronic daily administration of ethyl docosahexaenoate protects against gerbil brain ischemic damage through reduction of arachidonic acid liberation and accumulation.
Recently, we reported that dietary ethyl docosahexaenoate (Et-DHA) intake decreases the level of membrane arachidonic acid (AA), which reduces the generation of AA metabolites in ischemic gerbil brain. As an extended study, we further investigated the influence of the chronic administration of Et-DHA on free AA levels after ischemia. In addition, Na,K-ATPase activity, cation content, cerebral edema and brain damage were also evaluated. Weanling male gerbils were orally pretreated with either Et-DHA (200 mg/kg) or vehicle, once a day for 10 weeks, and subjected to transient forebrain ischemia by bilateral common carotid occlusion for 30 min. Time-course analyses revealed that pretreatment with Et-DHA, compared with pretreatment with the vehicle, significantly decreased the brain's free AA levels during ischemia (5, 15 and 30 min) and after reperfusion (5, 10, 15 and 30 min), and attenuated the decline of Na,K-ATPase activity at examined time points. Pretreatment with Et-DHA significantly prevented an increase in Na(+) concentration and a decrease in K(+) concentration after 24 h of reperfusion, which resulted in lower cerebral water content. Reduced brain infarct volume and low animal mortality were also observed in Et-DHA-treated animals. These data suggest that the reduction of ischemia-induced AA liberation and accumulation by Et-DHA pretreatment may be attributable to (a) protection against the decline of Na,K-ATPase activity, (b) postischemic cerebral edema and brain damage and (c) animal mortality.
Cao
Dehua
D
Department of Biology, School of Life Sciences, Nanjing University, Jiangsu, Nanjing 210093, PR China.
Yang
Bingya
B
Hou
Lijuan
L
Xu
Jun
J
Xue
Renhao
R
Sun
Liping
L
Zhou
Chen
C
Liu
Zhili
Z
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000517:prevention & control; D002545:Brain Ischemia / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D005849:Gerbillinae; D008297:Male; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D015996:Survival Rate
D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium