Effect of dietary docosahexaenoic acid in the rat middle cerebral artery thrombosis model.
We investigated the effect of dietary docosahexaenoic acid (DHA) supplementation on the thrombolytic efficacy of recombinant tissue-type plasminogen activator (rt-PA), platelet aggregability, serum cholesterol and phospholipids. Male Wistar rats (6 weeks old) received dietary DHA supplementation (300 mg/kg per day) for 8 weeks. The rat middle cerebral artery (MCA) was occluded by a thrombus induced by photochemical reaction between rose bengal and green light which cause endothelial damage followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of photochemical reaction. The MCA blood flow was monitored using a laser Doppler flowmeter. rt-PA was administered 30 min after the middle cerebral artery had been occluded by a thrombus. This regimen produced a significant (P < 0.05) decrease in serum free-cholesterol and phospholipids levels, inhibited platelet aggregation ex-vivo induced by collagen in whole blood (P < 0.05), reduced thromboxane (TX) B2 formation (P < 0.01) in whole blood and prolonged the time for thrombotic MCA occlusion (P < 0.01) as compared with values obtained from animals on standard diet. Further, dietary DHA enhanced thrombolytic efficacy of rt-PA and reduced the size of ischaemic cerebral lesions. Our findings suggest that dietary DHA produces antithrombotic effects via metabolic conversion to non-atherogenic and non-platelet stimulant metabolites.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Toshima
Y
Y
Asai
F
F
Nakashima
M
M
D000284:Administration, Oral; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D002542:Intracranial Embolism and Thrombosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008027:Light; D008297:Male; D010743:Phospholipids / Q000097:blood; D010777:Photochemistry; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D012395:Rose Bengal / Q000528:radiation effects / Q000633:toxicity; D016037:Single-Blind Method; D015912:Thrombolytic Therapy; D013929:Thromboxane B2 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D010743:Phospholipids; D011994:Recombinant Proteins; D012395:Rose Bengal; D004281:Docosahexaenoic Acids; D013929:Thromboxane B2; D002784:Cholesterol; D010959:Tissue Plasminogen Activator