Intravenous infusion of tridihomo-gamma-linolenoyl-glycerol reduces leukotriene B4 production in the rat and rabbit.
1. We have formulated an infusible emulsion of 10% tridihomo-gamma-linolenoyl-glycerol (94% pure) and investigated the effects of its infusion on leukotriene B4 production. 2. We infused the emulsion into the ear veins of two rabbits in a dose of 0.8g of tridihomo-gamma-linolenoyl-glycerol/kg. Polymorphonuclear leucocytes were obtained from rabbits before the infusion, and 6, 24, 72 and 168 h after. The ionophore-stimulated leukotriene B4 production by polymorphonuclear leucocytes was reduced to about 50% of baseline as early as 6 h after the infusion and remained reduced until 24 h after the infusion. 3. To closely investigate the changes in leukotriene B4 production at 6 h after the infusion, we infused 1.0 g of tridihomo-gamma-linolenoyl-glycerol/kg into the tail veins of eight male Wistar rats. Six hours later, peritoneal macrophages were obtained from four rats for the analysis of ionophore-stimulated leukotriene B4 production. Peritoneal cells and blood samples were also obtained from the remaining rats for fatty acid analysis. Another eight rats were used without prior infusion for baseline determination. 4. The production of leukotriene B4 by macrophages was significantly reduced to 42% of baseline, and the plasma free dihomo-gamma-linolenic acid was markedly increased from 0.26 to 4.82 mol%, in 6 h. 5. We conclude that the infusion of a tridihomo-gamma-linolenoyl-glycerol emulsion is able to decrease leukotriene B4 production and to increase the dihomo-gamma-linolenic acid concentrations in the plasma and peritoneal cells of rats in 6 h.
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
N
N
Nakamura
T
T
Hamazaki
H
H
Taki
K
K
Yamazaki
M
M
Kobayashi
D015126:8,11,14-Eicosatrienoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005227:Fatty Acids / Q000032:analysis / Q000097:blood; D007262:Infusions, Intravenous; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014280:Triglycerides / Q000008:administration & dosage* / Q000494:pharmacology
D005227:Fatty Acids; D014280:Triglycerides; C081568:tridihomo-gamma-linolenoylglycerol; D007975:Leukotriene B4; D015126:8,11,14-Eicosatrienoic Acid