Treatment of Experimental Thrombosis by Intravenous Infusion of Trieicosapentaenoyl Glycerol

1990 Fiscal Year Final Research Report Summary

• Project/Area Number: 63570568
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Toyama Medical and Pharmaceutical University
• Principal Investigator: HAMAZAKI Tomohito Toyama Medical and Pharmaceutical University Assistant Professor, 附属病院, 講師 (70167592)
• Project Period (FY): 1988 – 1989
• Keywords: Eicosapentaenoic acid / arachidonic acid cascade / leukotriene B / intravenous infusion / emulsion

Research Abstract

Eicosapentaenoic acid (EPA) was purified from muscle of sardine and acylated to glycerol. Trieicosapentaenoyl-glycerol (EPA-TG) syntherized this way was emulsified with egg yolk lecithin. Glycerol (2.5%) was further added to maintain osmotic pressure of the emulsion. To rabbits (3-3.5kg) was infused 30ml of the emulsion (3g EPA) through ear veins. Blood samples were obtained from ear arteries before, and 6, 24 and 168 h after the infusion. Polymorphonuclear leukocytes were prepared and stimulated calcium ionophore. The supernatant was extracted for leukotriene B_4 and B_5 (LTB4/5) and measured by high performance liquid chromatography. In the control experiments commercially available soybean oil emulsion was used instead of EPA emulsion.
Averaged LTB_4 production by leukocytes 6, 24 and 168 h after EPA infusion was 60 (p<0.05), 72 and 86% of the pre-infusion levels, respectively. LTB_5 production, which was below the detection limits before the infusion, was similar to that of LTB_4 6 h after the infusion, and then decreased afterward. In the control experiments there were no significant changes in LTB_4 production. LTB_5 production was below the detection limits throughout the control experiments.
LTB_4 (but not LTB_5) is a potent chemoattractant and aggregant of leukocytes, and intimately related with tissue damage due to acute inflammation (including acute myocardial infarction and graft rejection). Infusion of EPA can depress LTB_4 production very quickly. Consequently, EPA emulsion may be useful for the clinical situations described above.