Attenuation of endotoxin-induced intestinal microcirculatory damage by eicosapentanoic acid

The major objective of this study is to investigate whether oral administration of eicosapentanoic acid (EPA) has any preventive effect on endotoxin-induced microcirculatory damage of rat small intestine. EPA in a daily dose of 300 mg/kg was orally given to male Wistar rats for 3 wk. Submucosal microvessels of the ileum were observed by intravital microscopy equipped with a high-speed video camera system after the intra-arterial infusion of endotoxin at a dose of 2 mg · kg^-1 · h^-1. The number of sticking leukocytes was significantly increased at 30 min after the treatment of endotoxin especially along the smaller branch of intestinal venules. It reached the maximal plateau at 45 min after treatment. The pretreatment of EPA significantly attenuated the increase in sticking leukocytes induced by endotoxin. A platelet-activating factor (PAF) antagonist 2-[N-acetyl-N-(2- methoxy-3-octadecylcarbamoyloxy propoxycarbonyl) aminomethyl]-1- ethylpyridinium chloride (CV-6209) significantly prevented the increased leukocyte sticking to the same extent as EPA treatment. Thirty minutes after endotoxin infusion, red blood cell (RBC) velocity was significantly decreased in both arterioles and venules. RBC velocity appeared to be continuously decreased thereafter and reached its minimum value at ~60 min. EPA treatment was revealed to prevent the decrease in RBC velocity of microvessels induced by endotoxin. CV-6209 also significantly attenuated the decreased RBC velocity. The remarkable elevation of PAF content in the ileal mucosa as observed by endotoxin infusion was also significantly attenuated by administration of EPA. EPA is considered to exert its preventive effect on endotoxin-induced microcirculatory damage of the small intestine especially through the attenuation of leukocyte accumulation and overproduction of PAF.