DIETARY JUNIPER BERRY OIL MINIMIZES HEPATIC REPERFUSION INJURY IN THERAT

Juniper berry oil is rich in 5,11,14-eicosatrienoic acid, a polyunsatu rated fatty acid similar to one found in fish oil, yet less prone to p eroxidation. Dietary fish oil treatment has been shown to effectively reduce reperfusion injury; therefore, the effects of a diet containing juniper berry oil on hepatic reperfusion injury in a low-flow reflow reperfusion model were investigated in the rat. Rats were fed semisynt hetic diets containing either juniper berry oil, fish oil, or corn oil for 14 to 16 days. Daily food consumption averaged around 20 g/d in b oth the control and treatment groups; average daily weight gain was ar ound 4 g per 100 g rat weight in all three groups studied, and there w ere no significant differences in these parameters. Livers were initia lly perfused at low-flow rates to induce pericentral hypoxia followed by a 40-minute reperfusion period. Peak lactate dehydrogenase (LDH) re lease during reflow averaged 44 U/g/h in the corn oil group and 32 U/g /h in the fish oil group, but was only 21 U/g/h as a result of juniper berry oil treatment. Malondialdehyde (MDA), an end-product of lipid p eroxidation, reached a maximum value of 62 nmol/g/h in the corn oil gr oup, but only reached 43 nmol/g/h and 34 nmol/g/h in the fish oil and juniper berry oil groups, respectively. Both juniper berry oil and fis h oil treatment improved rates of bile flow from 25 mu L/g/h (corn oil ) to 36 and 38 mu L/g/h, respectively. Importantly, juniper berry oil reduced cell death in pericentral regions of the liver lobule by 75%, Trypan blue distribution time, an indicator of the hepatic microcircul ation, was reduced by approximately 25% with fish oil and over 50% by juniper berry oil diets compared with corn oil controls. The rates of entry of fluorescein-dextran, a dye confined to the vascular space, we re increased 1.8- and 2.6-fold, and rates of outflow were increased 4, 4- and 4.3-fold by fish oil and juniper berry oil, respectively, also reflecting improved microcirculation. Juniper berry oil also blunted i ncreases in intracellular calcium and release of prostaglandin E-2 (PG E(2)) by cultured Kupffer cells stimulated by endotoxin. These results are consistent with the hypothesis that feeding a diet containing jun iper berry oil reduces reperfusion injury by inhibiting activation of Kupffer cells, thus reducing vasoactive eicosanoid release and improvi ng the hepatic microcirculation in livers undergoing oxidant stress.