Cytoprotective actions of prostacyclin during hypoxia in the isolated perfused cat liver

Abstract

The cytoprotective effect of prostacyclin (PGI2) was examined using hypoxic cat livers perfused with Krebs-Henseleit buffer at constant flow. PGI2 infusion (10 ng . g-1 . min-1) showed no direct vasodilator effect on the hepatic circulation under conditions of normoxia or hypoxia, as studied by changes in perfusion pressure. Hypoxia induced a marked decline in hepatic oxygen consumption, an increase in perfusion pressure, and in perfusate cathepsin D and LDH activity in the hepatic effluent indicating lysosomal and cytoplasmic leakage. Tissue samples, obtained 150 min after hypoxic perfusion, showed higher percent-free cathepsin values (82 +/- 4%, mean +/- SE, 7 livers, P less than 0.025) compared to that of normoxia (58 +/- 4). Phagocytic activity, measured by the clearance rate of colloidal carbon particles, was also depressed by hypoxia. PGI2 infusion significantly inhibited the posthypoxia leakage of liver cathepsin D and LDH into the recirculating perfusate, restored the percent-free cathepsin D to 64 +/- 3%, and preserved the phagocytic activity during hypoxia, indicating preservation of lysosomal and cytoplasmic membrane integrity and Kupffer cell phagocytic function. The preservation of lysosomal integrity by PGI2 was further confirmed by electron microscopy. It is evident that PGI2 has a significant protective effect in hypoxic hepatocytes that may not be related to its vasodilation and inhibition of platelet aggregation.

Protective action of hepatocyte growth factor for acute liver injury caused by D-galactosamine in transgenic mice

“…Serum levels of The protective effect of PGE 2 and PGE 1 on acute liver injury is well known. [13][14][15][16][17][18][19][20][21][22] Because biological activity of PGE 2 is almost identical to PGE 1 , 41 and PGE 2 is the main prostanoid secreted by cultured Kupffer cells, 42 we examined hepatic PGE 2 content. Cytoprotective action of PGE 2 was exerted in several kinds of liver injuries such as D-GalN, 13,19,22 carbon tetrachloride, 14,16,20 a-naphtylisothiocyanate, 15 lipopolysaccharide, 18 and immune reaction against liver antigen.…”

“…The percentage of PCNA-positive cells tocellular necrosis caused by several hepatotoxins. [13][14][15][16][17][18][19][20][21][22] It has also been reported that HGF stimulated prostaglandin E 2 in WT mice was very low at 0 hours and 24 hours after treatment, but increased at 48 hours. To clarify the mecha-(PGE 2 ) production through increases in both cytosolic phospholipase A 2 and cyclooxyganase activity in human gastric nisms via which HGF acts, we measured hepatic HGF and prostaglandin E 2 (PGE 2 ) contents after D-GalN administration carcinoma TMK-1 cells 23 and primary cultured rat hepatocytes.…”

Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion

“…Perhaps this improvement is associated with the so-called 'cytoprotective' activity of prostacyclin, which has been proposed not only in whole animals (Ogletree et al, 1979;Schror et al, 1981), but also in a variety of isolated tissues, in which the effects of prostacyclin must be due to factors other than blood flow (Araki & Lefer, 1980;Robert, 1984;Smith et al, 1984b).…”

Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs

“…In addition to these effects on platelet and vascular smooth muscle, PGI2 has been shown to possess a cytoprotective effect, which may be useful for preservation of platelets (Blackwell et al, 1982) and protection of various tissues from ischaemia or hypoxia (Ogletree et al, 1979;Araki & Lefer, 1980). Therefore, the present study was conducted to investigate whether or not beraprost has a cytoprotective effect in a canine model of transient global cerebral ischaemia.…”