Studies on the mechanism of the protective action of 16,16-dimethyl PGE2 in carbon tetrachloride induced acute hepatic injury in the rat

Rush, Bob D.; Merritt, Margaret V.; Kaluzny, Margaret; Schoick, Tim Van; Brunden, Marshall N.; Ruwart, Mary J.

doi:10.1016/0090-6980(86)90011-0

Cited by 30 publications

(11 citation statements)

References 27 publications

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“…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.…”

Section: Effect Of Anti-pge 2 Antibody On D-galn -Induced Livermentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

1997

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Hepatocyte growth factor (HGF) has been reported to beHepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes and plays a pivotal role in liver regeneraa potent mitogen for hepatocytes in vivo and in vitro. Recent reports have shown that HGF has cytoprotective actions in tion after liver injury. HGF was identified from the serum of partially hepatectomized rats, 1 rat platelets, 2 rabbit serum, 3 acute liver injury models, but its mechanisms remain to be resolved. In the present study, we investigated whether HGF the human plasma of fulminant hepatic failure, 4 and human lung fibroblasts.5 Numerous investigations of HGF have recould work as an anti-hepatitis agent for acute liver injury caused by D-galactosamine (D-GalN) using transgenic (TG) vealed that HGF has pleiotropic functions such as a mitogen, a morphogen, a motogen, and a tumor suppressor. [6][7][8] Remice expressing HGF in hepatocytes, compared with wildtype (WT) mice of their siblings. After administration of 3 g/ cently, it has been reported that HGF works as an antihepatitis agent against acute liver injuries of in vivo and in kg body weight of D-GalN, elevated serum transaminase levels and severe liver damage that were observed in WT mice were vitro models, 9-12 but its exact mechanisms remain to be clarified. significantly improved in TG mice. In TG mice, the percentage of proliferating cell nuclear antigen (PCNA)-positive hepatoIt has been reported that prostaglandins, which are metabolites of arachidonic acid, act as a cytoprotector against hepacytes was high at 0 hours after D-GalN treatment, and increased at 24 hours. 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. 24 These data are indicative of a close relationship beby an enzyme immunoassay. Total hepatic HGF contents, which were composed of murine (endogeneous) and human tween HGF and PGE 2 .In our previous reports, we examined the important role (derived from transgene) HGF, in TG mice were higher than those in WT mice at 0, 12, and 24 hours after administration of HGF in liver regeneration by using transgenic mice expressing HGF persistently in hepatocytes under the control of 3 g/kg body weight of D-GalN. Hepatic PGE 2 contents in TG mice were also significantly higher than those in WT of albumin regulatory sequences. 25,26 In those reports, we showed that the livers of HGF transgenic mice recovered mice. Hepatic PGE 2 contents had a positive correlation with total HGF contents at both 12 hours and 24 hours after the ...

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Section: Effect Of Anti-pge 2 Antibody On D-galn -Induced Livermentioning

confidence: 99%

mentioning

confidence: 99%

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

1997

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“…PGs have been shown to have a beneficial effect in a variety of animal models of hepatic failure due to toxins (CCl4, acetaminophen, galactosamine, or alcohol), hypoxia, ischemia, and immune-mediated diseases (25)(26)(27)(28)(29)(30)(31). PGs are primarily derived from arachidonic acid, which is released from membrane phospholipids by the action of phospholipases.…”

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confidence: 99%

Cyclopentenone Prostaglandins as Potential Inducers of Phase II Detoxification Enzymes

Kawamoto¹,

Nakamura²,

Naito

et al. 2000

Journal of Biological Chemistry

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Exposure of cells to a wide variety of chemoprotective compounds confers resistance to a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes, such as glutathione S-transferases (GSTs). In the present study, we developed a cell culture system that potently responds to phenolic antioxidants and found that antitumor prostaglandins (PGs) are potential inducers of GSTs. We screened primary hepatocytes and multiple cell lines for inducing GST activity upon incubation with the phenolic antioxidant (tert-butylhydroquinone) and found that rat liver epithelial RL34 cells most potently responded. Based on an extensive screening of diverse chemical agents on the induction of GST activity in RL34 cells, the J2 series of PGs, 15-deoxy-⌬ 12,14 -prostaglandin J2 (15-deoxy-⌬ 12,14 -PGJ2) in particular, were found to be potential inducers of GST. Enhanced gene expression of Class GST isozyme (GSTP1) by 15-deoxy-⌬ 12,14 -PGJ2 was evident as a drastic elevation of the mRNA level. Hence, we examined the molecular mechanism underlying the 15-deoxy-⌬ 12,14 -PGJ2-induced GSTP1 gene expression. From functional analysis of various deletion mutant genes, we found that the 15-deoxy-⌬ 12,14 -PGJ2 reponse element was localized in a region containing a GSTP1 enhancer I (GPEI) that consists of two imperfect phorbol 12-Otetradecanoylphorbol-13-acetate response elements. When the GPEI was combined with the minimum GSTP1 promoter, the element indeed showed an enhancer activity in response to 15-deoxy-⌬ 12,14 -PGJ2. Point mutations of either of the two imperfect 12-O-tetradecanoylphorbol-13-acetate response elements in GPEI completely abolished the enhancer activity. Gel mobility shift assays demonstrated that 15-deoxy-⌬ 12,14 -PGJ2 specifically stimulated the binding of nuclear proteins including the transcription factor c-Jun, but not Nrf2, to GPEI. These results suggest that 15-deoxy-⌬ 12,14 -PGJ2 induces the expression of the rat GSTP1 gene through binding of proteins, including c-Jun, to a specific GPEI.

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“…Prostaglandin analogs dmPGE 2, PGI2 and PGF2~ have been shown to have hepatoprotective properties in CC14-induced liver injury (Guarner et al, 1983;Rush et al, 1986;Stachura et al, 1981). It has been suggested that the protection offered by prostaglandins could result from their effect on liver microcirculation.…”

Section: Liver Injury Induced By Chemicalsmentioning

confidence: 99%

Hepatic circulation: Potential for therapeutic intervention

Ballet

1990

Pharmacology & Therapeutics

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In recent years, knowledge of the physiology and pharmacology of hepatic circulation has grown rapidly. Liver microcirculation has a unique design that allows very efficient exchange processes between plasma and liver cells, even when severe constraints are imposed upon the system, i.e. in stressful situations. Furthermore, it has been recognized recently that sinusoids and their associated cells can no longer be considered only as passive structures ensuring the dispersion of molecules in the liver, but represent a very sophisticated network that protects and regulates parenchymal cells through a variety of mediators. Finally, vascular abnormalities are a prominent feature of a number of liver pathological processes, including cirrhosis and liver cell necrosis whether induced by alcohol, ischemia, endotoxins, virus or chemicals. Although it is not clear whether vascular lesions can be the primary events that lead to hepatocyte injury, the main interest of these findings is that liver microcirculation could represent a potential target for drug action in these conditions.

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Studies on the mechanism of the protective action of 16,16-dimethyl PGE2 in carbon tetrachloride induced acute hepatic injury in the rat

Cited by 30 publications

References 27 publications

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

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

Cyclopentenone Prostaglandins as Potential Inducers of Phase II Detoxification Enzymes

Hepatic circulation: Potential for therapeutic intervention

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