D-Galactosamine-induced cell damage enhances specific binding of prostaglandin E1 to rat hepatocytes

Matsumoto, Masami; Kikuchi, Eiryo; Okamoto, Yasuyuki; Morimura, Masashi; Kohno, Hiroyuki; Fukui, Hiroshi; Nakano, Hiroshi; Tsujii, Tadasu

doi:10.1016/0006-291x(92)90639-3

Cited by 6 publications

(1 citation statement)

References 17 publications

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“…First, it has been shown that in vim binding of PGE, to rat hepatocytes is enhanced by D-GalN. 37 Second, PGEz receptors in rat.hepatocytes are downregulated by high levels of PGEZ," An indirect effect of PGEl in hepatocytes through Kupffer cells could also be involved in PGE, protection during D-GalN-induced toxicity. Several studies have demonstrated that PGE is capable of reducing in oim TNF-a release from US-stimulated Kupffer cells3-l and peritoneal ma~rophages.~~.~' All those studies assumed that this effect of PGEl was related to CAMP formation.…”

Section: Effect Of Tnf-a Administration Tomentioning

confidence: 99%

Effect of PGE₁ on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats

Muntané¹,

Montero

Marchal

et al. 1998

J of Gastro and Hepatol

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Prostaglandin E1 has hepatoprotective properties in several clinical and experimental models of liver dysfunction. Hepatotoxicity induced by D-galactosamine (D-GalN) is a suitable animal model of human acute hepatic failure. The aim of the study was to investigate if prostaglandin E1 (PGE1) protection against hepatic D-GalN-induced apoptosis was related to tumour necrosis factor-alpha (TNF-alpha) content in serum. This cytokine is associated with in vitro apoptosis and general inflammatory disorders. In this study, PGE1 was administered 30 min before D-GalN to rats. In other experiments, several doses of TNF-alpha were administered 15min after PGE1 to D-Ga1N-treated rats. Several parameters related to apoptosis and necrosis were measured by flow cytometry, gel electrophoresis, biochemical analysis, and optical and electron microscopy. Tumour necrosis factor-alpha was quantified by competitive enzyme-linked immunosorbent assay (ELISA). PGE1 by itself did not modify the cell cycle of hepatocytes and liver toxicity, but increased TNF-alpha in serum in comparison with the control group. D-Galactosamine increased the percentage of hepatocytes in apoptosis and in the S phase of the cell cycle, and decreased those in G0/G1. Such an increase of hepatocytes in apoptosis was correlated with a higher number of apoptotic bodies and DNA fragmentation in liver than control samples. Also, D-GalN increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and TNF-alpha in serum compared with the control group. Pre-administration of PGE1 to D-GalN-treated rats reduced all the parameters of apoptosis and necrosis in liver, and increased additionallyTNF-alpha content in serum. In those experiments where low doses of TNF-alpha were administered to PGE1 and D-GalN-treated rats an inverse relationship appeared between TNF-alpha and ALT content in serum. In conclusion, the protective effects of PGE1 on D-GalN-induced apoptosis may be linked to its capacity to modulate cell division and/or its immunomodulatory activity. In this sense, our experimental results suggest that TNF-alpha could be involved in protection or exacerbation of liver damage in relation to the pathophysiological status of the liver.

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Section: Effect Of Tnf-a Administration Tomentioning

confidence: 99%

Effect of PGE₁ on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats

Muntané¹,

Montero

Marchal

et al. 1998

J of Gastro and Hepatol

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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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Inhibition of Transforming Growth Factor-β1 and UV Light-Induced Apoptosis by Prostanoids in Primary Cultures of Rat Hepatocytes

Kroll¹,

Kunz²,

Tu³

et al. 1998

Toxicology and Applied Pharmacology

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D-Galactosamine-induced cell damage enhances specific binding of prostaglandin E1 to rat hepatocytes

Cited by 6 publications

References 17 publications

Effect of PGE₁ on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats

Effect of PGE₁ on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats

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

Inhibition of Transforming Growth Factor-β1 and UV Light-Induced Apoptosis by Prostanoids in Primary Cultures of Rat Hepatocytes

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D-Galactosamine-induced cell damage enhances specific binding of prostaglandin E1 to rat hepatocytes

Cited by 6 publications

References 17 publications

Effect of PGE1 on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats

Effect of PGE1 on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats

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

Inhibition of Transforming Growth Factor-β1 and UV Light-Induced Apoptosis by Prostanoids in Primary Cultures of Rat Hepatocytes

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Effect of PGE₁ on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats

Effect of PGE₁ on TNF‐α status and hepatic D‐galactosamine‐induced apoptosis in rats