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Hepatic Apoptosis (hepatic + apoptosi)
Selected AbstractsAlcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic necrosis after ischemia-reperfusion in ratHEPATOLOGY, Issue 2 2000Shinwa Yamada M.D. Primary graft nonfunction of steatotic liver allograft is one of the factors causing shortage of donor livers. Ischemia/reperfusion (I/R) injury is an important contributory factor to primary graft nonfunction. In this study, we investigated the complex chain of events from transcription factor activation to necrosis through cytokine induction and apoptosis in steatotic rat liver after warm I/R. Rats with alcoholic or nonalcoholic fatty liver were subjected to hepatic warm I/R and compared with control rats. Rats fed an ethanol diet for 6 to 8 weeks developed severe hepatic necrosis accompanied by increased neutrophil recruitment after I/R, compared with rats with nonalcoholic fatty liver or control. Hepatic apoptosis as assessed by DNA fragmentation at 4 hours after I/R, however, increased to a similar degree in each of the 2 fatty liver models compared with the control. Alcoholic fatty liver exposed to I/R showed a rapid increase in nuclear factor-,B (NF-,B) binding activity at 1 hour after I/R, which preceded an increased expression of tumor necrosis factor , (TNF-,) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In contrast, nonalcoholic fatty liver did not show such potentiation of either NF-,B activation or cytokine induction after I/R. Our results have indicated that alcoholic fatty liver may differentially induce CINC-1 production and hepatic necrosis after I/R. Furthermore, our results suggest that apoptosis per se does not always lead to necrosis in the liver following I/R. [source] Foxf1 +/, mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injuryHEPATOLOGY, Issue 1 2003Vladimir V. Kalinichenko Previous studies have shown that haploinsufficiency of the splanchnic and septum transversum mesoderm Forkhead Box (Fox) f1 transcriptional factor caused defects in lung and gallbladder development and that Foxf1 heterozygous (+/,) mice exhibited defective lung repair in response to injury. In this study, we show that Foxf1 is expressed in hepatic stellate cells in developing and adult liver, suggesting that a subset of stellate cells originates from septum transversum mesenchyme during mouse embryonic development. Because liver regeneration requires a transient differentiation of stellate cells into myofibroblasts, which secrete type I collagen into the extracellular matrix, we examined Foxf1 +/, liver repair following carbon tetrachloride injury, a known model for stellate cell activation. We found that regenerating Foxf1 +/, liver exhibited defective stellate cell activation following CCl4 liver injury, which was associated with diminished induction of type I collagen, ,,smooth muscle actin, and Notch-2 protein and resulted in severe hepatic apoptosis despite normal cellular proliferation rates. Furthermore, regenerating Foxf1 +/, livers exhibited decreased levels of interferon-inducible protein 10 (IP-10), delayed induction of monocyte chemoattractant protein 1 (MCP-1) levels, and aberrantly elevated expression of transforming growth factor ,1. In conclusion, Foxf1 +/, mice exhibited abnormal liver repair, diminished activation of hepatic stellate cells, and increased pericentral hepatic apoptosis following CCl4 injury. [source] Yin-Chen-Hao-Tang ameliorates obstruction-induced hepatic apoptosis in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2007Tzung-Yan Lee The accumulation of hydrophobic bile acids in the liver is considered to play a pivotal role in the induction of apoptosis of hepatocytes during cholestasis. Thus, factors that affect apoptosis may be used to modulate liver fibrosis. Yin-Chen-Hao-Tang (YCHT) decoctions have been recognised as a hepatoprotective agent for jaundice and various types of liver diseases. We used an experimental rat model of bile-duct ligation (BDL) to test whether YCHT plays a regulatory role in the pathogenesis of hepatic apoptosis. BDL-plus-YCHT groups received 250 or 500 mg kg,1 YCHT by gavage once daily for 27 days. YCHT significantly ameliorated the portal hypertensive state and serum TNF-, compared with the vehicle-treated control group. In BDL-plus-YCHT-treated rats, hepatic glutathione contents were significantly higher than than in BDL-only rats. BDL caused a prominent liver apoptosis that was supported by an increase in Bax and cytochrome c protein and increased expression of Bax and Bcl-2 messenger RNA. The normalising effect of YCHT on expression of Bax and Bcl-2 mRNA was dependent on the dose of YCHT, 500 mg kg,1 having the greater effect on both Bax and Bcl-2 of mRNA levels. Additionally, YCHT treatment down-regulated both hepatic caspase-3 and ,8 activities of BDL rats. This study demonstrates the anti-apoptotic properties of YCHT and suggests a potential application of YCHT in the clinical management of hepatic disease resulting from biliary obstruction. [source] Hepatocyte growth factor protects against Fas-mediated liver apoptosis in transgenic miceLIVER INTERNATIONAL, Issue 10 2009Hideyuki Suzuki Abstract Background: Apoptosis via the Fas/Fas ligand signalling system plays an important role in the development of various liver diseases. The administration of an agonistic anti-Fas antibody to mice causes massive hepatic apoptosis and fulminant hepatic failure. Several growth factors including hepatocyte growth factor (HGF) have been found to prevent apoptosis. Methods: In this study, we demonstrated the overexpression of HGF to have a protective effect on Fas-mediated hepatic apoptosis using a transgenic mice (Tg mice) model. Results: In HGF Tg mice, the elevation of alanine aminotransferase was dramatically inhibited at 12 and 24 h after the administration of 0.15 mg/kg anti-Fas antibody. HGF Tg mice showed a significantly lower number of apoptotic hepatocytes at 12 h compared with wild-type (WT) mice. Furthermore, 85% (six of seven) HGF Tg mice were able to survive after the administration of 0.3 mg/kg anti-Fas antibody, while none of the WT mice survived. The Bcl-xL expression was increased in HGF Tg mice, while there was no difference in the expression of Bax, Bid, Mcl-1 and bcl-2 between WT mice and HGF Tg mice. In addition, the HGF Tg mice showed more Akt phosphorylation than the WT mice both before and after the anti-Fas antibody injection. Conclusions: Taken together, our findings suggest that HGF protects against Fas-mediated liver apoptosis in vivo, and the upregulation of Bcl-xL via Akt activation may also play a role in the protective effects of HGF. [source] | ||||||||||