Animals ; Cytokines ; blood ; Endotoxins ; toxicity ; Fatty Liver ; chemically induced ; Liver Failure, Acute ; chemically induced ; Male ; Rats ; Rats, Sprague-Dawley

Bee Venoms ; adverse effects ; Female ; Humans ; Insect Bites and Stings ; Liver Failure, Acute ; chemically induced ; Middle Aged

Animals ; Endotoxins ; Female ; HMGB1 Protein ; biosynthesis ; Liver Failure, Acute ; chemically induced ; metabolism ; Male ; Rats ; Rats, Wistar

Tetrachloroethylene is a chlorinated solvent that is primarily used in dry cleaning and degreasing operations. Although the hepatotoxicity caused by tetrachloroethylene has been well documented in literature, it is rarely considered as a cause of acute liver failure. We report a case of a 39-yr-old man who was admitted to our hospital for acute liver failure due to tetrachloroethylene exposure. Histological examination of the liver revealed massive hepatic necrosis, prominently, in zone 3 of the hepatic lobules. The patient underwent supportive treatment along with 3 sessions of plasmapheresis, and consequently, he presented a favorable outcome. Repeat liver biopsy performed 6 months after the patient's discharge showed architectural distortion with postnecrotic cirrhosis. Physicians should be aware of the possibility of acute liver failure induced by tetrachloroethylene. Early plasmapheresis can be effective for individuals with sufficient capacity for hepatocyte regeneration.
Adult ; Carcinogens/*toxicity ; Humans ; Liver Cirrhosis/pathology ; Liver Failure, Acute/chemically induced/*diagnosis/pathology ; Male ; *Occupational Exposure ; Plasmapheresis ; Tetrachloroethylene/*toxicity

Objective: To explore the new mechanism of liver fibrosis through D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced necroptosis as an entry point to inhibit lethal injury. Methods: The carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis was established. At 6 weeks of fibrosis, the mice were challenged with a lethal dose of D-GalN/LPS, and the normal mice treated with the same treatment were used as the control. The experiment was divided into four groups: control group (Control), acute injury group (D-GalN/LPS), liver fibrosis group (Fib), and liver fibrosis + acute challenge group (Fib + D-GalN/LPS). Quantitative PCR and immunofluorescence were used to analyze the expression of necroptosis key signal molecules RIPK1, RIPK3, MLKL and/or P-MLKL in each group. Normal mice were treated with inhibitors targeting key signaling molecules of necroptosis, and then given an acute challenge. The inhibitory effect of D-GalN/LPS-induced-necroptosis on acute liver injury was evaluated according to the changes in transaminase levels and liver histology. Liver fibrosis spontaneous ablation model was established, and then acute challenge was given. Necroptosis key signal molecules expression was analyzed in liver tissue of mice in each group and compared by immunohistochemistry. The differences between groups were compared with t-test or analysis of variance. Results: Quantitative PCR and immunofluorescence assays result showed that D-GalN/LPS-induced significant upregulation of RIPK1, RIPK3, MLKL and/or P-MLKL. Necroptosis key signal molecules inhibition had significantly reduced D-GalN/LPS-induced liver injury, as manifested by markedly reduced serum ALT and AST levels with improvement in liver histology. Necroptosis signaling molecules expression was significantly inhibited in fibrotic livers even under acute challenge conditions. Additionally, liver fibrosis with gradual attenuation of fibrotic ablation had inhibited D-GalN/LPS-induced necroptosis. Conclusion: Liver fibrosis may protect mice from acute lethal challenge injury by inhibiting D-GalN/LPS-induced necroptosis.
Animals ; Chemical and Drug Induced Liver Injury/pathology* ; Galactosamine/adverse effects* ; Lipopolysaccharides/adverse effects* ; Liver/pathology* ; Liver Cirrhosis/pathology* ; Liver Failure, Acute/chemically induced* ; Mice ; Necroptosis

Animals ; Disease Models, Animal ; Ephedra ; chemistry ; Galactosamine ; Lipopolysaccharides ; Liver Failure, Acute ; chemically induced ; drug therapy ; Protective Agents ; pharmacology ; Rats

Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Chemical and Drug Induced Liver Injury ; etiology ; Humans ; Liver Failure, Acute ; chemically induced ; Sulfonamides ; adverse effects

OBJECTIVETo establish a practical and reproducible animal model of human acute-on-chronic liver failure for further study of the pathophysiological mechanism of acute-on-chronic liver failure and for drug screening and evaluation in its treatment.

METHODSImmunological hepatic fibrosis was induced by human serum albumin in Wistar rats. In rats with early-stage cirrhosis (fibrosis stage IV), D-galactosamine and lipopolysaccharide were administered. Mortality and survival time were recorded in 20 rats. Ten rats were sacrificed at 4, 8, and 12 hours. Liver function tests and plasma cytokine levels were measured after D-galactosamine/lipopolysaccharide administration and liver pathology was studied. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.

RESULTSMost of the rats treated with human albumin developed cirrhosis and fibrosis, and 90% of them died from acute liver failure after administration of D-galactosamine/lipopolysaccharide, with a mean survival time of (16.1+/-3.7) hours. Liver histopathology showed massive or submassive necrosis of the regenerated nodules, while fibrosis septa were intact. Liver function tests were compatible with massive necrosis of hepatocytes. Plasma level of TNFalpha increased significantly, parallel with the degree of the hepatocytes apoptosis. Plasma IL-10 levels increased similarly as seen in patients with acute-on-chronic liver failure.

CONCLUSIONWe established an animal model of acute-on-chronic liver failure by treating rats with human serum albumin and later with D-galactosamine and lipopolysaccharide. TNFalpha-mediated liver cell apoptoses plays a very important role in the pathogenesis of acute liver failure.

Animals ; Disease Models, Animal ; Female ; Galactosamine ; adverse effects ; Humans ; Lipopolysaccharides ; adverse effects ; Liver Failure, Acute ; chemically induced ; Rats ; Rats, Wistar ; Serum Albumin ; adverse effects

Acetaminophen ; adverse effects ; Child ; Female ; Humans ; Integrative Medicine ; Liver Failure, Acute ; blood ; chemically induced ; drug therapy ; Medicine ; Medicine, Chinese Traditional ; Western World

OBJECTIVETo compare the effects of different approaches to establishing rat models of acute liver failure (ALF).

METHODSSixty-eight Sprague-Dawley rats were randomly divided into 3 groups for establishing ALF models using 3 different approaches, namely conventional hepatectomy for resecting 90% liver tissue as described by Higgins and Anderson, modified bloodless hepatectomy for resecting 90% liver tissue, and intraperitoneal injections of 700 mg/kg D-galactosamine (D-gal) and 5 µg/kg lipopolysaccharide (LPS). The mortality of the rats due to postoperative bleeding and survival rate at 7 days after the surgery were recorded. The levels of alanine aminotransferase (ALT), total bilimbin (Tbil), albumin (ALB), NH3, glucose (Glu) and prothrombin time (PT) were monitored, and histopathologies of the liver were examined at 24 and 72 h after the surgery.

RESULTSThe mortality rate due to postoperative bleeding was higher in conventional hepatectomy group than in the modified surgical group (15% vs 0). The survival rate at 7 days was 25%, 0%, 15% in conventional surgical group, modified surgical group and drug injection group, respectively. In the latter two groups, significant changes of ALT, Tbil, ALB, NH3, Glu, and PT were recorded at 24 and 72 h after the modeling (P<0.05), and these changes were the most obvious at 24 h in modified surgical group and at 72 h in the drug injection group; ALB in both groups declined to the lowest at 7 days and then increased gradually. Liver cell degeneration and necrosis were found in modified surgical group and drug injection group at 24 h and 72 h after the modeling.

CONCLUSIONBoth the modified 90% bloodless hepatectomy and injections of D-gal and LPS can be used to establish ideal rat models of ALF to suit different ALF-related researches.

Animals ; Disease Models, Animal ; Galactosamine ; adverse effects ; Hepatectomy ; Injections, Intraperitoneal ; Lipopolysaccharides ; adverse effects ; Liver Failure, Acute ; chemically induced ; pathology ; Rats ; Rats, Sprague-Dawley