cytochrome-c-t and Liver-Failure--Acute

To assess the effects of dihydromyricetin (DHM) as a hepatoprotective candidate in reducing hepatic injury and accelerating hepatocyte proliferation after carbon tetrachloride (CCl4) treatment.. C57 BL/6 mice were used in this study. Mice were orally administered with DHM (150 mg/kg) for 4 d after CCl4 treatment. Serum and liver tissue samples were collected on days 1, 2, 3, 5 and 7 after CCl4 treatment. The anti-inflammatory effect of DHM was assessed directly by hepatic histology detection and indirectly by serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and superoxide dismutase (SOD). Inflammatory cytokines, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), were detected using ELISA kits. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of DHM in promoting hepatocyte proliferation. Hepatocyte apoptosis was measured by TUNEL assay. Furthermore, apoptosis proteins Caspases-3, 6, 8, and 9 were detected by Western blot. SP600125 were used to confirm whether DHM regulated liver regeneration through JNK/TNF-α pathways.. DHM showed a strong anti-inflammatory effect on CCl4-induced liver injury in mice. DHM could significantly decrease serum ALT, AST, IL-1β, IL-6 and TNF-α and increase serum albumin, SOD and liver SOD compared to the control group after CCl4 treatment (P < 0.05). PCNA results indicated that DHM could significantly increase the number of PCNA positive cells compared to the control (348.9 ± 56.0 vs 107.1 ± 31.4, P < 0.01). TUNEL assay showed that DHM dramatically reduced the number of apoptotic cells after CCl4 treatment compared to the control (365.4 ± 99.4 vs 90.5 ± 13.8, P < 0.01). Caspase activity detection showed that DHM could reduce the activities of Caspases- 8, 3, 6 and 9 compared to the control (P < 0.05). The results of Western blot showed that DHM increased the expression of JNK and decreased TNF-α expression. However, DHM could not affect TNF-α expression after SP600125 treatment. Furthermore, DHM could significantly improve the survival rate of acute liver failure (ALF) mice (73.3% vs 20.0%, P < 0.0001), and SP600125 could inhibit the effect of DHM.. These findings demonstrate that DHM alleviates CCl4-induced liver injury, suggesting that DHM is a promising candidate for reversing liver injury and ALF.

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Carbon Tetrachloride; Caspase Inhibitors; Cell Proliferation; Chemical and Drug Induced Liver Injury; Cytochromes c; Disease Models, Animal; Flavonols; Inflammation Mediators; JNK Mitogen-Activated Protein Kinases; Liver; Liver Failure, Acute; Liver Regeneration; Male; Mice, Inbred C57BL; Mitochondria, Liver; Protein Kinase Inhibitors; Signal Transduction; Time Factors; Tumor Necrosis Factor-alpha

Cryptotanshinone from Salvia miltiorrhiza Bunge was investigated for hepatoprotective effects in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Cryptotanshinone (20 or 40 mg/kg) was orally administered 12 and 1h prior to GalN (700 mg/kg)/LPS (10 μg/kg) injection. The increased mortality and TNF-α levels by GalN/LPS were declined by cryptotanshinone pretreatment. In addition, cryptotanshinone attenuated GalN/LPS-induced apoptosis, characterized by the blockade of caspase-3, -8, and -9 activation, as well as the release of cytochrome c from the mitochondria. In addition, cryptotanshinone significantly suppressed JNK, ERK and p38 phosphorylation induced by GalN/LPS, and phosphorylation of TAK1 as well. Furthermore, cryptotanshinone significantly inhibited the activation of NF-κB and suppressed the production of proinflammatory cytokines. These findings suggested that hepatoprotective effect of cryptotanshinone is likely associated with its anti-apoptotic activity and the down-regulation of MAPKs and NF-κB associated at least in part with suppressing TAK1 phosphorylation.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Aspartate Aminotransferases; Caspases; Chemical and Drug Induced Liver Injury; Cytochromes c; Galactosamine; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mitochondria; Mitogen-Activated Protein Kinases; NF-kappa B; Phenanthrenes; Phytotherapy; Plant Extracts; Salvia miltiorrhiza; Tumor Necrosis Factor-alpha

A compound was isolated from Potentilla chinensis, and it was identified as tormentic acid (TA) based on its physicochemical properties and spectral data. The hepatoprotective effect of TA was evaluated using an acute liver failure model induced by lipopolysaccharide (LPS)/D-galactosamine (D-GalN). The results revealed that TA significantly prevented LPS/D-GalN-induced fulminant hepatic failure, as evidenced by the decrease in serum aminotransferase and total bilirubin activities and the attenuation of histopathological changes. TA alleviated the pro-inflammatory cytokines including TNF-α and NO/iNOS by inhibiting nuclear factor-κB (NF-κB) activity. Moreover, TA strongly inhibited lipid peroxidation, recruited the anti-oxidative defense system, and increased HO-1 activity. In addition, TA significantly attenuated increases in TUNEL-positive hepatocytes through decreasing the levels of cytochrome c, as well as caspases-3, 8 and 9, while augmenting the expression of Bcl-2. In conclusion, TA protects hepatocytes against LPS/D-GalN-induced injury by blocking NF-κB signaling pathway for anti-inflammatory response and attenuating hepatocellular apoptosis. Consequently, TA is a potential agent for preventing acute liver injury and may be a major bioactive ingredient of Potentilla chinensis.

Topics: Animals; Anti-Inflammatory Agents; Caspases; Cytochromes c; Cytokines; Galactosamine; Heme Oxygenase-1; Lipid Peroxidation; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; Phytotherapy; Potentilla; Protective Agents; Proto-Oncogene Proteins c-bcl-2; Transcription Factor RelA; Triterpenes

Linarin was isolated from Chrysanthemum indicum L. Fulminant hepatic failure is a serious clinical syndrome that results in massive inflammation and hepatocyte death. Apoptosis is an important cellular pathological process in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury, and regulation of liver apoptosis might be an effective therapeutic method for fulminant hepatic failure. This study examined the cytoprotective mechanisms of linarin against GalN/LPS-induced hepatic failure. Mice were given an oral administration of linarin (12.5, 25 and 50mg/kg) 1h before receiving GalN (800 mg/kg)/LPS (40 μg/kg). Linarin treatment reversed the lethality induced by GalN/LPS. After 6h of GalN/LPS injection, the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor (TNF)-α, interleukin-6 and interferon-γ were significantly elevated. GalN/LPS increased toll-like receptor 4 and interleukin-1 receptor-associated kinase protein expression. These increases were attenuated by linarin. Linarin attenuated the increased expression of Fas-associated death domain and caspase-8 induced by GalN/LPS, reduced the cytosolic release of cytochrome c and caspase-3 cleavage induced by GalN/LPS, and reduced the pro-apoptotic Bim phosphorylation induced by GalN/LPS. However, linarin increased the level of anti-apoptotic Bcl-xL and phosphorylation of STAT3. Our results suggest that linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways.

Topics: Alanine Transaminase; Animals; Apoptosis; Apoptosis Regulatory Proteins; Aspartate Aminotransferases; Bcl-2-Like Protein 11; bcl-X Protein; Caspase 3; Caspase 8; Cytochromes c; Cytoprotection; Cytosol; Fas-Associated Death Domain Protein; Galactosamine; Glycosides; Interferon-gamma; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Membrane Proteins; Mice; Phosphorylation; Proteolysis; Proto-Oncogene Proteins; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Increasing evidence suggests that the inactivation of cathepsin B attenuates hepatocyte apoptosis and liver damage. This study aimed to investigate the protective effects of a cathepsin B inhibitor (CA-074me) on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute hepatic failure (AHF) in mice.. Mice were intraperitoneally injected with a combination of LPS/D-GalN to induce AHF with or without CA-074me pretreatment. The cumulative survival rates were calculated 48 hours after the induction of AHF. As well as changes in biochemical indicators and liver histology, hepatocyte apoptosis was assessed using a TUNEL method. Serum tumor necrosis factor-alpha (TNF-alpha) production, caspase-3, caspase-8, and caspase-9 activity was evaluated. Cytosolic cytochrome c and Bcl-2 expression were measured by Western blotting.. The marked elevation in serum aminotransferase activity and prothrombin time found in LPS/D-GalN-treated mice was significantly improved by pretreatment with CA-074me. The efficacy of CA-074me was also confirmed by histological analysis and TUNEL assay. The survival rate significantly improved in LPS/D-GalN-induced mice given CA-074me compared with untreated mice. LPS/D-GalN-induced caspase-3 and caspase-9 activation was remarkably suppressed by CA-074me. However, the increased levels of serum TNF-alpha and elevated caspase-8 activity in AHF mice were not significantly reduced by CA-074me. Moreover, CA-074me sharply reduced the increased expression of cytosolic cytochrome c and markedly augmented Bcl-2 expression.. These results suggest that CA-074me has a protective effect in acute hepatic failure induced by LPS/D-GalN.

Topics: Animals; Apoptosis; Caspases; Cathepsin B; Cysteine Proteinase Inhibitors; Cytochromes c; Dipeptides; Galactosamine; In Situ Nick-End Labeling; Injections, Intraperitoneal; Lipopolysaccharides; Liver Failure, Acute; Male; Mice; Mice, Inbred Strains; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Survival Rate; Transaminases; Tumor Necrosis Factor-alpha

Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure and is primarily caused by cytochrome P450 (CYP) 2E1-driven conversion of APAP into hepatotoxic metabolites. Several reports showed that melatonin attenuated APAP-induced acute liver failure. Nevertheless, the exact mechanism remains obscure. In the present study, we investigated the effects of melatonin on apoptosis-inducing factor (AIF)-dependent cell death in APAP-induced acute liver failure. Mice were intraperitoneally (i.p.) injected with different doses of melatonin (1.25, 5, 20 mg/kg) 30 min before APAP (300 mg/kg, i.p.). As expected, melatonin significantly alleviated APAP-induced cell death, as determined by TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. Further analysis showed that melatonin significantly attenuated APAP-induced activation of the serine/threonine kinase receptor interacting protein 1 (RIP1). In addition, melatonin inhibited APAP-induced hepatic c-Jun N-terminal kinase (JNK) phosphorylation and mitochondrial Bax translocation. Correspondingly, melatonin inhibited APAP-induced translocation of AIF from mitochondria to nuclei. Interestingly, no changes were induced by melatonin on hepatic CYP2E1 expression. In addition, melatonin had little effect on APAP-induced hepatic glutathione (GSH) depletion. In conclusion, melatonin protects against AIF-dependent cell death during APAP-induced acute liver failure through its direct inhibition of hepatic RIP1 and subsequent JNK phosphorylation and mitochondrial Bax translocation.

Topics: Acetaminophen; Animals; Antioxidants; Apoptosis Inducing Factor; Cell Death; Cytochrome P-450 CYP2E1; Cytochromes c; Enzyme Activation; Glutathione; GTPase-Activating Proteins; Hepatocytes; JNK Mitogen-Activated Protein Kinases; Liver Failure, Acute; Male; Melatonin; Mice; Phosphorylation; Protein Transport

Acute liver failure is a devastating illness of various causes with considerable mortality. Hepatic stimulator substance (HSS) has been suggested for use as a protective agent against acute hepatic injury induced by chemical poisons because it has a variety of biological activities. However, the mechanism whereby HSS protects against hepatotoxins is poorly understood. In this study, we established a hepatic gene transfer system via hydrodynamic tail vein injection to deliver a naked plasmid containing the human HSS gene (hHSS) and analyzed HSS-mediated protection of the liver during fulminant hepatic failure (FHF) induced by D-galactosamine (D-gal) and lipopolysaccharide (LPS). The results showed that the reporter gene, enhanced green fluorescent protein, was efficiently expressed in the liver of BALB/c mice. Hydrodynamic-based transfection of hHSS yielded a 70% survival rate compared with 36.7% for the control group at 24 h after D-gal/LPS treatment. In addition, hHSS expression preserved liver morphology and function. It is noteworthy that hHSS hydrodynamic-based transfer ameliorated indices of the mitochondrial permeability transition (MPT) resulting from the toxic effects of d-gal/LPS on the liver such as mitochondrial swelling, mitochondrial transmembrane potential disruption, and cytochrome c translocation. Furthermore, mitochondrial morphology and ATP levels were maintained in hHSS-administered mice. HSS-mediated protection was similar to that observed with the MPT inhibitor N-methyl-4-isoleucine-cyclosporin (NIM811), indicating a possible role for HSS in the regulation of MPT. In conclusion, a single dose of hHSS plasmid protected mice from FHF, and this hepatoprotective effect seemed to correlate with the inhibition of MPT.

Topics: Adenosine Triphosphate; Animals; Blotting, Western; Cyclosporine; Cytochromes c; Cytosol; Energy Metabolism; Genetic Therapy; Green Fluorescent Proteins; Humans; Injections, Intravenous; Intercellular Signaling Peptides and Proteins; Liver; Liver Failure, Acute; Male; Membrane Potentials; Mice; Mice, Inbred BALB C; Mitochondria, Liver; Mitochondrial Swelling; Peptides; Permeability; Plasmids; Regional Blood Flow; Tail; Veins

This study examined the effects of genipin, isolated from Gardenia jasminoides Ellis, on d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic apoptosis and liver failure. Mice were given an intraperitoneal injection of genipin (25, 50, 100 and 200mg/kg) 1h before GalN (700mg/kg)/LPS (10microg/kg) administration. The survival rate of the genipin group was significantly higher than that of the control. Genipin markedly reduced the increases in serum aminotransferase activities and lipid peroxidation. The glutathione content decreased in GalN/LPS group, and this decrease was attenuated by genipin. Increases in serum tumor necrosis factor-alpha (TNF-alpha), which were observed in GalN/LPS-treated mice, were significantly reduced by genipin. Genipin attenuated the GalN/LPS-induced apoptosis of hepatocytes, as estimated by the caspase-3 and -8 activity assay, TNF-R1 associated death domain (TRADD) protein measurement and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method. Moreover, increased cytosolic cytochrome c protein was reduced by genipin. After 3h of GalN/LPS injection, nuclear phosphorylated c-Jun (p-c-Jun) level was significantly increased, whereas it was attenuated by genipin. Also, the increased nuclear level of nuclear factor-kappaB and the decreased cytosolic level of IkappaB-alpha protein were significantly attenuated by genipin. Our results suggest that genipin offers marked hepatoprotection against damage induced by GalN/LPS related with its antioxidative, anti-apoptotic activities, and inhibition of NF-kappaB nuclear translocation and nuclear p-c-Jun expression.

Topics: Animals; Apoptosis; Caspases; Cell Nucleus; Cytochromes c; Cytosol; Galactosamine; Gene Expression Regulation; Glutathione; I-kappa B Proteins; Iridoid Glycosides; Iridoids; Lipid Peroxidation; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Mice; Mice, Inbred ICR; NF-KappaB Inhibitor alpha; Oxidative Stress; Phosphorylation; Protein Transport; Proto-Oncogene Proteins c-jun; TNF Receptor-Associated Death Domain Protein; Transaminases; Transcription Factor RelA; Tumor Necrosis Factor-alpha

To find a novel drug against acute liver failure, a methionine derivative of bicyclol (WLP-S-10) was studied in acetaminophen-injected mice.. At first, 10 derivatives of bicyclol were tested in male KunMing strain mice injected with CCl(4), acetaminophen or d-galactosamine plus lipopolysaccharide (LPS), serum alanine aminotransferase (ALT) and mortality rate were determined. Among the 10 derivatives, a methionine derivative of bicyclol (WLP-S-10) was shown to be the most effective. A single dose of WLP-S-10 200 mg/kg was intraperitoneally injected 1 h before administration of a lethal dose of acetaminophen; the mortality rate, liver lesions, serum ALT, aspartate aminotransferase (AST) and liver glutathione (GSH) were determined. Mitochondrial GSH and adenosine triphosphate (ATP) levels, cytochrome C and apoptosis-inducing factor (AIF) leakage, mitochondrial swelling and membrane potential were determined.. As a result, WLP-S-10 200 mg/kg significantly reduced liver injury induced by CCl(4) and decreased the mortality rate of mice because of acute liver failure caused by lethal dosage of acetaminophen or d-galactosamine plus LPS. WLP-S-10 200 mg/kg markedly reduced liver necrosis, serum ALT and AST elevation and GSH depletion after injection of acetaminophen. WLP-S-10 inhibited mitochondrial swelling, breakdown of membrane potential and depletion of mitochondrial ATP, and also reduced release of cytochrome C and AIF from mitochondria induced by acetaminophen.. The results indicate that WLP-S-10 is a novel potential compound against acetaminophen-induced acute liver failure in mice, and its active mechanism is mainly related to protection against necrosis and apoptosis of hepatocytes through inhibition of mitochondrial energy (ATP) depletion and AIF and cytochrome C release.

Topics: Acetaminophen; Adenosine Triphosphate; Analgesics, Non-Narcotic; Animals; Apoptosis; Apoptosis Inducing Factor; Benzodioxoles; Biphenyl Compounds; Cytochromes c; Glutathione; Liver; Liver Failure, Acute; Male; Membrane Potential, Mitochondrial; Methionine; Mice; Mitochondria, Liver; Mitochondrial Swelling; Necrosis

To investigate the protective effect of stronger neo-minophafen C (SNMC) on fulminant hepatic failure (FHF) and its underlying mechanism.. A mouse model of FHF was established by intraperitoneal injection of galactosamine (D-Gal N) and lipopolysaccharide (LPS). The survival rate, liver function, inflammatory factor and liver pathological change were obtained with and without SNMC treatment. Hepatocyte survival was estimated by observing the stained mitochondria structure with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method and antibodies against cytochrome C (Cyt-C) and caspase-3.. The levels of plasma tumor necrosis factor alpha (TNF-alpha), nitric oxide (NO), ET-1, interleukin-6 (IL-6), and the degree of hepatic tissue injury were decreased in the SNMC-treated groups compared with those in the model group (P < 0.01). However, there were no differences after different dosages administered at different time points. There was a significant difference in survival rates between the SNMC-treated groups and the model group (P < 0.01). The apoptosis index was 32.3% at 6 h after a low dose of SNMC, which was considerably decreased from 32.3% +/- 4.7% vs 5% +/- 2.83% (P < 0.05) to 5% on d 7. The expression of Cyt-C and caspase-3 decreased with the prolongation of therapeutic time. Typical hepatocyte apoptosis was obviously ameliorated under electron microscope with the prolongation of therapeutic time.. SNMC can effectively protect liver against FHF induced by LPS/D-Gal N. SNMC can prevent hepatocyte apoptosis by inhibiting inflammatory reaction and stabilizing mitochondria membrane to suppress the release of Cyt-C and sequent activation of caspase-3.

Topics: Alanine Transaminase; Albumins; Animals; Apoptosis; Bilirubin; Caspase 3; Cysteine; Cytochromes c; Drug Combinations; Endothelin-1; Female; Glycine; Glycyrrhetinic Acid; Interleukin-6; Liver; Liver Failure, Acute; Mice; Microscopy, Electron; Tumor Necrosis Factor-alpha

TNFalpha is a pleiotropic cytokine that induces either cell proliferation or cell death. Inhibition of NF-kappaB activation increases susceptibility to TNFalpha-induced death, concurrent with sustained JNK activation, an important contributor to the death response. Sustained JNK activation in NF-kappaB-deficient cells was suggested to depend on reactive oxygen species (ROS), but how ROS affect JNK activation was unclear. We now show that TNFalpha-induced ROS, whose accumulation is suppressed by mitochondrial superoxide dismutase, cause oxidation and inhibition of JNK-inactivating phosphatases by converting their catalytic cysteine to sulfenic acid. This results in sustained JNK activation, which is required for cytochrome c release and caspase 3 cleavage, as well as necrotic cell death. Treatment of cells or experimental animals with an antioxidant prevents H(2)O(2) accumulation, JNK phosphatase oxidation, sustained JNK activity, and both forms of cell death. Antioxidant treatment also prevents TNFalpha-mediated fulminant liver failure without affecting liver regeneration.

Topics: Animals; Antioxidants; Caspase 3; Caspases; Cell Death; Chlorocebus aethiops; COS Cells; Cytochromes c; Enzyme Activation; HeLa Cells; Humans; Hydrogen Peroxide; JNK Mitogen-Activated Protein Kinases; Liver Failure, Acute; Mice; Mice, Knockout; Necrosis; Oxidation-Reduction; Oxidative Stress; Phosphoric Monoester Hydrolases; Reactive Oxygen Species; Sulfenic Acids; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Cytochrome c is known as a substance related to apoptosis. We investigated serum cytochrome c levels in patients with fulminant hepatitis (FH) compared with these levels in patients with acute or chronic liver diseases.. Serum cytochrome c was measured by an electrochemiluminescence immunoassay (ECLIA) method. The numbers of patients were as follows: fulminant hepatitis (FH; n = 15), acute hepatitis (AH; n = 12), chronic hepatitis (CH; n = 30), chronic hepatitis with acute aggravation (CHA; n = 6), liver cirrhosis (LC; n = 30), hepatocellular carcinoma (HCC; n = 30), and healthy volunteers (controls; n = 9).. The serum cytochrome c level in FH was 10 686 +/- 7787 pg/ml, with a significant difference (P < 0.01) compared to levels in the other groups. In the FH patients, the serum cytochrome c level was significantly correlated to serum mitochondria (m)-GOT, hepatocyte growth factor (HGF), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and alkaline phosphatase (ALP), and it was negatively correlated to serum alpha-fetoprotein (AFP), and total bilirubin (T.Bil.) The serum cytochrome c level seemed to parallel the severity of hepatic coma. Immunohistochemical study indicated TdT mediated dUTP nick end labeling (TUNEL)-positive cells in the livers of patients with FH.. These results suggest that serum cytochrome c may be a possible new marker for acute liver failure.

Topics: Adult; Aged; alpha-Fetoproteins; Aspartate Aminotransferases; Bilirubin; Biomarkers; Cytochromes c; Female; Hepatocyte Growth Factor; Hepatocytes; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Liver Failure, Acute; Male

Acute liver failure (ALF), characterized by massive hepatocyte necrosis, is often caused by drug poisoning, particularly with acetaminophen (APAP). Hepatocyte necrosis is consecutive to glutathione depletion by NAPQI, a metabolite of APAP, and to mitochondrial damages caused by reactive oxygen species (ROS) overproduction. Considering the structure of Mangafodipir, a contrast agent currently used in magnetic resonance imaging of the liver, we hypothesized that this molecule could exert an antioxidant activity and be possibly used as a treatment of APAP-induced ALF.. Mangafodipir is endowed with superoxide dismutase, catalase, and glutathione reductase activities. It can inhibit ROS production by hepatocytes in culture, and protect those cells from oxidative stresses induced by exposure to xanthine oxidase, H(2)O(2), or UV light. Moreover, preventive or curative administration of Mangafodipir to mice with APAP-induced ALF significantly increases survival rates, and abrogates aspartate aminotransferase elevation and histological damage.. Those data point out the potential interest of Mangafodipir in the treatment of toxic ALF in humans.

Topics: Acetaminophen; Animals; Antibodies, Monoclonal; Antioxidants; Carcinoma, Hepatocellular; Caspase 3; Caspase Inhibitors; Cell Line, Tumor; Cytochromes c; Edetic Acid; Enzymes; fas Receptor; Female; Glutathione; Humans; Liver; Liver Failure, Acute; Liver Neoplasms; Mice; Mice, Inbred BALB C; Oxidoreductases; Pyridoxal Phosphate; Reactive Oxygen Species; Superoxides; Survival Analysis