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Sample records for acute liver injury

  1. Acute alcohol-induced liver injury

    Gavin Edward Arteel

    2012-06-01

    Full Text Available Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, that also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.

  2. Acute liver injury induced by weight-loss herbal supplements

    Gary C Chen, Vivek S Ramanathan, David Law, Pauline Funchain, George C Chen, Samuel French, Boris Shlopov, Viktor Eysselein, David Chung, Sonya Reicher, Binh V Pham

    2010-01-01

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a caut...

  3. Montelukast induced acute hepatocellular liver injury

    Harugeri A

    2009-01-01

    Full Text Available A 46-year-old male with uncontrolled asthma on inhaled albuterol and formoterol with budesonide was commenced on montelukast. He developed abdominal pain and jaundice 48 days after initiating montelukast therapy. His liver tests showed an increase in serum total bilirubin, conjugated bilirubin, aspartate aminotranferase, alanine aminotranferase, and alkaline phosphatase. The patient was evaluated for possible non-drug related liver injury. Montelukast was discontinued suspecting montelukast induced hepatocellular liver injury. Liver tests began to improve and returned to normal 55 days after drug cessation. Causality of this adverse drug reaction by the Council for International Organizations of Medical Sciences or Roussel Uclaf Causality Assessment Method (CIOMS or RUCAM and Naranjo′s algorithm was ′probable′. Liver tests should be monitored in patients receiving montelukast and any early signs of liver injury should be investigated with a high index of suspicion for drug induced liver injury.

  4. Liver autophagy in anorexia nervosa and acute liver injury.

    Kheloufi, Marouane; Boulanger, Chantal M; Durand, François; Rautou, Pierre-Emmanuel

    2014-01-01

    Autophagy, a lysosomal catabolic pathway for long-lived proteins and damaged organelles, is crucial for cell homeostasis, and survival under stressful conditions. During starvation, autophagy is induced in numerous organisms ranging from yeast to mammals, and promotes survival by supplying nutrients and energy. In the early neonatal period, when transplacental nutrients supply is interrupted, starvation-induced autophagy is crucial for neonates' survival. In adult animals, autophagy provides amino acids and participates in glucose metabolism following starvation. In patients with anorexia nervosa, autophagy appears initially protective, allowing cells to copes with nutrient deprivation. However, when starvation is critically prolonged and when body mass index reaches 13 kg/m(2) or lower, acute liver insufficiency occurs with features of autophagic cell death, which can be observed by electron microscopy analysis of liver biopsy samples. In acetaminophen overdose, a classic cause of severe liver injury, autophagy is induced as a protective mechanism. Pharmacological enhancement of autophagy protects against acetaminophen-induced necrosis. Autophagy is also activated as a rescue mechanism in response to Efavirenz-induced mitochondrial dysfunction. However, Efavirenz overdose blocks autophagy leading to liver cell death. In conclusion, in acute liver injury, autophagy appears as a protective mechanism that can be however blocked or overwhelmed. PMID:25250330

  5. Liver Autophagy in Anorexia Nervosa and Acute Liver Injury

    Marouane Kheloufi

    2014-01-01

    Full Text Available Autophagy, a lysosomal catabolic pathway for long-lived proteins and damaged organelles, is crucial for cell homeostasis, and survival under stressful conditions. During starvation, autophagy is induced in numerous organisms ranging from yeast to mammals, and promotes survival by supplying nutrients and energy. In the early neonatal period, when transplacental nutrients supply is interrupted, starvation-induced autophagy is crucial for neonates’ survival. In adult animals, autophagy provides amino acids and participates in glucose metabolism following starvation. In patients with anorexia nervosa, autophagy appears initially protective, allowing cells to copes with nutrient deprivation. However, when starvation is critically prolonged and when body mass index reaches 13 kg/m2 or lower, acute liver insufficiency occurs with features of autophagic cell death, which can be observed by electron microscopy analysis of liver biopsy samples. In acetaminophen overdose, a classic cause of severe liver injury, autophagy is induced as a protective mechanism. Pharmacological enhancement of autophagy protects against acetaminophen-induced necrosis. Autophagy is also activated as a rescue mechanism in response to Efavirenz-induced mitochondrial dysfunction. However, Efavirenz overdose blocks autophagy leading to liver cell death. In conclusion, in acute liver injury, autophagy appears as a protective mechanism that can be however blocked or overwhelmed.

  6. Acute liver injury induced by weight-loss herbal supplements.

    Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

    2010-11-27

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss. PMID:21173910

  7. Acute liver failure and acute kidney injury: Definitions, prognosis, and outcome

    Włodzimirow, K.A.

    2013-01-01

    The objective of this thesis was to investigate definitions, prognostic indicators and their association with adverse events, mainly mortality for acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute kidney injury (AKI).

  8. Montelukast induced acute hepatocellular liver injury

    Harugeri A; Parthasarathi G; Sharma J; D′Souza G; Ramesh M

    2009-01-01

    A 46-year-old male with uncontrolled asthma on inhaled albuterol and formoterol with budesonide was commenced on montelukast. He developed abdominal pain and jaundice 48 days after initiating montelukast therapy. His liver tests showed an increase in serum total bilirubin, conjugated bilirubin, aspartate aminotranferase, alanine aminotranferase, and alkaline phosphatase. The patient was evaluated for possible non-drug related liver injury. Montelukast was discontinued suspecting montelukast i...

  9. Acetaminophen-induced acute liver injury in HCV transgenic mice

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  10. Acetaminophen-induced acute liver injury in HCV transgenic mice

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  11. Neutralization of ADAM8 ameliorates liver injury and accelerates liver repair in carbon tetrachloride-induced acute liver injury.

    Li, San-Qiang; Zhu, Sha; Wan, Xue-Dong; Xu, Zheng-Shun; Ma, Zhao

    2014-04-01

    Although some studies have described the function of ADAM8 (a disintegrin and metalloprotease 8) related with rheumatoid arthritis, cancer and asthma, etc., the concrete role of ADAM8 in acute liver injury is still unknown. So mice respectively received anti-ADAM8 monoclonal antibody (mAb) of 100 μg/100 μl, 200 μg/100 μl or 300 μg/100 μl in PBS or PBS pre-injection. Then acute liver injury was induced in the mice by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl₄). Serum AST and ALT level, Haematoxylin-eosin (H&E) staining, the expression level of vascular endothelial growth factor (VEGF), cytochrome P450 1A2 (CYP1A2) and proliferating cell nuclear antigen (PCNA) were detected in the mice after CCl4 administration. Our results showed that anti-ADAM8 mAb pre-injection could effectively lower AST and ALT levels (P < 0.05 or P < 0.01) and reduce liver injury (P < 0.05 or P <0.01), induce the expression of VEGF, CYP1A2 and PCNA (P <0.05 or P < 0.01) in dose-dependent manner compared with the control mice which received PBS pre-injection. In summary, our study suggested that ADAM8 might promote liver injury by inhibiting the proliferation of hepatocytes, angiogenesis and affecting the metabolism function of liver during acute liver injury induced by CCl₄. Anti-ADAM8 mAb injection might be suitable as a potential method for acute liver injury therapy. PMID:24646716

  12. Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation

    An Jiang; Chang Liu; Feng Liu; Yu-Long Song; Quan-Yuan Li; Liang Yu; Yi Lv

    2012-01-01

    AIM: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation. METHODS: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4  °C for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion. ...

  13. Modulation of the Colonic Bacterial Flora Affects Differently Bacterial Translocation and Liver Injury in an Acute Liver Injury Model

    Adawi, Diya; Molin, Göran; Ahrné, Siv; Jeppsson, Bengt

    2011-01-01

    Objective: To evaluate the effects of the administration of different bacterial strains on the extent of liver injury and bacterial translocation in an acute liver injury model. Design: Experimental study. Setting: University hospital, Sweden. Subjects: Sprague–Dawley rats. Interventions: Six different bacterial strains (Bacteroides fragilis ATCC 25285T, Enterococcus faecium No.1, Enterococcus faecium No.2, Escherichia coli F131, Lactobacillus plantarum DSM 6595, and Bifidobacterium lon...

  14. Serum acute phase reactants hallmark healthy individuals at risk for acetaminophen-induced liver injury

    Borlak, Jürgen; Chatterji, Bijon; Londhe, Kishor B; Watkins, Paul B

    2013-01-01

    Background Acetaminophen (APAP) is a commonly used analgesic. However, its use is associated with drug-induced liver injury (DILI). It is a prominent cause of acute liver failure, with APAP hepatotoxicity far exceeding other causes of acute liver failure in the United States. In order to improve its safe use this study aimed to identify individuals at risk for DILI prior to drug treatment by searching for non-genetic serum markers in healthy subjects susceptible to APAP-induced liver injury (...

  15. Protective mechanisms of garlic and wolfberry derivatives on acute and chronic liver injury animal models

    Xiao, Jia; 肖佳

    2012-01-01

    Liver is one of the most important organs in the body that maintains the homeostasis of metabolism, immunity, detoxification and hematopoiesis. A large number of acute and chronic intoxications and diseases can influence the normal functions of the liver, leading to irreversible liver damage and even cancer. Currently, applying herbs or herbal derivatives in the prevention and therapy of acute and chronic liver injury receive numerous attentions since they hold great potentials as food supple...

  16. Oroxylin A accelerates liver regeneration in CCl₄-induced acute liver injury mice.

    Runzhi Zhu

    Full Text Available INTRODUCTION: Based on the previous research that oroxylin A can suppress inflammation, we investigated the hepatoprotective role of oroxylin A against CCl₄-induced liver damage in mice and then studied the possible alteration of the activities of cytokine signaling participating in liver regeneration. Wild type (WT mice were orally administrated with oroxylin A (60 mg/kg for 4 days after CCl₄ injection, the anti-inflammatory effects of oroxylin A were assessed directly by hepatic histology and indirectly by measuring serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT and Albumin. Proliferating cell nuclear antigen (PCNA staining was performed to evaluate the role of oroxylin A in promoting hepatocyte proliferation. Serum IL-1β, TNF-α, IL-6 and IL-1Ra levels were measured by enzyme-linked immunosorbent assay (ELISA and liver HGF, EGF, TNF-α, IL-6, IL-1Ra and IL-1β gene expression was determined by quantitative real-time PCR. The data indicated that the IL-6 and TNF-α mRNA of oroxylin A administered group significantly increased higher than the control within 12 hours after CCl4 treatment. Meanwhile, oroxylin A significantly enhanced the expression of IL-1Ra at the early phase, which indicated that oroxylin A could facilitate the initiating events in liver regeneration by increasing IL-1Ra which acts as an Acute-Phase Protein (APP. In addition, a lethal CCl₄-induced acute liver failure model offers a survival benefit in oroxylin A treated WT mice. However, oroxylin A could not significantly improve the percent survival of IL-1RI⁻/⁻ mice with a lethal CCl₄-induced acute liver failure. CONCLUSIONS: Our study confirmed that oroxylin A could strongly promote liver structural remodeling and functional recovery through IL-1Ra/IL-1RI signaling pathway. All these results support the possibility of oroxylin A being a therapeutic candidate for acute liver injury.

  17. Increased plasma levels of microparticles expressing CD39 and CD133 in acute liver injury

    Schmelzle, Moritz; Splith, Katrin; Wiuff Andersen, Lars;

    2013-01-01

    BACKGROUND: We have previously demonstrated that CD133 and CD39 are expressed by hematopoietic stem cells (HSC), which are mobilized after liver injury and target sites of injury, limit vascular inflammation, and boost hepatic regeneration. Plasma microparticles (MP) expressing CD39 can block...... endothelial activation. Here, we tested whether CD133 MP might be shed in a CD39-dependent manner in a model of liver injury and could potentially serve as biomarkers of liver failure in the clinic. METHODS: Wild-type and Cd39-null mice were subjected to acetaminophen-induced liver injury. Mice were...... sacrificed and plasma MP were isolated by ultracentrifugation. HSC and CD133 MP levels were analyzed by fluorescence-activated cell sorting. Patients were enrolled with acute (n=5) and acute on chronic (n=5) liver injury with matched controls (n=7). Blood was collected at admission and plasma CD133 and CD39...

  18. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  19. Acute Hepatocellular Drug-Induced Liver Injury From Bupropion and Doxycycline

    Derek M Tang; Koh, Christopher; Twaddell, William S.; von Rosenvinge, Erik C; Han, Hyosun

    2015-01-01

    The management and diagnosis of drug-induced liver injury (DILI) is often challenging, particularly when patients are taking multiple medications. We present a 29-year-old African American man who presented with jaundice and malaise after starting bupropion and doxycycline 2 weeks prior. He was found to have acute hepatocellular drug-induced liver injury with autoimmune features, and made a complete recovery with prednisone. Although bupropion and doxycycline are both known to cause liver tox...

  20. Acute Hepatocellular Drug-Induced Liver Injury From Bupropion and Doxycycline.

    Tang, Derek M; Koh, Christopher; Twaddell, William S; von Rosenvinge, Erik C; Han, Hyosun

    2015-10-01

    The management and diagnosis of drug-induced liver injury (DILI) is often challenging, particularly when patients are taking multiple medications. We present a 29-year-old African American man who presented with jaundice and malaise after starting bupropion and doxycycline 2 weeks prior. He was found to have acute hepatocellular drug-induced liver injury with autoimmune features, and made a complete recovery with prednisone. Although bupropion and doxycycline are both known to cause liver toxicity, a closer inspection of the signature of liver injury and a review of prior related DILI cases assigns causality more to bupropion than doxycycline. PMID:26504884

  1. Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut.

    Araujo, James L; Worman, Howard J

    2015-01-01

    Despite the widespread use of herbal and dietary supplements (HDS), serious cases of hepatotoxicity have been reported. The popular herbal weight loss supplement, Hydroxycut, has previously been implicated in acute liver injury. Since its introduction, Hydroxycut has undergone successive transformations in its formulation; yet, cases of liver injury have remained an ongoing problem. We report a case of a 41-year-old Hispanic man who developed acute hepatocellular liver injury with associated nausea, vomiting, jaundice, fatigue and asterixis attributed to the use of a newer formulation of Hydroxycut, SX-7 Clean Sensory. The patient required hospitalisation and improved with supportive therapy. Despite successive transformations in its formulation, potential liver injury appears to remain an ongoing problem with Hydroxycut. Our case illustrates the importance of obtaining a thorough medication history, including HDS, regardless of new or reformulated product marketing efforts. PMID:25948859

  2. Acute liver injury with severe coagulopathy in marasmus caused by a somatic delusional disorder.

    Stein, Lance L; Jesudian, Arun B

    2011-01-01

    Marasmus is a severe form of protein-calorie malnutrition characterized by the depletion of fat stores, muscle wasting, and the lack of edema. In developed countries, marasmus is often the result of anorexia nervosa. Abnormal transaminases with liver synthetic dysfunction have rarely been reported with anorexia nervosa. To our knowledge, we report the first detailed case of acute liver injury with severe coagulopathy (INR > 1.5) in a patient with marasmus due to self-induced calorie restriction caused by a somatic delusional disorder. This case highlights the severity of liver injury that may occur with significant weight loss from self-induced calorie restriction and the rapid normalization of this injury with treatment. It is important for clinicians to be aware of patterns of acute liver injury in patients with severe protein-calorie malnutrition, regardless of the underlying cause. PMID:25954537

  3. Nrf2 activation prevents cadmium-induced acute liver injury

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H2DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice were

  4. Nrf2 activation prevents cadmium-induced acute liver injury

    Wu, Kai C. [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie J. [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

    2012-08-15

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice

  5. Total Flavonoids from Mimosa Pudica Protects Carbon Tetrachloride -Induced Acute Liver Injury in Mice

    Zhen-qin QIU

    2015-03-01

    Full Text Available Objective: To observe the protective effect of total flavonoids from Mimosa pudica on carbon tetrachloride (CCl4-induced acute liver injury in mice. Methods: CCl4-induced acute liver injury model in mice was established. The activity of ALT and AST, the content of serum albumin (Alb and total antioxidant capacity (T-AOC were determined. The content of malondiadehyde (MDA was measured and the activity of superoxide dismutase (SOD was determined. The histopathological changes of liver were observed.Results: Compared with CCl4 modle group, each dose group of total flavonouida from Mimosa pudica couldreduced the activity of ALT and AST in mice obviously (P<0.01, indicating they had remarkably protective effect on CCl4-induced acute liver injury in mice. high and middle dose groups of total flavonouida from Mimosa pudica couldincrease the content of Alb in mice (P<0.01. Each dose group of total flavonouida from Mimosa pudica could enhance the level of T-AOC (P<0.01. each dose group of total flavonouida from Mimosa pudica could lower the content of liver homogenate MDA but enhance the activity of SOD in a dose-depended manner (P<0.01. Conclusion: Total flavones from Mimosa Pudica have obvious protective effect on CCl4-induced acute liver injury in mice.

  6. Revisiting acute liver injury associated with herbalife products.

    Appelhans, Kristy; Smith, Casey; Bejar, Ezra; Henig, Y Steve

    2011-10-27

    In the November 27, 2010 issue of the World Journal of Hepatology (WJH), three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed as weight loss products. The reference to Herbalife products as contaminated and generally comparable to all dietary supplements or weight loss products is not scientifically supported. The authors provided an insufficient amount of information regarding patient histories, concomitant medications and other compounds, dechallenge results, and product specifications and usage. This information is necessary to fully assess the association of Herbalife products in the WJH case reports. Therefore, the article does not objectively support a causal relationship between the reported cases of liver injury and Herbalife products or ingredients. PMID:22059112

  7. Severe starvation-induced hepatocyte autophagy as a cause of acute liver injury in anorexia nervosa: a case report.

    Restellini, S; Spahr, L; Rubbia Brandt, L

    2013-01-01

    Introduction. Mild elevation of transaminase may be observed in anorexia nervosa, but acute liver injury is uncommon. A complex programmed cell death in response to starvation, called autophagy, has been described in experimental and human studies. Case Presentation. A 24-year-old woman suffering from anorexia nervosa was hospitalized for severe malnutrition. At admission, there were biological signs of acute liver injury but no electrolytic imbalance. After having ruled out the most common causes of liver injury, the patient was carefully refed. As liver tests remained abnormal, liver biopsy was performed. At histology and electron microscopy, numerous signs suggestive of starvation-induced hepatocyte autophagy were found. Discussion. Severe starvation can be associated with acute liver injury that is slowly reversible with careful enteral nutrition. In this clinical situation, profound hepatic glycogen depletion in association with autophagy appears as the leading cause of liver injury. PMID:25379300

  8. Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats

    B. Tang; Qiao, H.; Meng, F.; Sun, X.

    2007-01-01

    Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats...

  9. Genetic or Pharmacologic Amplification of Nrf2 Signaling Inhibits Acute Inflammatory Liver Injury in Mice

    Osburn, William O.; YATES, Melinda S.; Dolan, Patrick D.; Liby, Karen T.; Sporn, Michael B.; Taguchi, Keiko; Yamamoto, Masayuki; Kensler, Thomas W.

    2008-01-01

    Oxidative stress-mediated destruction of normal parenchymal cells during hepatic inflammatory responses contributes to the pathogenesis of immune-mediated hepatitis and is implicated in the progression of acute inflammatory liver injury to chronic inflammatory liver disease. The transcription factor NF-E2-related factor 2 (Nrf2) regulates the expression of a battery of antioxidative enzymes and Nrf2 signaling can be activated by small-molecule drugs that disrupt Keap1-mediated repression of N...

  10. Ascertainment of acute liver injury in two European primary care databases

    Ruigómez, A.; Brauer, R.; Rodríguez, L. A García; Huerta, C.; Requena, G.; Gil, M.; de Abajo, Francisco; Downey, G.; Bate, A.; Tepie, M. Feudjo; de Groot, M.C.H.; Schlienger, R.; Reynolds, R.; Klungel, O.

    2014-01-01

    Purpose The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI. Methods T

  11. Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury

    Ferguson, Michael A.; Vaidya, Vishal S.; Waikar, Sushrut S.; Collings, Fitz B.; Sunderland, Kelsey E.; Gioules, Costas J.; Bonventre, Joseph V.

    2009-01-01

    Acute kidney injury (AKI) is a common condition with significant associated morbidity and mortality. The insensitivity and non-specificity of traditional markers of renal dysfunction prevent timely diagnosis, estimation of the severity of renal injury, and the administration of possible therapeutic agents. Here, we determine the prognostic ability of urinary liver-type fatty acid-binding protein (L-FABP), and further characterize its sensitivity and specificity as a biomarker of AKI. Initial ...

  12. Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Kuur, E.C. van der; Morava, E.; Wevers, R A; Augustijn, K.D.; Touw, D.J.; Sandel, M.H.; Masereeuw, R.; Russel, F. G. M.

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw) followed by 24 h urine collection. Doses of >/=275 mg/kg bw APAP resulted in hepatic centrilobular...

  13. Identification of Novel Translational Urinary Biomarkers for Acetaminophen-Induced Acute Liver Injury Using Proteomic Profiling in Mice

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0–350 mg/kg bw) followed by 24 h urine collection. Doses of ≥275 mg/kg bw APAP resulted in hepatic centrilobular necr...

  14. CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure

    Stutchfield, Benjamin M.; Antoine, Daniel J.; Mackinnon, Alison C; Gow, Deborah J; Bain, Calum; Hawley, Catherine A.; Hughes, Michael J.; Francis, Benjamin; Wojtacha, Davina; Man, Tak Y.; Dear, James W.; Devey, Luke R.; Mowat, Alan; Pollard, Jeffrey W; Park, B Kevin

    2015-01-01

    Background & Aims: Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods: We measured levels of CSF1 in serum samples collected from 55 patients who underwent partia...

  15. Difficulties in diagnosing acute kidney injury post liver transplantation using serum creatinine based diagnostic criteria

    Banwari; Agarwal; Andrew; Davenport

    2014-01-01

    Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease(MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period.

  16. Dioscin alleviates dimethylnitrosamine-induced acute liver injury through regulating apoptosis, oxidative stress and inflammation.

    Zhang, Weixin; Yin, Lianhong; Tao, Xufeng; Xu, Lina; Zheng, Lingli; Han, Xu; Xu, Youwei; Wang, Changyuan; Peng, Jinyong

    2016-07-01

    In our previous study, the effects of dioscin against alcohol-, carbon tetrachloride- and acetaminophen-induced liver damage have been found. However, the activity of it against dimethylnitrosamine (DMN)-induced acute liver injury remained unknown. In the present study, dioscin markedly decreased serum ALT and AST levels, significantly increased the levels of SOD, GSH-Px, GSH, and decreased the levels of MDA, iNOS and NO. Mechanism study showed that dioscin significantly decreased the expression levels of IL-1β, IL-6, TNF-α, IκBα, p50 and p65 through regulating TLR4/MyD88 pathway to rehabilitate inflammation. In addition, dioscin markedly up-regulated the expression levels of SIRT1, HO-1, NQO1, GST and GCLM through increasing nuclear translocation of Nrf2 against oxidative stress. Furthermore, dioscin significantly decreased the expression levels of FasL, Fas, p53, Bak, Caspase-3/9, and upregulated Bcl-2 level through decreasing IRF9 level against apoptosis. In conclusion, dioscin showed protective effect against DMN-induced acute liver injury via ameliorating apoptosis, oxidative stress and inflammation, which should be developed as a new candidate for the treatment of acute liver injury in the future. PMID:27317992

  17. Involvement of immune-related factors in diclofenac-induced acute liver injury in mice

    Drug-induced liver injury (DILI) is a major safety concern in drug development and clinical drug therapy. However, the underlying mechanism of DILI is little known. It is difficult to predict DILI in humans due to the lack of experimental animal models. Diclofenac, a non-steroidal anti-inflammatory drug rarely causes severe liver injury in human, but there is some evidence for immunoallergic idiosyncratic reactions. In this study, the mechanism of diclofenac-induced liver injury in mice was investigated. First, we established the dosing condition for liver injury in normal mice. Plasma ALT and AST levels were significantly increased in diclofenac-administered (80 mg/kg, i.p.) mice in a dose- and time-dependent manner. Among several interleukins (ILs) and chemokines, mRNA expression of helper T (Th) 17 cell-mediated factors, such as retinoid orphan receptor (ROR)-γt, and signal transducers and activators of transcription factor (STAT) 3 in the liver, and the plasma IL-17 level were significantly increased. Neutralization of IL-17 tended to suppress the hepatotoxicity of diclofenac, suggesting that IL-17 was partly involved. Gadolinium chloride (GdCl3) administration demonstrated that Kupffer cells are not likely to be involved in diclofenac hepatotoxicity. Hepatic expressions of IL-1β mRNA and plasma IL-1β were significantly increased soon after the diclofenac administration. Then, the results of an in vivo neutralization study of IL-1β suggested that IL-1β was involved early in the time of pathogenesis of the diclofenac-induced liver injury. In conclusion, we firstly developed a diclofenac-induced acute liver injury model in normal mice, and the involvement of IL-17 and IL-1β was clarified.

  18. Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice

    Zhu, Run-Zhi; Xiang, Di; Xie, Chao; Li, Jing-Jing; Hu, Jian-Jun; He, Hong-Lin; Yuan, Yun-Sheng; GAO, JIN; HAN, WEI; Yu, Yan

    2010-01-01

    AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl4).

  19. MicroRNA-mediated Th2 bias in methimazole-induced acute liver injury in mice.

    Uematsu, Yasuaki; Akai, Sho; Tochitani, Tomoaki; Oda, Shingo; Yamada, Toru; Yokoi, Tsuyoshi

    2016-09-15

    MicroRNA (miRNA) is a class of small non-coding RNAs containing approximately 20 nucleotides that negatively regulate target gene expression. Little is known about the role of individual miRNAs and their targets in immune- and inflammation-related responses in drug-induced liver injury. In the present study, involvement of miRNAs in the T helper (Th) 2-type immune response was investigated using a methimazole (MTZ)-induced liver injury mouse model. Co-administration of L-buthionine-S,R-sulfoximine and MTZ induced acute hepatocellular necrosis and elevated plasma levels of alanine aminotransferase (ALT) from 4h onward in female Balb/c mice. The hepatic mRNA expression of Th2 promotive factors was significantly increased concomitantly with plasma ALT levels. In contrast, the hepatic mRNA expression of Th2 suppressive factors was significantly decreased during the early phase of liver injury. Comprehensive profiling of hepatic miRNA expression was analyzed before the onset of MTZ-induced liver injury. Using in silico prediction of miRNAs that possibly regulate Th2-related genes and subsequent quantification, we identified up-regulation of expression of miR-29b-1-5p and miR-449a-5p. Among targets of these miRNAs, down-regulation of Th2 suppressive transcription factors, such as SRY-related HMG-box 4 (SOX4) and lymphoid enhancer factor-1 (LEF1), were observed from the early phase of liver injury. In conclusion, negative regulation of the expression of SOX4 by miR-29b-1-5p and that of LEF1 by miR-449a-5p is suggested to play an important role in the development of Th2 bias in MTZ-induced liver injury. PMID:27421576

  20. Expression and significance of SOCS3 in liver tissue of rats with severe acute pancreatitis complicated by liver injury

    Wang, Bin; Zhang, Xiao-Hua; Miao-fan YANG; Xiao-wei WU; Xu, Xiao-Bing; Mei-xia GUO; Min-li LI

    2012-01-01

    Objective  To investigate the expression and mechanism of action of suppressor of cytokine signaling 3 (SOCS3) in liver tissue of rats with experimental severe acute pancreatitis (SAP) concurring with liver injury. Methods  The rat model of SAP was reproduced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. Thirty-two male SD rats were randomly assigned into 4 groups (8 each): normal control group (NC), SAP 6h, 12h, and 18h groups. The levels of serum amylase (...

  1.  Early initiation of MARS® dialysis in Amanita phalloides-induced acute liver injury prevents liver transplantation.

    Pillukat, Mike Hendrik; Schomacher, Tina; Baier, Peter; Gabriëls, Gert; Pavenstädt, Hermann; Schmidt, Hartmut H J

    2016-01-01

     Amanita phalloides is the most relevant mushroom intoxication leading to acute liver failure. The two principal groups of toxins, the amatoxins and the phallotoxins, are small oligopeptides highly resistant to chemical and physical influences. The amatoxins inhibit eukaryotic RNA polymerase II causing transcription arrest affecting mainly metabolically highly active cells like hepatocytes and renal cells. The clinically most characteristic symptom is a 6-40 h lag phase before onset of gastrointestinal symptoms and the rapid progression of acute liver failure leading to multi-organ failure and death within a week if left untreated. Extracorporeal albumin dialysis (ECAD) was reported to improve patient's outcome or facilitate bridging to transplantation. In our tertiary center, out of nine intoxicated individuals from five non-related families six patients presented with acute liver injury; all of them were treated with ECAD using the MARS® system. Four of them were listed on admission for high urgency liver transplantation. In addition to standard medical treatment for Amanita intoxication we initiated ECAD once patients were admitted to our center. Overall 16 dialysis sessions were performed. All patients survived with full native liver recovery without the need for transplantation. ECAD was well tolerated; no severe adverse events were reported during treatment. Coagulopathy resolved within days in all patients, and acute kidney injury in all but one individual. In conclusion, ECAD is highly effective in treating intoxication with Amanita phalloides. Based on these experiences we suggest early initiation and repeated sessions depending on response to ECAD with the chance of avoiding liver transplantation. PMID:27493118

  2. Severe Starvation-Induced Hepatocyte Autophagy as a Cause of Acute Liver Injury in Anorexia Nervosa: A Case Report

    Rubbia Brandt, L.; Spahr, L; S. Restellini

    2013-01-01

    Introduction. Mild elevation of transaminase may be observed in anorexia nervosa, but acute liver injury is uncommon. A complex programmed cell death in response to starvation, called autophagy, has been described in experimental and human studies. Case Presentation. A 24-year-old woman suffering from anorexia nervosa was hospitalized for severe malnutrition. At admission, there were biological signs of acute liver injury but no electrolytic imbalance. After having ruled out the most common c...

  3. Amelioration of liver injury by continuously targeted intervention against TNFRp55 in rats with acute-on-chronic liver failure.

    Yumin Xu

    Full Text Available BACKGROUND: Acute-on-chronic liver failure (ACLF is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor/TNFR (tumor necrosis factor receptor 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc] prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55 pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF. METHODOLOGY: Chronic liver disease (liver fibrosis/cirrhosis was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA, and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN/lipopolysaccharide (LPS i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations. PRINCIPAL FINDINGS: Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA. This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats. CONCLUSIONS: sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

  4. Influence of zinc sulfate intake on acute ethanol-induced liver injury in rats

    Sema Bolkent; Pelin Arda-Pirincci; Sehnaz Bolkent; Refiye Yanardag; Sevim Tunali; Sukriye Yildirim

    2006-01-01

    AIM: To investigate the role of metallothionein and proliferating cell nuclear antigen (PCNA) on the morphological and biochemical effects of zinc sulfate in ethanol-induced liver injury.METHODS: Wistar albino rats were divided into four groups. Group I; intact rats, group Ⅱ; control rats given only zinc, group Ⅲ; animals given absolute ethanol, group Ⅳ; rats given zinc and absolute ethanol.Ethanol-induced injury was produced by the 1 mL of absolute ethanol, administrated by gavage technique to each rat. Animals received 100 mg/kg per day zinc sulfate for 3 d 2 h prior to the administration of absolute ethanol.RESULTS: Increases in metallothionein immunoreactivity in control rats given only zinc and rats given zinc and ethanol were observed. PCNA immunohistochemistry showed that the number of PCNA-positive hepatocytes was increased significantly in the livers of rats administered ethanol + zinc sulfate. Acute ethanol exposure caused degenerative morphological changes in the liver. Blood glutathione levels decreased, serum alkaline phosphatase and aspartate transaminase activities increased in the ethanol group when compared to the control group. Liver glutathione levels were reduced, but lipid peroxidation increased in the livers of the group administered ethanol as compared to the other groups. Administration of zinc sulfate in the ethanol group caused a significant decrease in degenerative changes, lipid peroxidation, and alkaline phosphatase and aspartate transaminase activities, but an increase in liver glutathione.CONCLUSION: Zinc sulfate has a protective effect on ethanol-induced liver injury. In addition, cell proliferation may be related to the increase in metallothionein immunoreactivity in the livers of rats administered ethanol + zinc sulfate.

  5. BML-111 Protected LPS/D-GalN-Induced Acute Liver Injury in Rats.

    Yan, Dan; Liu, Hai-Ling; Yu, Zhong-Jian; Huang, Yong-Hong; Gao, Dian; Hao, Hua; Liao, Shou-Sheng; Xu, Fang-Yun; Zhou, Xiao-Yan

    2016-01-01

    Lipoxins (LXs) display unique pro-resolving and anti-inflammatory functions in a variety of inflammatory conditions. The present study was undertaken to investigate the effects of BML-111 (5(S),6(R),7-trihydroxyheptanoic acid methyl ester), the agonist of lipoxin A₄ receptor, in a model of Lipopolysaccharides (LPS) and d-Galactosamine (d-GalN) induced acute liver injury, and to explore the mechanisms. Histopathological analyses were carried out to quantify liver injury degree. The activities of myeloperoxidase (MPO) were examined to evaluate the levels of neutrophil infiltration. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were detected to evaluate the functions of the liver. The amounts of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA), and the expression levels of transforming growth factor-β1(TGF-β1) and cyclooxygenase-2 (COX-2) were examined using Western blotting. The antioxidant capacity, the activities of inducible nitric oxide synthase (iNOS), the contents of malondialdehyde (MDA) and nitric oxide (NO) were analyzed with the kits via biochemical analysis. We established the model of acute liver injury with lipopolysaccharide and d-Galactosamine (LPS/d-GalN): (1) histopathological results and MPO activities, with the activities of AST and ALT in serum, consistently demonstrated LPS and d-GalN challenge could cause severe liver damage, but BML-111 could prevent pathological changes, inhibit neutrophil infiltration, and improve the hepatic function; (2) LPS/d-GalN increased TNF-α, IL-1β, COX-2, and IL-10, while decreasing TGF-β1. However, BML-111 could repress LPS/d-GalN -induced TNF-α, IL-1β and COX-2, meanwhile increasing the expression levels of TGF-β1 and IL-10; (3) LPS/d-GalN inhibited the activities of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and hydroxyl

  6. BML-111 Protected LPS/D-GalN-Induced Acute Liver Injury in Rats

    Dan Yan

    2016-07-01

    Full Text Available Lipoxins (LXs display unique pro-resolving and anti-inflammatory functions in a variety of inflammatory conditions. The present study was undertaken to investigate the effects of BML-111 (5(S,6(R,7-trihydroxyheptanoic acid methyl ester, the agonist of lipoxin A4 receptor, in a model of Lipopolysaccharides (LPS and d-Galactosamine (d-GalN induced acute liver injury, and to explore the mechanisms. Histopathological analyses were carried out to quantify liver injury degree. The activities of myeloperoxidase (MPO were examined to evaluate the levels of neutrophil infiltration. The activities of aspartate aminotransferase (AST and alanine aminotransferase (ALT in serum were detected to evaluate the functions of the liver. The amounts of tumor necrosis factor-α (TNF-α, interleukin-10 (IL-10, and interleukin-1β (IL-1β were measured using enzyme-linked immunosorbent assay (ELISA, and the expression levels of transforming growth factor-β1(TGF-β1 and cyclooxygenase-2 (COX-2 were examined using Western blotting. The antioxidant capacity, the activities of inducible nitric oxide synthase (iNOS, the contents of malondialdehyde (MDA and nitric oxide (NO were analyzed with the kits via biochemical analysis. We established the model of acute liver injury with lipopolysaccharide and d-Galactosamine (LPS/d-GalN: (1 histopathological results and MPO activities, with the activities of AST and ALT in serum, consistently demonstrated LPS and d-GalN challenge could cause severe liver damage, but BML-111 could prevent pathological changes, inhibit neutrophil infiltration, and improve the hepatic function; (2 LPS/d-GalN increased TNF-α, IL-1β, COX-2, and IL-10, while decreasing TGF-β1. However, BML-111 could repress LPS/d-GalN -induced TNF-α, IL-1β and COX-2, meanwhile increasing the expression levels of TGF-β1 and IL-10; (3 LPS/d-GalN inhibited the activities of superoxide dismutase (SOD, catalase (CAT, total antioxidant capacity (T-AOC, and hydroxyl

  7. Up-regulated Reg proteins induced by Interleukin-22 treatment ameliorate acute liver injury in rat model

    Zhang, Hong-Bin; Luo, Hong-Chun; Xin, Xiao-Juan; Zeng, Ai-Zhong

    2015-01-01

    Background: The regenerating gene (Reg), encoding lectin-related protein, was originally isolated from a rat regenerating pancreatic islets. Interleukin-22 (IL-22), a recently identified cytokine, is produced by Th 17 cells and natural killer cells. Both of them have been shown to play an important role in controlling tissue repair. But, it is unclear whether the IL-22/Reg axis is involved in liver regeneration and the improvement of liver function in a rat model of acute liver injury. Aims: ...

  8. Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury

    Sun-Hee Jang

    2014-09-01

    Full Text Available Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP against hepatotoxicity induced by acute ethanol (EtOH intoxication in rats. Methods: Sprague-Dawley (SD rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW. The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14 and Taechung (LR3. A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST enzyme. It also significantly ameliorated the superoxide dismutase (SOD and the catalase (CAT activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol metabolizing enzymes and by attenuating oxidative stress.

  9. The protective or damaging effect of Tumor necrosis factor-α in acute liver injury is concentration-dependent

    Dong, Yulong; Liu, Yuzhou; Kou, Xingrui; Jing, Yingying; Sun, Kai; Sheng, Dandan; Yu, Guofeng; Yu, Dandan; Zhao, Qiudong; Zhao, Xue; Li, Rong; Wu, Mengchao; Wei, Lixin

    2016-01-01

    Background Inflammatory cytokine is important in modulating injured diseases. Tumor necrosis factor-α (TNF-α), one of potent inflammatory cytokines, plays a dominant role in host defense reaction. However, the concrete effect of TNF-α on acute liver injury is totally unclear. Here we reported the concrete effect and possible mechanisms of TNF-α on acute liver injury induced by carbon tetrachloride (CCl4). Methods SD male rats were equally divided into nine groups. CCl4 (1 ml/kg) was subcutane...

  10. Quantitative analysis of contrast-enhanced ultrasonography in acute radiation-induced liver injury: An animal model

    Feng, Jun; Chen, Shu-Bo; WU, SHU-JUN; Sun, Ping; XIN, TIAN-YOU; CHEN, YING-ZHEN

    2015-01-01

    The aim of the present study was to examine and assess contrast-enhanced ultrasound in the early diagnosis of acute radiation-induced liver injury in a rat model. Sixty female rats were used, with 50 rats being utilized to produce an animal model of liver injury with a single dose of stereotactic X-ray irradiation of 20 Gy. Ten rats from the injury group and 2 rats from the control group were randomly selected on days 3, 7, 14, 21 and 28, and examined by contrast-enhanced ultrasound and histo...

  11. Protective effect of wedelolactone against CCl4-induced acute liver injury in mice.

    Lu, Yang; Hu, DongMei; Ma, ShanBo; Zhao, Xian; Wang, Shan; Wei, Guo; Wang, XiFang; Wen, AiDong; Wang, JingWen

    2016-05-01

    Eclipta, a traditional Chinese medicine, has been used to treat liver disease for centuries. However, the chemical basis and biological mechanisms of Eclipta remain elusive. The current study aims to investigate the hepatoprotective effect of wedelolactone (WEL), a major coumarin in Eclipta, using C57BL/6 mice with carbon tetrachloride CCl4-induced acute liver injury (ALI). Our data showed that WEL markedly decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and improved hepatic histopathology changes. WEL also significantly decreased the content of MDA in liver tissues, meanwhile increased the activities of antioxidant enzymes SOD and GSH-Px. In addition, WEL reduced the protein expression of TNF-α, IL-1β and IL-6, as well as mRNA expression. Western blot results revealed that WEL repressed phosphorylation of extracellular signal-regulated kinase (ERK) and translocation of NF-κB p65 from cytoplasm to nucleus and enhanced the phosphorylation of c-Jun. N-terminal kinase (JNK). Moreover, results showed that WEL significantly inhibited CCl4-induced hepatocytes apoptosis, markedly suppressed the down-regulation of Bax and active Caspase-3 expression and accelerated the expression of Bcl-2. Overall, the findings indicate that WEL exhibits a protective effect against CCl4-induced ALI in mice by enhancing the antioxidative defense system, suppressing the inflammatory response and cell apoptosis of liver. PMID:26921731

  12. Protective effect of recombinant human IL-1Ra on CCl_4-induced acute liver injury in mice

    2010-01-01

    AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl 4 ). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl 4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl 4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneo...

  13. Down-regulation of miR-192-5p protects from oxidative stress-induced acute liver injury.

    Roy, Sanchari; Benz, Fabian; Alder, Jan; Bantel, Heike; Janssen, Joern; Vucur, Mihael; Gautheron, Jeremie; Schneider, Anne; Schüller, Florian; Loosen, Sven; Luedde, Mark; Koch, Alexander; Tacke, Frank; Luedde, Tom; Trautwein, Christian; Roderburg, Christoph

    2016-07-01

    miR-192-5p has gained increasing relevance in various diseases, however, its function in acute liver injury is currently unknown. We analysed miR-192-5p serum levels and hepatic miR-192-5p expression in mice after hepatic ischaemia and reperfusion (I/R) as well as in toxic liver injury. On a functional level, miRNA levels were analysed in the different hepatic cell-compartments and in the context of tumour necrosis factor (TNF)-dependent liver cell death. We detected increased serum levels of miR-192-5p after hepatic I/R- and carbon tetrachloride (CCl4)-induced liver injury. miR-192-5p levels correlated with the degree of liver damage and the presence of hepatic cell death detected by TUNEL stainings (terminal deoxynucleotidyltransferase-mediated dUTP biotin nick-end labelling stainings). Moreover, expression of miR-192-5p was increased in a hypoxia/reoxygenation (H/R) model of in vitro hepatocyte injury, supporting that the passive release of miR-192-5p represents a surrogate for hepatocyte death in liver injury. In critically ill patients, miR-192-5p levels were elevated selectively in patients with liver injury and closely correlated with the presence of hepatic injury. In contrast with up-regulated miR-192-5p in the serum, we detected a down-regulation of miR-192-5p in both injured mouse and human livers. Deregulation of miR-192-5p in livers was dependent on stimulation with TNF. Functional experiments confirmed a protective effect of down-regulation of miR-192-5p in hepatocytes, suggesting a role of miR-192-5p in limiting liver injury. Finally, we identified Zeb2, an important regulator of cell death, as a potential target gene mediating the function of miR-192-5p Our data suggest that miR-192-5p is involved in the regulation of liver cell death during acute liver injury and might represent a potent marker of hepatic injury. PMID:27129188

  14. Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats

    B. Tang

    2007-12-01

    Full Text Available Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats were injected intravenously with lipopolysaccharide (LPS 24 h after 70% hepatectomy. Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls. Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times (6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection, compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-a, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS. In summary, glycyrrhizin may represent a potent drug protecting the liver against endotoxin-induced injury, especially after massive hepatectomy.

  15. Application of interleukin-22 mediates protection in experimental acetaminophen-induced acute liver injury.

    Scheiermann, Patrick; Bachmann, Malte; Goren, Itamar; Zwissler, Bernhard; Pfeilschifter, Josef; Mühl, Heiko

    2013-04-01

    Acetaminophen (APAP, paracetamol)-induced hepatotoxicity, although treatable by timely application of N-acetylcysteine, can be fatal. Because it is among the common causes of acute liver failure in intensive care units and in light of its gradually increasing incidence, the need for novel therapeutic strategies aimed at severe intoxication is apparent. Recently, it has been shown that IL-22, a STAT3-activating cytokine, has the capability to mediate liver protection. Herein, the protective potential of IL-22 in murine APAP-induced hepatotoxicity was assessed. Intravenous administration of prophylactic IL-22 significantly reduced serum alanine aminotransferase levels and histopathologic damage in APAP-induced liver injury, a process that coincided with increased hepatocyte proliferation in vivo. Concomitant gene expression analysis revealed hepatic induction of genes prototypically up-regulated by the IL-22/STAT3 axis, among others suppressor of cytokine signaling-3, lipocalin-2, and α1-antichymotrypsin. Notably, in a translational setting of therapeutic treatment 2 hours after APAP, IL-22 supported protection in the context of suboptimal N-acetylcysteine dosing. IL-22 likewise connected to augmented hepatocyte proliferation in this experimental setting. As detected by analysis of inflammatory cytokine production, systemically applied IL-22 did not display acute immunomodulation/stimulation in otherwise untreated or endotoxemic mice. Those latter observations clearly confirm acute tolerability of systemically applied IL-22. Observations presented altogether suggest that therapeutic IL-22 administration is a conceivable tissue-protective regimen aimed at hard-to-treat patients with severe APAP-induced hepatotoxicity. PMID:23375450

  16. Protective mechanisms of wogonoside against Lipopolysaccharide/D-galactosamine-induced acute liver injury in mice.

    Gao, Yuan-Zheng; Zhao, Lian-Feng; Ma, Jun; Xue, Wei-Hong; Zhao, Hui

    2016-06-01

    Wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Georgi, has been reported to have anti-inflammatory and antioxidant effects. In this study, we examined the protective effects of wogonoside against lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced liver injury in mice. Mice were given an intraperitoneal injection of wogonoside 1h before LPS and d-GalN treatment. The results showed that wogonoside inhibited the production of serum Alanine transaminase (ALT), Aspartate aminotransferase (AST), IL-1β, TNF-α, and hepatic malondialdehyde (MDA) content induced by LPS/GalN. In addition, wogonoside promoted the expression of Nrf2, NQO-1, GCLC, and HO-1. Wogonoside inhibited the expression of hepatic NLRP3, ASC, caspase-1, and IL-1β induced by LPS/GalN. In conclusion, these results suggest that wogonoside protects against LPS/GalN-induced acute liver injury by activating Nrf2 and inhibiting NLRP3 inflammasome activation. PMID:26921756

  17. Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury

    Xie, Jieshi; Yang, Le; Tian, Lei; Li, Weiyang; Yang, Lin; Li, Liying

    2016-01-01

    Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation. PMID:27273604

  18. Effects of Shark Hepatic Stimulator Substance on the Function and Antioxidant Capacity of Liver Mitochondria in an Animal Model of Acute Liver Injury

    Qiu-Ling FAN; Cai-Guo HUANG; Yan JIN; Bo FENG; Hui-Nan MIAO; Wen-Jie LI; Bing-Hua JIAO; Qin-Sheng YUAN

    2005-01-01

    This study was carried out to investigate whether shark hepatic stimulator substance (HSS) can prevent acute liver injury and affect mitochondrial function and antioxidant defenses in a rat model of thioacetamide (TAA)-induced liver injury. The acute liver injury was induced by two intraperitoneal injections of TAA (400 mg/kg) in a 24 h interval. In the TAA plus shark HSS group, rats were treated with shark HSS (80 mg/kg) 1 h prior to each TAA injection. In this group, serum liver enzyme activities were significantly lower than those in the TAA group. The mitochondrial respiratory control ratio was improved, and the mitochondrial respiratory enzyme activities were increased in the TAA plus shark HSS group. The mitochondrial antioxidant enzyme activities and glutathione level were higher in the TAA plus shark HSS group than in the TAA group. These results suggest that the protective effect of shark HSS against TAA-induced acute liver injury may be a result of the restoration of the mitochondrial respiratory function and antioxidant defenses and decreased oxygen stress.

  19. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

    Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E;

    2010-01-01

    Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and....../or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally and......(6266) (p <0.05), and stationary levels for Aqp1. Aqp1 and Aqp4 mRNA were stationary. This study indicates that Aqp4, but not Aqp1, may be of importance in the pathogenesis of cortical brain edema in mice with ALF....

  20. Senescence marker protein 30 (SMP30)/regucalcin (RGN) expression decreases with aging, acute liver injuries and tumors in zebrafish

    Highlights: → Zebrafish SMP30/RGN mRNA expression decreases with aging. → Decreased expression was observed in liver tumors as compared to the surrounding area. → SMP30/RGN is important for liver proliferation and tumorigenesis. -- Abstract: Senescence marker protein 30 (SMP30)/regucalcin (RGN) is known to be related to aging, hepatocyte proliferation and tumorigenesis. However, expression and function of non-mammalian SMP30/RGN is poorly understood. We found that zebrafish SMP30/RGN mRNA expression decreases with aging, partial hepatectomy and thioacetamide-induced acute liver injury. SMP30/RGN expression was also greatly decreased in a zebrafish liver cell line. In addition, we induced liver tumors in adult zebrafish by administering diethylnitrosamine. Decreased expression was observed in foci, hepatocellular carcinomas, cholangiocellular carcinomas and mixed tumors as compared to the surrounding area. We thus showed the importance of SMP30/RGN in liver proliferation and tumorigenesis.

  1. Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series

    Castellote José

    2011-07-01

    Full Text Available Abstract Background Acute liver injury (ALI induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug. The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case. Methods Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol. Results In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8 and of 10 per million paracetamol users-year (95% CI 4.3-19.4. Conclusions Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.

  2. Systematic Review and Meta-Analysis: Macrolides- and Amoxicillin/Clavulanate-induced Acute Liver Injury.

    Ferrer, Pili; Amelio, Justyna; Ballarín, Elena; Sabaté, Mònica; Vidal, Xavi; Rottenkolber, Marietta; Schmiedl, Sven; Laporte, Joan-Ramon; Ibáñez, Luisa

    2016-07-01

    Antibacterials are frequently associated with idiosyncratic drug-induced liver injury (DILI). The objective of this study was to estimate the risk of macrolides and amoxicillin/clavulanate (AMC) on DILI. We conducted a systematic review (SR) and meta-analysis (MA) with studies retrieved from PubMed, Cochrane Library Plus, Web of Knowledge, clinicaltrials.gov, Livertox and Toxline (1980-2014). We searched for macrolides, AMC and MeSH and synonym terms for DILI. We included all study designs except case reports/series, all population ages and studies with a placebo/non-user comparator. We summarized the evidence with a random-effects MA. Quality of the studies was appraised with a checklist developed for SR of adverse effects. Heterogeneity and publication bias were assessed with different exploratory tools. We finally included 10 (two randomized clinical trials, six case-control, one cohort and one case-population studies) and 9 (case-population excluded) articles in the SR and MA, respectively. The overall summary relative risk of DILI for macrolides was 2.85 [95% confidence interval (CI) 1.81-4.47], p studies were perceived to be missing in the area of low statistical significance. Year of study and selected exposure window partly explained the variability between studies. For AMC, the risk of DILI was 9.38 (95% CI 0.65-135.41) p = 0.3, I2 = 95%. In conclusion, although spontaneous reports and case series have long established an association between macrolides and AMC with acute liver injury, these SR and MA have assessed the magnitude of this association. The low incidence of DILI and the therapeutic place of these antibiotics might tilt the balance in favour of their benefits. PMID:26707367

  3. Icaritin ameliorates carbon tetrachloride-induced acute liver injury mainly because of the antioxidative function through estrogen-like effects.

    Liu, Peng; Jin, Xiang; Lv, Hao; Li, Jing; Xu, Wen; Qian, Hai-hua; Yin, Zhengfeng

    2014-12-01

    To investigate the effects of icaritin, an active ingredient extracted from Epimedium Sagittatum (Sieb. et Zucc.), on CCl4-induced liver injury and its possible mechanisms. Hepatocytes isolated from Sprague-Dawley male rats were treated with 3 mmol/L CCl4 for 24 h to induce acute liver cell injury, then icaritin (0.1, 1, 10, 100 μmol/L, respectively) was administrated to the cells, and estrogen receptor antagonist ICI182,780 (1 μmol/L) was co-treated with 10 μmol/L icaritin. Biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD)) and cell apoptosis were detected to evaluate the injury degree. Protein expressions of Bax, Bcl-2, liver fatty acid-binding protein (L-FABP), and peroxisome proliferator-activated receptor-α (PPAR-α) as well as reactive oxygen species (ROS) generation were determined by western blot. Icaritin alleviated CCl4-induced liver cell injury in a concentration-dependent manner and 10 μmol/L was the optimal concentration. Icaritin (10 μmol/L) significantly reduced activities of ALT, AST in cell culture medium and MDA level of the impaired liver cells, but increased the intercellular SOD activity. The apoptotic rate of the impaired liver cells was also decreased by icaritin (10 μmol/L) treatment. Icaritin might exert antioxidative and anti-apoptotic functions via estrogen-like effect, as the ratio of Bcl-2/Bax was significantly increased, while protein expressions of L-FABP and PPAR-α were markedly increased, and this function was blocked by the estrogen receptor antagonist ICI182,780 efficiently. Icaritin may be a promising drug candidate for acute liver injury benefiting from the antioxidative and anti-apoptotic functions via estrogen-like effect. PMID:25148823

  4. Ethanol extracts of Scutellaria baicalensis protect against lipopolysaccharide-induced acute liver injury in mice

    Hai Nguyen Thanh; Hue Pham Thi Minh; Tuan Anh Le; Huong Duong Thi Ly; Tung Nguyen Huu; Loi Vu Duc; Thu Dang Kim; Tung Bui Thanh

    2015-01-01

    To investigated the protective potential of ethanol extracts of Scutellaria baicalensis (S. baicalensis ) against lipopolysaccharide (LPS)-induced liver injury. Methods: Dried roots of S. baicalensis were extracted with ethanol and concentrated to yield a dry residue. Mice were administered 200 mg/kg of the ethanol extracts orally once daily for one week. Animals were subsequently administered a single dose of LPS (5 mg/kg of body weight, intraperitoneal injection). Both protein and mRNA levels of cytokines, such as tumor necrosis factor alpha, interleukin-1β, and interleukin-6 in liver tissues were evaluated by ELISA assay and quantitative PCR. Cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB protein levels in liver tissues were analyzed by western blotting. Results: Liver injury induced by LPS significantly increased necrosis factor alpha, interleukin-1β, interleukin-6, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor-κB in liver tissues. Treatment with ethanol extracts of S. baicalensis prevented all of these observed changes associated with LPS-induced injury in liver mice. Conclusions: Our study showed that S. baicalensis is potentially protective against LPS-induced liver injury in mice.

  5. Kupffer cell-mediated exacerbation of methimazole-induced acute liver injury in rats.

    Akai, Sho; Uematsu, Yasuaki; Tsuneyama, Koichi; Oda, Shingo; Yokoi, Tsuyoshi

    2016-05-01

    Methimazole (MTZ), an anti-thyroid drug, is known to cause liver injury in humans. It has been demonstrated that MTZ-induced liver injury in Balb/c mice is accompanied by T helper (Th) 2 cytokine-mediated immune responses; however, there is little evidence for immune responses associated with MTZ-induced liver injury in rats. To investigate species differences in MTZ-induced liver injury, we administered MTZ with a glutathione biosynthesis inhibitor, L-buthionine-S,R-sulfoximine (BSO), to F344 rats and subsequently observed an increase in plasma alanine aminotransferase (ALT) and high-mobility group box 1 (HMGB1), which are associated with hepatic lesions. The hepatic mRNA expression of innate immune-related genes significantly increased in BSO- and MTZ-treated rats, but the change in Th2-related genes was not much greater than the change observed in the previous mouse study. Moreover, an increase in Kupffer cells and an induction of the phosphorylation of extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) proteins were accompanied by an increase in Toll-like receptor 4 (TLR4) expression, indicating that Kupffer cell activation occurs through HMGB1-TLR4 signaling. To elucidate the mechanism of liver injury in rats, gadolinium chloride, which inactivates the function of Kupffer cells, was administered before BSO and MTZ administration. The gadolinium chloride treatment significantly suppressed the increased ALT, which was accompanied by decreased hepatic mRNA expression related to innate immune responses and ERK/JNK phosphorylation. In conclusion, Kupffer cell-mediated immune responses are crucial factors for the exacerbation of MTZ-induced liver injury in rats, indicating apparent species differences in the immune-mediated exacerbation of liver injury between mice and rats. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26177832

  6. Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling

    Lee Hsuan-Shu; Yu Chia-Jung; Chen Wang-Chuan; Lin Bor-Ru; Chang Huei-Min; Lee Yen-Chih; Chien Chiang-Ting; Chen Chau-Fong

    2009-01-01

    Abstract Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI). The present study was undertaken to determine whether D-galactosamine (D-GalN) induces ALI via the mitochondrial apoptosis- and proinflammatory cytokine-signaling pathways, and possible mechanism(s) by which green tea (GT) extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS) production f...

  7. Effects of recombinant human growth hormone on acute liver injury induced by enterogenic endotoxemia in rats

    Ying LIN

    2011-02-01

    Full Text Available Objective To investigate the effects of recombinant human growth hormone(rh-GH on acute liver injury induced by enterogenic endotoxemia in rats.Methods Sixty rats were randomly assigned into three groups(20 each: normal control group(NC group,intestinal obstruction and ischemia group(IOI group and growth hormone group(GH group.Each group was divided again into two subgroups(10 each according to different time intervals.The ileum and the mesenteric vessels were ligated to reproduce the IOI rat model(IOI group.rh-GH [2.25U/(kg d,i.m] was given to the IOI rats in GH group.The mean arterial blood pressure(MAP,alanine transaminase(ALT and total bilirubin(TBIL were measured at the 36th and 72nd hour after treatment.The level of endotoxin,tumor necrosis factor α(TNF-α and interleukin-1β(IL-1β in plasma were determined by limulus test and ELISA.The histopathological changes of the liver were observed at each time interval.Results Compared with NC group,MAP decreased markedly in IOI group at different time points(P < 0.05,while no obvious changes were found in GH group.The concentration of endotoxin in plasma was much higher in IOI group than in NC group at each time point,while increased only at the 36th hour after treatment in GH group(P < 0.05.The concentrations of TNF-α,IL-1β,ALT and TBIL in plasma were significantly increased in IOI and GH group than in NC group at each time point,while decreased in GH group compared with that in IOI group(P < 0.05.The histopathological changes in liver were obviously ameliorated in GH group than in IOI group at each time point.Conclusions rh-GH may obviously improve the function and histopathological changes in livers in IETM rats,and the results may be attributed to its function of ameliorating the severity of septic shock and reducing the endotoxin and inflammatory cytokines levels in plasma.

  8. Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice.

    van Swelm, Rachel P L; Laarakkers, Coby M M; van der Kuur, Ellen C; Morava-Kozicz, Eva; Wevers, Ron A; Augustijn, Kevin D; Touw, Daan J; Sandel, Maro H; Masereeuw, Rosalinde; Russel, Frans G M

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw) followed by 24 h urine collection. Doses of ≥275 mg/kg bw APAP resulted in hepatic centrilobular necrosis and significantly elevated plasma alanine aminotransferase (ALT) values (pintoxication the presence of SOD1 and CA3, whereas both proteins were absent in control urine samples. Urinary concentrations of CaM were significantly increased and correlated well with plasma APAP concentrations (r = 0.97; p<0.0001) in human APAP intoxicants, who did not present with elevated plasma ALT levels. In conclusion, using this urinary proteomics approach we demonstrate CA3, SOD1 and, most importantly, CaM as potential human biomarkers for APAP-induced liver injury. PMID:23166697

  9. Preventive Effects of Dexmedetomidine on the Liver in a Rat Model of Acid-Induced Acute Lung Injury

    Velat Şen

    2014-01-01

    Full Text Available The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300–350 g were allocated randomly to four groups. In group 1, normal saline (NS was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI was found to be associated with increased malondialdehyde (MDA, total oxidant activity (TOA, oxidative stress index (OSI, and decreased total antioxidant capacity (TAC. Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P<0.05. The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

  10. Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

    Sen, Velat; Güzel, Abdulmenap; Şen, Hadice Selimoğlu; Ece, Aydın; Uluca, Unal; Söker, Sevda; Doğan, Erdal; Kaplan, İbrahim; Deveci, Engin

    2014-01-01

    The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300-350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI. PMID:25165710

  11. Severe Aplastic Anemia following Acute Hepatitis from Toxic Liver Injury: Literature Review and Case Report of a Successful Outcome

    Kamran Qureshi

    2014-01-01

    Full Text Available Hepatitis associated aplastic anemia (HAAA is a rare syndrome in which severe aplastic anemia (SAA complicates the recovery of acute hepatitis (AH. HAAA is described to occur with AH caused by viral infections and also with idiopathic cases of AH and no clear etiology of liver injury. Clinically, AH can be mild to fulminant and transient to persistent and precedes the onset SAA. It is assumed that immunologic dysregulation following AH leads to the development of SAA. Several observations have been made to elucidate the immune mediated injury mechanisms, ensuing from liver injury and progressing to trigger bone marrow failure with the involvement of activated lymphocytes and severe T-cell imbalance. HAAA has a very poor outcome and often requires bone marrow transplant (BMT. The findings of immune related myeloid injury implied the use of immunosuppressive therapy (IST and led to improved survival from HAAA. We report a case of young male who presented with AH resulting from the intake of muscle building protein supplements and anabolic steroids. The liver injury slowly resolved with supportive care and after 4 months of attack of AH, he developed SAA. He was treated with IST with successful outcome without the need for a BMT.

  12. Pathological changes in the liver after allogeneic bone marrow stromal cells transplantation via percutaneous needle injection in patients with acute liver injury

    Objective: To observe the histopathological changes in the liver after transplanting allogeneic bone marrow stromal cells (BMSCs) into liver of acute liver injury (ALI) via percutaneous needle injection. Methods: BMSCs were derived from bone marrow obtained from femoral and tibial bones of male albino rabbits BMSCs were separated, grown, and propagated in culture for 3 weeks 58 syngeneic male rabbits were reduced liver injury with D-galactosamine 24 hours later. 5 mL (about 2×107 cell/mL) BMSCs or D-hanks solution were percutaneously injected into livers of BMSCs group (n=24) and control group (D-hanks solution group, n=34) respectively. The rabbits were killed at different time points (1 week, 2 week, 4 week) Histopathological changes and degrees of necrosis in the hepatic tissues were assessed by two histopathologists blinded to treated group and each other's results. Results: The degree of liver necrosis was decreased and the proliferation of hepatocytes was significantly stimulated in the BMSCs group compared to the D-hanks group; the histopathological scores of the 2 groups were statistically significant (P<0.001). Conclusion: The transplantation of BMSCs have a significant anti-injurious ability. (authors)

  13. Hepatoprotective Effect of Terminalia chebula against t-BHP-Induced Acute Liver Injury in C57/BL6 Mice

    Choi, Min-Kyung; Kim, Hyeong-Geug; Han, Jong-Min; Lee, Jin-Seok; Lee, Jong Suk; Chung, Sun Ho; Son, Chang-Gue

    2015-01-01

    We aimed to identify the hepatoprotective effects of Terminalia chebula water extract (TCW) and its corresponding pharmacological actions using C57/BL6 mice model of tert-butylhydroperoxide-(t-BHP-) induced acute liver injury. Mice were orally administered with TCW (0, 50, 100, or 200 mg/kg) or gallic acid (100 mg/kg) for 5 days before t-BHP (2.5 mM/kg) injection. Liver enzymes, histopathology, oxidative stress parameters, antioxidant components, and inflammatory cytokines were examined 18 h after t-BHP injection. t-BHP injection caused dramatic elevation of serum AST, ALT, and LDH level, while TCW pretreatment notably attenuated these elevations. Inflammatory cytokines including TNF-α, IL-1β, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. t-BHP injection notably increased malondialdehyde, total reactive oxygen species, and nitric oxide in the liver tissue, while it markedly dropped the antioxidant activities including total antioxidant capacity, total glutathione contents, glutathione peroxidase, superoxide dismutase, and catalase. TCW pretreatment remarkably ameliorated these alterations, and these effects were relevant to gene expressions. Histopathological examinations supported the above findings. Collectively, these findings well prove that TCW beneficially prevents acute and severe liver injury and clarify its corresponding mechanisms involved in the inhibition of oxidative stress and inflammatory cytokines. PMID:25691908

  14. Hepatoprotective Effect of Terminalia chebula against t-BHP-Induced Acute Liver Injury in C57/BL6 Mice

    Min-Kyung Choi

    2015-01-01

    Full Text Available We aimed to identify the hepatoprotective effects of Terminalia chebula water extract (TCW and its corresponding pharmacological actions using C57/BL6 mice model of tert-butylhydroperoxide-(t-BHP- induced acute liver injury. Mice were orally administered with TCW (0, 50, 100, or 200 mg/kg or gallic acid (100 mg/kg for 5 days before t-BHP (2.5 mM/kg injection. Liver enzymes, histopathology, oxidative stress parameters, antioxidant components, and inflammatory cytokines were examined 18 h after t-BHP injection. t-BHP injection caused dramatic elevation of serum AST, ALT, and LDH level, while TCW pretreatment notably attenuated these elevations. Inflammatory cytokines including TNF-α, IL-1β, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. t-BHP injection notably increased malondialdehyde, total reactive oxygen species, and nitric oxide in the liver tissue, while it markedly dropped the antioxidant activities including total antioxidant capacity, total glutathione contents, glutathione peroxidase, superoxide dismutase, and catalase. TCW pretreatment remarkably ameliorated these alterations, and these effects were relevant to gene expressions. Histopathological examinations supported the above findings. Collectively, these findings well prove that TCW beneficially prevents acute and severe liver injury and clarify its corresponding mechanisms involved in the inhibition of oxidative stress and inflammatory cytokines.

  15. Evaluation of acute hepatic injury using 99mTc-Lactosylated serum albumin liver scintigraphy in rats treated with dimethylnitrosamine

    Objective: To assess the feasibility of hepatic asialoglycoprotein receptor scintigraphy using 99mTc-lactosylated human serum albumin (LSA), a newly synthesized radiopharmaceutical with convenient labeling method, in the evaluation. of hepatic functional status, in vivo imaging study with LSA was performed in rats with. acute hepatic injury induced by dimethylnitrosamine (DMN). Results were compared with changes in liver enzyme profiles and histological findings. Methods: DMN (27 mg/kg) was injected i.p. in 20 SD rats to induce acute hepatic injury. Dynamic and static imaging of the chest and abdomen were acquired for 30 minutes after i.v. injection of LSA at the 3rd (DMN-3), 8th (DMN-8), and 21st (DMN-21) days after DMN treatment. Time-activity curves of the heart and the liver were generated from anterior images. Degree of hepatic uptake and blood clearance were evaluated with visual interpretation and semiquantitative analysis using receptor index (LHL3) and index of blood clearance (HH3). Time to maximal binding (Tmax) and slope of the curve (K value) were acquired with maximal likelihood curve fitting method using Prism program. Results: Increases in liver enzymes (AST and ALT) and changes in histological findings (centrilobular necrosis and cellular infiltration) were the most prominent in DMN-3 group, and to a lesser extent after then. Hepatic tracer uptake was lower in DMN-treated rat group. In semiquantitative analysis, LHL3 was significantly lower in DMN-treated rat group than in control group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p99mTc-LSA liver scintigraphy could be used in initial evaluation of acute hepatic injury and follow-up studies for recovery. (authors)

  16. Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury

    Sun-Hee Jang; Sung-woo Cho; Hyun-Min Yoon; Kyung-Jeon Jang; Chun-Ho Song; Cheol-Hong Kim

    2014-01-01

    Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. Methods: Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP a...

  17. Prevention and Therapeutic Effects and Mechanisms of Tanshinone IIA Sodium Sulfonate on Acute Liver Injury Mice Model

    Lunjie Lu

    2016-01-01

    Full Text Available Tanshinone IIA sodium sulfonate (TSS is a water-soluble derivative of tanshinone IIA, which is the main pharmacologically active component of Salvia miltiorrhiza. This study aimed to verify the preventive and therapeutic effects of TSS and its combined therapeutic effects with magnesium isoglycyrrhizinate (MI in D-galactosamine- (D-Gal- induced acute liver injury (ALI in mice. The potential regulatory mechanisms of TSS on ALI were also examined. Our results may provide a basis for the development of novel therapeutics for ALI.

  18. Prevention and Therapeutic Effects and Mechanisms of Tanshinone IIA Sodium Sulfonate on Acute Liver Injury Mice Model

    Lu, Lunjie; Zhou, Jun; Zhang, Jingying; Che, Jun; Jiao, Yang; Zhang, Yusong

    2016-01-01

    Tanshinone IIA sodium sulfonate (TSS) is a water-soluble derivative of tanshinone IIA, which is the main pharmacologically active component of Salvia miltiorrhiza. This study aimed to verify the preventive and therapeutic effects of TSS and its combined therapeutic effects with magnesium isoglycyrrhizinate (MI) in D-galactosamine- (D-Gal-) induced acute liver injury (ALI) in mice. The potential regulatory mechanisms of TSS on ALI were also examined. Our results may provide a basis for the development of novel therapeutics for ALI. PMID:27274751

  19. A Challenge for Diagnosing Acute Liver Injury with Concomitant/Sequential Exposure to Multiple Drugs: Can Causality Assessment Scales Be Utilized to Identify the Offending Drug?

    Roxanne Lim; Hassan Choudry; Kim Conner; Wikrom Karnsakul

    2014-01-01

    Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver ...

  20. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis.

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N; Gonzalez, Frank J; Wang, Guangji; Hao, Haiping

    2016-05-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factorα(TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics-pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL's protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  1. Human bone marrow mesenchymal stem cell-derived hepatocytes improve the mouse liver after acute acetaminophen intoxication by preventing progress of injury.

    Stock, Peggy; Brückner, Sandra; Winkler, Sandra; Dollinger, Matthias M; Christ, Bruno

    2014-01-01

    Mesenchymal stem cells from human bone marrow (hMSC) have the potential to differentiate into hepatocyte-like cells in vitro and continue to maintain important hepatocyte functions in vivo after transplantation into host mouse livers. Here, hMSC were differentiated into hepatocyte-like cells in vitro (hMSC-HC) and transplanted into livers of immunodeficient Pfp/Rag2⁻/⁻ mice treated with a sublethal dose of acetaminophen (APAP) to induce acute liver injury. APAP induced a time- and dose-dependent damage of perivenous areas of the liver lobule. Serum levels of aspartate aminotransferase (AST) increased to similar levels irrespective of hMSC-HC transplantation. Yet, hMSC-HC resided in the damaged perivenous areas of the liver lobules short-term preventing apoptosis and thus progress of organ destruction. Disturbance of metabolic protein expression was lower in the livers receiving hMSC-HC. Seven weeks after APAP treatment, hepatic injury had completely recovered in groups both with and without hMSC-HC. Clusters of transplanted cells appeared predominantly in the periportal portion of the liver lobule and secreted human albumin featuring a prominent quality of differentiated hepatocytes. Thus, hMSC-HC attenuated the inflammatory response and supported liver regeneration after acute injury induced by acetaminophen. They hence may serve as a novel source of hepatocyte-like cells suitable for cell therapy of acute liver diseases. PMID:24758938

  2. Human Bone Marrow Mesenchymal Stem Cell-Derived Hepatocytes Improve the Mouse Liver after Acute Acetaminophen Intoxication by Preventing Progress of Injury

    Peggy Stock

    2014-04-01

    Full Text Available Mesenchymal stem cells from human bone marrow (hMSC have the potential to differentiate into hepatocyte-like cells in vitro and continue to maintain important hepatocyte functions in vivo after transplantation into host mouse livers. Here, hMSC were differentiated into hepatocyte-like cells in vitro (hMSC-HC and transplanted into livers of immunodeficient Pfp/Rag2−/− mice treated with a sublethal dose of acetaminophen (APAP to induce acute liver injury. APAP induced a time- and dose-dependent damage of perivenous areas of the liver lobule. Serum levels of aspartate aminotransferase (AST increased to similar levels irrespective of hMSC-HC transplantation. Yet, hMSC-HC resided in the damaged perivenous areas of the liver lobules short-term preventing apoptosis and thus progress of organ destruction. Disturbance of metabolic protein expression was lower in the livers receiving hMSC-HC. Seven weeks after APAP treatment, hepatic injury had completely recovered in groups both with and without hMSC-HC. Clusters of transplanted cells appeared predominantly in the periportal portion of the liver lobule and secreted human albumin featuring a prominent quality of differentiated hepatocytes. Thus, hMSC-HC attenuated the inflammatory response and supported liver regeneration after acute injury induced by acetaminophen. They hence may serve as a novel source of hepatocyte-like cells suitable for cell therapy of acute liver diseases.

  3. Protective effect of a polysaccharide from Rhizoma Atractylodis Macrocephalae on acute liver injury in mice.

    Han, Bing; Gao, Yang; Wang, Yanli; Wang, Lan; Shang, Zuhui; Wang, Shuang; Pei, Jin

    2016-06-01

    A homogeneous polysaccharide was isolated and purified from Rhizoma Atractylodis Macrocephalae (RAM) and named PRAM2. Its average molecular weight was 19.6×10(3)Da and it was composed of rhamnose, xylose, arabinose, glucose, mannose and galactose in a ratio of 1: 1.3: 1.5: 1.8: 2.1: 3.2. In vitro experiments confirmed that PRAM2 presented an obvious effect to scavenge 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) (DPPH), superoxide anion and hydroxyl radical. In vivo experiments confirmed that PRAM2 could reduce the liver weight, liver index, aspartate transaminase (AST) and alanine aminotransferase (ALT) activities in the serum; meanwhile, PRAM2 could significantly reduce nitric oxide synthase (NOS) activity, and nitric oxide (NO) and malonaldehyde (MDA) contents in the liver tissues, and increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. These results suggest that PRAM2 has a significant in vitro antioxidant activity and a protective effect on CCl4-induced liver injury in mice; the protective effect may be related to its anti-oxidation, its inhibition of NOS activity and NO level and its reduction of the production of free radicals. PMID:26820352

  4. Red Sea Suberea mollis Sponge Extract Protects against CCl4-Induced Acute Liver Injury in Rats via an Antioxidant Mechanism

    Aymn T. Abbas

    2014-01-01

    Full Text Available Recent studies have demonstrated that marine sponges and their active constituents exhibited several potential medical applications. This study aimed to evaluate the possible hepatoprotective role as well as the antioxidant effect of the Red Sea Suberea mollis sponge extract (SMSE on carbon tetrachloride- (CCl4- induced acute liver injury in rats. In vitro antioxidant activity of SMSE was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH assay. Rats were orally administered three different concentrations (100, 200, and 400 mg/kg of SMSE and silymarin (100 mg/kg along with CCl4 (1 mL/kg, i.p., every 72 hr for 14 days. Plasma aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, and total bilirubin were measured. Hepatic malondialdehyde (MDA, reduced glutathione (GSH, nitric oxide (NO, superoxide dismutase (SOD, glutathione peroxidase (GPx, and catalase (CAT were also measured. Liver specimens were histopathologically examined. SMSE showed strong scavenging activity against free radicals in DPPH assay. SMSE significantly reduced liver enzyme activities. Moreover, SMSE significantly reduced hepatic MDA formation. In addition, SMSE restored GSH, NO, SOD, GPx, and CAT. The histopathological results confirmed these findings. The results of this study suggested a potent protective effect of the SMSE against CCl4-induced hepatic injury. This may be due to its antioxidant and radical scavenging activity.

  5. Effect of matrine hydrochloride on liver injury

    CHEN Li-bo; XU Feng; MA Wen-hui

    2008-01-01

    Objective Searching the function that the Injection of the matrine hydrochloride prevents and cures acute chemical liver injury of mice、 immunity liver injury of mice and chronic liver injury of rats. Methods Acute hepatic injury models of mice induced by Chemical poison carbon tetrachloride (CCl4), thioacetamide(TAA), D-galactosamine(D-GalN), immunity hepatic injury model of mice induced by BCG and fat polysaccharide (LPS), chronic liver injury model of rats induced by CCI, were introduced in the experiment. The serum ALT and AST were measured in acute hepatic injury experiments. Serum ALT, AST, AKP, ALB, TP, BiL-T, ereatinine, triglyceride, sialie acid, larninin, hyaluronic acid, type Ⅲ proeollagen and type Ⅳ collagen, hepatic hydroxyproline (HyP) of rats in chronic liver injury animals were determined after Injection of the matrine hydrochloride. Results The Injection of the matrine hydrochloride reduced serum ALT and AST level of acute chemical liver injury of mice induced by CCl4, TAA and D-GaIN. The index of the liver and the spleen of immunity liver injury of mice induced by BCG and LPS were decreased after the injection of matrine hydrochloride treatment. Compared with the model group, the injection may obviously inhibited serum ALT, AST, TP, AKP, TRI, BiL-T, creatinine, triglyceride, sialic acid, laminin , hyaluronic acid , type Ⅲ procollagen and type Ⅳ collagen activity of chronic liver injury of rats induced by CCl4, elevated ALB、A/G, reduced the liver HyP, decreased the index of the liver and the spleen. The liver visual observation, the pathology inspection and the HAI grading result showed the injection may reduce the inflammatory activity in liver tissue, restrain the liver cell damage, reduce the pseudolobuli formation. Conclusions The Injection of matrine hydrochloride had the protective function to acute chemical hepatic injury of mice induced by CCl4、TAA、D-GalN、immunity hepatic injury of mice induced by the BCG and LPS and

  6. The carvacrol ameliorates acute pancreatitis-induced liver injury via antioxidant response.

    Bakır, Murat; Geyikoglu, Fatime; Colak, Suat; Turkez, Hasan; Bakır, Tulay Ozhan; Hosseinigouzdagani, Mirkhalil

    2016-08-01

    Acute pancreatitis (AP) may cause significant persistent multi-organ dysfunction. Carvacrol (CAR) possesses a variety of biological and pharmacological properties. The aim of the present study was to analyze the hepatic protection of CAR on AP induced by cerulein and to explore the underlying mechanism using in vivo studies. The rats were randomized into groups to receive (1) no therapy; (2) 50 µg/kg cerulein at 1-h intervals by four intraperitoneal injection (i.p.); (3) 50, 100 and 200 mg/kg CAR by one i.p.; and (4) cerulein + CAR after 2 h of cerulein injection. 12 h later, serum was provided to assess the blood AST, ALT and LDH values. Also, liver tissues were obtained for histological and biochemical measurements. Liver oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as MDA and changes in tissue antioxidant enzyme levels, SOD, CAT and GSH-Px. Histopathological examination was performed using scoring systems. Oxidative damage to DNA was quantitated in studied tissues of experimental animals by measuring the increase in 8-hydroxydeoxyguanosine (8-OHdG) formations. We found that the increasing doses of CAR decreased pancreatitis-induced MDA and 8-OH-dG levels. Moreover, the liver SOD, CAT and GSH-Px activities in the AP + CAR group were higher than that of the rats in the AP group. In the treatment groups, AST, ALT and LDH were reduced. Besides, necrosis, coagulation and inflammation in the liver were alleviated (p < 0.05). We suggest that CAR could be a safe and potent new drug candidate for treating AP through its antioxidative mechanism of action for the treatment of a wide range of disorders related to hepatic dysfunction. PMID:26350272

  7. Abnormal chloride homeostasis in the substancia nigra pars reticulata contributes to locomotor deficiency in a model of acute liver injury.

    Yan-Ling Yang

    Full Text Available BACKGROUND: Altered chloride homeostasis has been thought to be a risk factor for several brain disorders, while less attention has been paid to its role in liver disease. We aimed to analyze the involvement and possible mechanisms of altered chloride homeostasis of GABAergic neurons within the substantia nigra pars reticulata (SNr in the motor deficit observed in a model of encephalopathy caused by acute liver failure, by using glutamic acid decarboxylase 67 - green fluorescent protein knock-in transgenic mice. METHODS: Alterations in intracellular chloride concentration in GABAergic neurons within the SNr and changes in the expression of two dominant chloride homeostasis-regulating genes, KCC2 and NKCC1, were evaluated in mice with hypolocomotion due to hepatic encephalopathy (HE. The effects of pharmacological blockade and/or activation of KCC2 and NKCC1 functions with their specific inhibitors and/or activators on the motor activity were assessed. RESULTS: In our mouse model of acute liver injury, chloride imaging indicated an increase in local intracellular chloride concentration in SNr GABAergic neurons. In addition, the mRNA and protein levels of KCC2 were reduced, particularly on neuronal cell membranes; in contrast, NKCC1 expression remained unaffected. Furthermore, blockage of KCC2 reduced motor activity in the normal mice and led to a further deteriorated hypolocomotion in HE mice. Blockade of NKCC1 was not able to normalize motor activity in mice with liver failure. CONCLUSION: Our data suggest that altered chloride homeostasis is likely involved in the pathophysiology of hypolocomotion following HE. Drugs aimed at restoring normal chloride homeostasis would be a potential treatment for hepatic failure.

  8. Protective Effect of Procyanidin B2 against CCl4-Induced Acute Liver Injury in Mice

    Bing-Ya Yang

    2015-07-01

    Full Text Available Procyanidin B2 has demonstrated several health benefits and medical properties. However, its protective effects against CCl4-induced hepatotoxicity have not been clarified. The present study aimed to investigate the hepatoprotective effects of procyanidin B2 in CCl4-treated mice. Our data showed that procyanidin B2 significantly decreased the CCl4-induced elevation of serum alanine aminotransferase activities, as well as improved hepatic histopathological abnormalities. Procyanidin B2 also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD, CAT and GSH-Px. Further research demonstrated that procyanidin B2 decreased the expression of TNF-α, IL-1β, cyclooxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS, as well as inhibited the translocation of nuclear factor-kappa B (NF-κB p65 from the cytosol to the nuclear fraction in mouse liver. Moreover, CCl4-induced apoptosis in mouse liver was measured by (terminal-deoxynucleotidyl transferase mediated nick end labeling TUNEL assay and the cleaved caspase-3. Meanwhile, the expression of apoptosis-related proteins Bax and Bcl-xL was analyzed by Western blot. Results showed that procyanidin B2 significantly inhibited CCl4-induced hepatocyte apoptosis, markedly suppressed the upregulation of Bax expression and restored the downregulation of Bcl-xL expression. Overall, the findings indicated that procyanidin B2 exhibited a protective effect on CCl4-induced hepatic injury by elevating the antioxidative defense potential and consequently suppressing the inflammatory response and apoptosis of liver tissues.

  9. Preparation of total flavonoids from loquat flower and its protective effect on acute alcohol-induced liver injury in mice

    Shao-Kang Wu

    2015-03-01

    Full Text Available This study aimed to research the preparation techniques of total flavones from loquat flower (TFLF, its anti-oxidation capacity, and its protective effect on hepatic injury. The best extraction parameters by orthogonal experimentation were water at 100°C, extraction time 2.5 hours, solid/liquid ratio 1:20, and three decoctions. The chromogenic reaction to the flavones showed that loquat flowers mainly contained flavone, flavonol, and flavanone compounds combining ortho-phenolic hydroxyl group structure in the 10–30% ethanol fraction. The anti-oxidant capacity of O2−· was 26.09% and of OH−·was 83.01% by salicylic acid and pyrogallol auto-oxidation. Compared with the model group, TFLF lowered the levels of alanine aminotransferase, aspartate aminotransferase, triglyceride, and malondialdehyde and liver index significantly, and upregulated the expression of adipose triglyceride lipase and Heine oxygenase-1 mRNA. The present findings suggest that TFLF has protective effect on acute alcoholinduced liver injury in mice and may be related to its antioxidant and free-radical scavenging activity.

  10. Fetal liver cells transplantation in the treatment of extremely severe acute radiation injuries induced by large dose irradiation in leukemic patients

    Seven cases of extremely severe acute radiation injuries treated with fetal liver cells transplantation (FLT) are reported. Patients received 6-8 Gy whole body irradiation which was followed by an infusion of fetal liver cell suspension. Hematological reconstitution occurred in all patients and temporary chimera developed in 3 patients after FLT. There were no difference between the hematologic reconstitution in patients with or without chimera

  11. Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury

    de Vries, Heleen A. H.; Ponds, Fraukje A. M.; Nieuwenhuijs, Vincent B.; Morphett, Arthur; Padbury, Robert T. A.; Barritt, Greg J.

    2013-01-01

    Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question. Ma

  12. A Challenge for Diagnosing Acute Liver Injury with Concomitant/Sequential Exposure to Multiple Drugs: Can Causality Assessment Scales Be Utilized to Identify the Offending Drug?

    Roxanne Lim

    2014-01-01

    Full Text Available Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM, Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis.

  13. A challenge for diagnosing acute liver injury with concomitant/sequential exposure to multiple drugs: can causality assessment scales be utilized to identify the offending drug?

    Lim, Roxanne; Choudry, Hassan; Conner, Kim; Karnsakul, Wikrom

    2014-01-01

    Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only) drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM), Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis. PMID:25506455

  14. Mast cell stabilization alleviates acute lung injury after orthotopic autologous liver transplantation in rats by downregulating inflammation.

    Ailan Zhang

    Full Text Available BACKGROUND: Acute lung injury (ALI is one of the most severe complications after orthotopic liver transplantation. Amplified inflammatory response after transplantation contributes to the process of ALI, but the mechanism underlying inflammation activation is not completely understood. We have demonstrated that mast cell stabilization attenuated inflammation and ALI in a rodent intestine ischemia/reperfusion model. We hypothesized that upregulation of inflammation triggered by mast cell activation may be involve in ALI after liver transplantation. METHODS: Adult male Sprague-Dawley rats received orthotopic autologous liver transplantation (OALT and were executed 4, 8, 16, and 24 h after OALT. The rats were pretreated with the mast cell stabilizers cromolyn sodium or ketotifen 15 min before OALT and executed 8 h after OALT. Lung tissues and arterial blood were collected to evaluate lung injury. β-hexosaminidase and mast cell tryptase levels were assessed to determine the activation of mast cells. Tumor necrosis factor α (TNF-α, interleukin (IL-1β and IL-6 in serum and lung tissue were analyzed by enzyme-linked immunosorbent assay. Nuclear factor-kappa B (NF-κB p65 translocation was assessed by Western blot. RESULTS: The rats that underwent OALT exhibited severe pulmonary damage with a high wet-to-dry ratio, low partial pressure of oxygen, and low precursor surfactant protein C levels, which corresponded to the significant elevation of pro-inflammatory cytokines, β-hexosaminidase, and tryptase levels in serum and lung tissues. The severity of ALI progressed and maximized 8 h after OALT. Mast cell stabilization significantly inhibited the activation of mast cells, downregulated pro-inflammatory cytokine levels and translocation of NF-κB, and attenuated OALT-induced ALI. CONCLUSIONS: Mast cell activation amplified inflammation and played an important role in the process of post-OALT related ALI.

  15. Acute liver failure

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  16. Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling

    Lee Hsuan-Shu

    2009-03-01

    Full Text Available Abstract Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI. The present study was undertaken to determine whether D-galactosamine (D-GalN induces ALI via the mitochondrial apoptosis- and proinflammatory cytokine-signaling pathways, and possible mechanism(s by which green tea (GT extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS production from affected hepatocytes, infiltrated leukocytes, and activated Kupffer cells. D-GalN evoked cytosolic Bax and mitochondrial cytochrome C translocation and activated proinflammatory nuclear factor-kappa B (NF-κB and activator protein-1 (AP-1 translocation, contributing to the increase of intercellular adhesion molecule-1 expression, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL-positive hepatocytes, multiple plasma cytokines and chemokines release, and alanine aminotransferase (ALT activity. An altered biliary secretion profile of several acute phase proteins directly indicates oxidative stress affecting intracellular trafficking in the hepatocyte. GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms. In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver. GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.

  17. Human Bone Marrow Mesenchymal Stem Cell-Derived Hepatocytes Improve the Mouse Liver after Acute Acetaminophen Intoxication by Preventing Progress of Injury

    Peggy Stock; Sandra Brückner; Sandra Winkler; Dollinger, Matthias M.; Bruno Christ

    2014-01-01

    Mesenchymal stem cells from human bone marrow (hMSC) have the potential to differentiate into hepatocyte-like cells in vitro and continue to maintain important hepatocyte functions in vivo after transplantation into host mouse livers. Here, hMSC were differentiated into hepatocyte-like cells in vitro (hMSC-HC) and transplanted into livers of immunodeficient Pfp/Rag2−/− mice treated with a sublethal dose of acetaminophen (APAP) to induce acute liver injury. APAP induced a time- and dose-depen...

  18. Response of two protective agents to acute injury induced by 12C6+ ions in mouse liver

    The present study was to evaluate the effect and mechanism of N-acetylcysteine (NAC) and Acetyl-L-Carnitine hydrochloride (ALCAR) against 12C6+ ion beams on acute injury in the mouse liver. Pretreated with NAC (100 mg/kg) and ALCAR (100 mg/kg), Kun-Ming mice were exposed to whole-body irradiation with the dose of 4 Gy. Mice were killed 2 h after irradiation, and then the liver tissues were quickly removed. TAC was measured by using chemical reagent kids, and DNA-single strand breaks were determined by single cell gel electrophoresis, and the percentage of cell apoptosis were assayed by flow cytometry method. The results showed that NAC and ALCAR pretreatment significantly enhanced TAC (P12C6+ ions is stronger than that of NAC (P12C6+ ions in mice. In this study, NAC and ALCAR exert their radioprotective effect by virtue of resisting oxidative stress, enhancing TAC, alleviating DNA-single strand breaks as well as cell apoptosis. Furthermore, the data imply that NAC and ALCAR may be suitable and promising as radioprotective drug against carbon heavy ions. (authors)

  19. Expression of VEGF protein of lung and liver in GM-CSF gene transferred mice after neutron acute injury

    Objective: To study lung and liver vascular endothelial growth factor (VEGF) protein expression changes in granulocyte-macrophage colony-stimulating factor(GM-CSF) transgene mice after neutron exposure. Methods: Male BALB/C mice were irradiated with neutron, in dose of 0.6Gy, the mice were divided into the non-transfer group and the gene transfer group. In the gene transfer group, hGM-CSF gene was transfered by electroporation in vivo 24 h prior to exposure. Animals in the two groups were sacrificed at the 1st, 14th, 28th day, using pathologic test, immunohistochemica test and Western blot to study VEGF protein expression in lung and liver. Results: From 14 d to 28 d after exposure, the levels of VEGF protein expression in the mice in the genetransfer group was significantly higher than that in the non-transfer group. Conclusion: GM-CSF in vivo gene transfer in mice significantly promote angiogenesis and restoration in the climax and recovery phase acute injury caused by neutron. (authors)

  20. Autophagy and Liver Ischemia-Reperfusion Injury

    Raffaele Cursio

    2015-01-01

    Full Text Available Liver ischemia-reperfusion (I-R injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS, leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

  1. Management of carbon tetrachloride-induced acute liver injury in rats by syngeneic hepatocyte transplantation in spleen and peritoneal cavity

    Charalampos Pilichos; Despina Perrea; Maria Demonakou; Athena Preza; Ismini Donta

    2004-01-01

    AIM: Acute hepatitis may seldom have a fulminant course.In the treatment of this medical emergency, potential liver support measure must provide immediate and sufficient assistance to the hepatic function. The goal of our study was to study the adequacy of hepatocyte transplantation (HCTx) in two different anatomical sites, splenic parenchyma and peritoneal cavity, in a rat model of reversible acute hepatitis induced by carbon tetrachloride (CCl4).METHODS: After CCl4 intoxication, 84 male Wistar rats used as recipients were divided in to four experimental groups accordingly to their treatment: Group A (n=24): intrasplenic transplantation of 10x106 isolated hepatocytes, Group B (n=24):intraperitoneal transplantation of 20xL06 isolated hepatocytes attached on plastic microcarriers, Group C (n= 18): i ntrasplenic injection of 1 mL normal saline (sham-operated controls),Group D (n=18): intraperitoneal injection of 2.5 mL normal saline (sham-operated controls). Survival, liver function tests (LFT) and histology were studied in all four groups, on d 2,5 and 10 post-HCTx.RESULTS: The ten-day survival (and mean survival) in the 4 groups was 72.2% (8.1±3.1), 33.3% (5.4±3.4), 0%(3.1±1.3) and 33.3% (5.4±3.6) in groups A, B, C, D,respectively (PAB<0.05, PAC<0.05, PBD=NS). In the final survivors, LFT (except alkaline phosphatase) and hepatic histology returned to normal, independently of their previous therapy. Viable hepatocytes were identified within splenic parenchyma (in group A on d 2) and both in the native liver and the fatty tissue of abdominal wall (in group B on d 5).CONCLUSION: A significantly better survival of the intrasplenically transplanted animals has been demonstrated.Intraperitoneal hepatocytes failed to promptly engraft. A different timing between liver injury and intraperitoneal HCTx may give better results and merits further investigation.

  2. Lethal acute liver failure in a patient treated with sunitinib.

    Guillen, S S; Meijer, M; de Jongh, F E

    2016-01-01

    Sunitinib is a tyrosine kinase inhibitor that is used as an anticancer drug in renal cell carcinoma (RCC), pancreatic neuroendocrine tumours (PNETs) and gastrointestinal stromal tumour. Elevated liver enzymes are frequently observed during treatment but acute liver failure is uncommon. We describe a case of fulminant acute liver failure and acute kidney injury during treatment with sunitinib for metastatic RCC. PMID:26933184

  3. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  4. Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

    Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsuneyama, Koichi [Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Sugitani, Toyama 930‐0194 (Japan); Endo, Shinya [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsukui, Tohru [Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka 350‐1241 (Japan); Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@p.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan)

    2012-10-01

    Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

  5. The Effect of Citrus Peel Extracts on Cytokines Levels and T Regulatory Cells in Acute Liver Injury

    Ia Pantsulaia

    2014-01-01

    Full Text Available Background. T cell-mediated immune responses contribute to the hepatocellular injury during autoimmune hepatitis, viral infection, and hepatotoxins. Pharmacological compounds regulating immune responses are suitable candidates for prevention/treatment of this pathology. Therefore, the main aim of this study was to define the effects of antioxidant, anti-inflammatory mixture of citrus peel extract (CPE on the immune-mediated liver injury. Methods. The influence of CPE on liver injury was determined by the activity of transaminases in plasma and the histological changes. Anti-inflammatory and antioxidant effects were studied by measuring frequency of T regulatory cells (Tregs, cytokines (TNF-α, IL-10, and IFN-γ, and nitric oxide levels. Results. The CPE application notably prevents development of liver injury through decreasing levels of both cytokines (TNF-alpha, INF and regulatory T cells and increasing levels of IL-10. CPE injection also diminished the serum NO, which in turn resulted in evident reduction of the liver damage. Conclusion. Our findings represent the primary preclinical data indicating that the CPE in vivo could ameliorate Con A induced hepatitis. The low dose of CPE most likely can be used for the treatment of the T cell-mediated liver injury as in autoimmune hepatitis, alcoholic hepatitis, and chronic viral hepatitis.

  6. Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

    Li-Mei Zhang; Dian-Wu Liu; Jian-Bo Liu; Xiao-Lin Zhang; Xiao-Bo Wang; Long-Mei Tang; Li-Qin Wang

    2005-01-01

    AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the

  7. Acute kidney injury.

    Lang, Joanna; Zuber, Kim; Davis, Jane

    2016-04-01

    Acute kidney injury (AKI) complicates up to 20% of all hospital admissions. Responding to the increase in admissions, complications, mortality, morbidity, and cost of AKI, Kidney Disease: Improving Global Outcomes convened an expert panel to study the issue, review the literature, and publish guidelines to evaluate and treat patients with AKI in the acute setting. This article reviews those guidelines. PMID:27023656

  8. Acute liver failure

    Bernal, William; Lee, William M; Wendon, Julia;

    2015-01-01

    Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver...... transplantation (ELT) is an established treatment option. These improvements in care are such that the majority of patients may now be expected to survive (Fig. 1). Key features of the condition have changed dramatically over time, with a remarkable fall in the incidence of cerebral edema and intracranial...

  9. Structural characterization, molecular modification and hepatoprotective effect of melanin from Lachnum YM226 on acute alcohol-induced liver injury in mice.

    Song, Sheng; Li, Shenglan; Su, Nana; Li, Jinglei; Shi, Fang; Ye, Ming

    2016-08-10

    In this paper, the possible structural formula of the intracellular homogeneous melanin of Lachnum YM226 (LM) was concluded based on an elemental assay, ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), mass spectrometry (MS) and equivalent series resistance (ESR). Meanwhile, a d-glucosamine melanin derivative (GLM) was also prepared and its cytotoxicity was evaluated using the MTT assay. The hepatoprotective effect of LM and GLM was evaluated in an acute alcohol-induced liver injury model. The results showed that pretreatments with LM and GLM markedly decreased subsequent alcohol elicited acute hepatic oxidative and inflammatory stress via improving the activity of antioxidant enzymes (glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), and total superoxide dismutase (SOD)), reducing hepatic levels of nuclear transcription factor (NF-κB), cytokines related to its activation (interleukin (IL)-6, tumor necrosis factor (TNF)-α and macrophage chemoattractant protein (MCP)-1) and hepatic activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. The protection properties of alcoholic liver injury of GLM were more obvious than that of LM at the same dose. The present findings recommend that LM and GLM may be used as a prototype for the prevention of alcoholic liver injury. PMID:27485489

  10. the Pathogenesis of acute on Chronic Hepatitis B liver Failure

    Zhao-chun Chi; Quan-jiang Dong; Chang-xin Geng

    2014-01-01

    Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would beneift for the prognosis and raise the survival rate of patients.

  11. Secretory phospholipase A2 mediates progression of acute liver injury in the absence of sufficient cyclooxygenase-2

    Previous studies have shown that injury initiated by toxicants progresses even after most of the toxicant is eliminated from the body. One mechanism of progression of injury is the extracellular appearance of hydrolytic enzymes following leakage or upon cell lyses. Under normal conditions, after exposure to low to moderate doses of toxicants, secretory phospholipase A2 (sPLA2) and other hydrolytic enzymes are known to appear in the extracellular spaces in order to cleanup the post-necrotic debris in tissues. We tested the hypothesis that sPLA2 contributes to progression of toxicant-initiated liver injury because of hydrolysis of membrane phospholipids of hepatocytes in the perinecrotic areas in the absence of sufficient cyclooxygenase-2 (COX-2). Male Sprague-Dawley rats were administered either a moderately hepatotoxic dose (MD, 2 ml CCl4/kg, ip) or a highly hepatotoxic dose (HD, 3 ml CCl4/kg, ip) of CCl4. After MD, liver sPLA2 and COX-2 were co-localized in the necrotic and perinecrotic areas and their activities in plasma and liver increased before decreasing in tandem with liver injury (ALT and histopathology) leading to 100% survival. In contrast, after the HD, high extracellular and hepatic sPLA2 activities were accompanied by minimal COX-2 activity and localization in the liver throughout the time course. This led to progression of liver injury and 70% mortality. These data suggested a destructive role of sPLA2 in the absence of sufficient COX-2. Time- and dose-dependent destruction of hepatocytes by sPLA2 in isolated hepatocyte incubations confirmed the destructive ability of sPLA2 when present extracellularly, suggesting its ability to spread injury in vivo. These findings suggest that sPLA2, secreted for cleanup of necrotic debris upon initiation of hepatic necrosis, requires the co-presence of sufficiently induced COX-2 activity to prevent the run-away destructive action of sPLA2 in the absence of the tissue protective mechanisms afforded by COX-2

  12. Rapid Diagnosis of acute kidney injury (AKI associated with cardiac surgery, using the liver type fatty acid binding protein (L-FABP biomarker

    Mirbagheri L

    2012-01-01

    Full Text Available Background and objectives: cardiac surgery is often associated with acutekidney injury (AKI. Nowadays, AKI is typically diagnosed by an increase inserum creatinine, which is a delayed and unreliable biomarker. Recent studiesrecommended using the liver type fatty acid binding protein (L-FABP as anearly biomarker.Material and Methods: The urine samples of 18 adult patients undergoingcardiac surgery were collected in different times before (2, 4,8,24 hour andafter cardiac surgery for detection of L-FABP by Elisa.Results: The results from ELISA test show that the increasing amount of LFABPin urine samples of 4 patients is a diagnostic indicator for AKI. Themean concentration of L-FABP has increased up to 17 times at 8 hours aftercardiac surgery compared to before surgery.Conclusion: according to our findings, we speculated that the urinary L-FABPcan be a reliable and rapid biomarker for diagnosis of acute kidney injury.Key words: Acute Kidney Injury, Liver type Fatty Acid Binding Protein,Cardiac surgery

  13. Acute Ethanol Pretreatment Increases FAS-Mediated Liver Injury in Mice: Role of Oxidative Stress and CYP2E1-Dependent and Independent Pathways

    Wang, Xiaodong; Cederbaum, Arthur I.

    2006-01-01

    This study evaluated whether acute ethanol pretreatment potentiates Fas-mediated liver injury and if oxidative stress and CYP2E1 play a role in any enhanced hepatotoxicity. There were 3-fold increases of transaminases and more extensive apoptotic necrosis of hepatocytes, and focal hemorrhages of the hepatic lobule in mice treated with Jo2 plus ethanol compared to saline control or to mice treated with Jo2 or ethanol alone. CYP2E1 catalytic activity and protein were increased 2-fold by the acu...

  14. Naproxen-induced liver injury

    Sharif Ali; Jason D Pimentel; Chan Ma

    2011-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractablepruritusthatdevelopedshortlyaftertakingnaproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS:  Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

  15. Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

    Andres F. Carrion

    2010-01-01

    Full Text Available Propylthiouracil- (PTU- induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.

  16. 盐酸丙帕他莫致急性肝损伤%Acute liver injury due to propacetamol hydrochloride

    杨思芸; 潘昭平; 胡玉兰; 柳华; 王龙飞; 胡晓燕

    2015-01-01

    1例45岁男性患者行左侧颌面部和颈部肿物切除术,术前丙氨酸转氨酶( ALT)19 U/L,天冬氨酸转氨酶(AST)32 U/L,γ-谷氨酰转移酶(GGT)146 U/L。术后给予盐酸丙帕他莫2.0 g入0.9%氯化钠注射液100 ml静脉滴注,1次/12 h。术后第8天复查肝功能示ALT 642 U/L,AST 692 U/L, GGT 368 U/L。患者无恶心、呕吐、腹胀、纳差等不适症状,皮肤、巩膜无黄染,肝区无压痛。考虑为盐酸丙帕他莫所致急性肝损伤。当日停用盐酸丙帕他莫,给予多烯磷脂酰胆碱、还原型谷胱甘肽、N-乙酰半胱氨酸等保肝治疗。停用盐酸丙帕他莫第8天,ALT 87 U/L,AST 341 U/L,GGT 354 U/L;第18天,ALT 84 U/L,AST 36 U/L,GGT 276 U/L;第32天,ALT 24 U/L,AST 17 U/L,GGT 36 U/L。%A 45-year-old male received a lump resection on left maxillofacial and cervical region. Before treatment,the laboratory test results were as follows:alanine aminotransferase( ALT)19 U/L, aspartate aminotransferase( AST)32 U/L,gamma glutamyltransferase( GGT)146 U/L. He was given an intravenous infusion of propacetamol hydrochloride 2. 0 g in 0. 9% sodium chloride 100 ml twice daily. The laboratory tests were as follows:alanine aminotransferase 642 U/L,aspartate aminotransferase 692 U/L, gamma glutamyltransferase 368 U/L on day 8 after operation. The patient had no symptoms of nausea, vomiting,abdominal distention,and poor appetite. There was no tenderness in his hepatic zones. He was considered as acute liver injury due to propacetamol hydrochloride. Propacetamol hydrochloride was discontinued immediately and liver-protective drugs such as polyene phosphatidylcholine, reduced glutathione,and N-acetyl cysteine were given. On day 8 of drug withdrawal,the results of laboratory tests were as follows:ALT 87 U/L,AST 341 U/L,GGT 354 U/L. On day 32 of drug withdrawal,the laboratory tests results were as follows:ALT 24 U/L,AST 17 U/L,GGT 36 U/L.

  17. Perillyl alcohol protects against ethanol induced acute liver injury in Wistar rats by inhibiting oxidative stress, NFκ-B activation and proinflammatory cytokine production

    Oxidative stress and inflammation are two major etiological factors that are suggested to play key roles in the development of ethanol induced liver injury. Release of proinflammatory cytokine like tumor necrosis factor alpha (TNF-α) and activation of nuclear factor kappa-B (NFκ-B) may strongly intensify inflammation and cell damage. Additionally, reactive oxygen species (ROS) also exerts significant effect in this whole cell signaling machinery. The present study was designed to investigate the protective effects of perillyl alcohol (POH) on ethanol-induced acute liver injury in Wistar rats and its probable mechanism. We have successfully demonstrated that pre-treatment with POH, besides exerting antioxidant activity might be able to modulate TNF-α release and NFκ-B activation. Rats were divided into five groups and treated with ethanol or POH via an intragastric tube for one week. Control group was treated with vehicle, and ethanol treated group was given ethanol (5 g/kg body wt). Animal of treatment groups were pretreated with POH (50 and 100 mg/kg body wt) and have been given ethanol. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase and hepatic malondialdehyde were increased significantly by ethanol treatment. Ethanol administration decreased hepatic reduced glutathione content and various antioxidant enzymes activity. TNF-α production and NFκ-B activation was also found to be increased after ethanol administration. POH pre-treatment significantly ameliorates ethanol induced acute liver injury possibly by inhibition of lipid peroxidation, replenishment of endogenous enzymatic and non-enzymatic defense system, downregulation of TNF-α as well as NFκ-B.

  18. Protective effect of naringenin against acetaminophen-induced acute liver injury in metallothionein (MT)-null mice.

    Lv, Yingjian; Zhang, Baoxu; Xing, Guozhen; Wang, Fuqiang; Hu, Zhewen

    2013-02-01

    Naringenin is a natural flavonoid aglycone of naringin that has been reported to have a wide range of pharmacological properties, such as antioxidant activity and free radical scavenging capacity. This study was designed to examine the hepatoprotective effect of naringenin against acetaminophen (250 mg kg(-1), sc) in metallothionein (MT)-null mice. 42 SPF MT-knockout mice were used. Naringenin (200, 400, and 800 mg kg(-1), ig) was administered for 4 days before exposure to acetaminophen (250 mg kg(-1), sc). Liver injury was measured by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as liver malondialdehyde (MDA). The glutathione-to-oxidized glutathione ratio (GSH/GSSG) was also assessed. The evidence of liver injury induced by acetaminophen included not only a significant increase in the levels of serum ALT, AST, LDH and liver MDA, and also a significant decrease in GSH/GSSG. Pretreatment of mice with naringenin at 400 and 800 mg kg(-1) reversed the altered parameters. Such reversal effects were dose-dependent: ALT decreased 78.62% and 98.03%, AST decreased 88.35% and 92.64%, LDH decreased 76.54% and 81.63%, MDA decreased 48.59% and 66.27% at a dose of 400 and 800 mg kg(-1) respectively; GSH/GSSG increased 22.57% and 16.93% at a dose of 400 and 800 mg kg(-1) respectively. Histopathological observation findings were also consistent with these effects. Together, this study suggests that naringenin can potentially reverse the hepatotoxic damage of acetaminophen intoxication in MT-null mice. PMID:23142768

  19. Therapeutic hypothermia for acute liver failure

    Stravitz, R.T.; Larsen, Finn Stolze

    2009-01-01

    transplantation or spontaneous liver regeneration follows in short order. To buy time, the induction of therapeutic hypothermia (core temperature 32 degrees C-35 degrees C) has been shown to effectively bridge patients to transplant. Similar to the experience in patients with cerebral edema after other neurologic...... of liver injury. Hypothermia has not been adequately studied for its safety and theoretically may increase the risk of infection, cardiac dysrhythmias, and bleeding, all complications independently associated with acute liver failure. Therefore, although an ample body of experimental and human data...

  20. Lung Injury in Acute Pancreatitis

    Raffaele Pezzilli; Lara Bellacosa; Cristina Felicani

    2009-01-01

    Most knowledge has been accumulated on the mechanisms involved in the development of distant organ injuries during the course of severe acute pancreatitis. Among the various distant organ dysfunctions, both the development of acute lung injury and acute respiratory distress syndrome represent serious complications. In the following paragraphs the pathophysiological mechanisms capable of determining lung injury during the course of acute pancreatitis will be reviewed. Pancreatic Enzymes and...

  1. An Update on Drug-induced Liver Injury

    Devarbhavi, Harshad

    2012-01-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver ...

  2. Acute kidney injury following isotretinoin treatment

    Armaly, Zaher; Haj, Shehadeh; Bowirrat, Abdalla; Alhaj, Mohammed; Jabbour, Adel; Fahoum, Yumna; Abassi, Zaid

    2013-01-01

    Patient: Female, 17 Final Diagnosis: Acute kidney injury Symptoms: Flank pain • nausea • vomiting Medication: Isotretinoin Clinical Procedure: Acne treatment Specialty: Nephrology Objective: Unknown etiology Background: Isotretinoin is widely used for the treatment of acne that is unresponsive to topical therapy. Despite its efficacy, isotretinoin has various adverse effects, including cheilitis, increased risk of cutaneous Staphylococcus aureus infections, and liver function abnormalities. C...

  3. The microbiota regulates susceptibility to Fas-mediated acute hepatic injury

    Celaj, Stela; Gleeson, Michael W; Jie DENG; O'Toole, George A.; Hampton, Thomas H.; Toft, Martin F.; Morrison, Hilary G; Sogin, Mitchell L.; Putra, Juan; Suriawinata, Arief A.; Gorham, James D.

    2014-01-01

    Whereas a significant role for intestinal microbiota in affecting the pathogenesis and progression of chronic hepatic diseases is well documented, the contribution of the intestinal flora to acute liver injury has not been extensively addressed. Elucidating the influence of the intestinal microbiota on acute liver inflammation would be important for better understanding the transition from acute injury to chronic liver disease. Using the Concanavalin A (ConA)-induced liver injury model in lab...

  4. The risk of acute liver injury among users of antibiotic medications in the protect project: The results of a nested case-control study using european outpatient healthcare data

    Brauer, Ruth; Douglas, Ian; Rodriguez, Luis Alberto Garcia; Bate, Andrew; Smeeth, Liam; Reynolds, Robert; Klungel, Olaf; Ruigomez, Ana

    2014-01-01

    Background: The estimated incidence of antibiotic induced acute liver injury (ALI) varies widely, depending on the case definition and source population used. Objectives: We aimed to compare the risk of ALI associated with exposure to any type of antibiotic in a Spanish and United Kingdom (UK) datab

  5. Clinical usefulness of urinary liver-type fatty-acid-binding protein as a perioperative marker of acute kidney injury in patients undergoing endovascular or open-abdominal aortic aneurysm repair

    Obata, Yumi; Kamijo-Ikemori, Atsuko; Ichikawa, Daisuke; Sugaya, Takeshi; Kimura, Kenjiro; Shibagaki, Yugo; Tateda, Takeshi

    2015-01-01

    Purpose Acute kidney injury (AKI) is common after cardiovascular surgery and is usually diagnosed on the basis of the serum creatinine (SCr) level and urinary output. However, SCr is of low sensitivity in patients with poor renal function. Because urinary liver-type fatty-acid-binding protein (L-FABP) reflects renal tubular injury, we evaluated whether perioperative changes in urinary L-FABP predict AKI in the context of abdominal aortic repair. Methods Study participants were 95 patients who...

  6. Plasma osteopontin in acute liver failure

    Srungaram, Praveen; Rule, Jody A; Yuan, He Jun;

    2015-01-01

    BACKGROUND: Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function in the...... setting of massive hepatocyte injury. METHODS: OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1...... and 3 days after undergoing spine fusion (SF) surgery as a model for acute inflammation. RESULTS: Median plasma OPN levels across all etiologies of ALF patients were elevated 10- to 30-fold: overall median 1055ng/mL; range: 33-19,127), when compared to healthy controls (median in pre-SF patients: 41ng...

  7. Acute liver failure associated with Garcinia cambogia use.

    Corey, Rebecca; Werner, K Tuesday; Singer, Andrew; Moss, Adyr; Smith, Maxwell; Noelting, Jessica; Rakela, Jorge

    2016-01-01

    Millions of Americans regularly use herbal supplements, but many are unaware of the potential hidden dangers. Numerous supplements have been associated with hepatotoxicity and, indeed dietary/herbal supplements represent an increasingly common source of acute liver injury. We report a case of acute liver failure requiring liver transplantation associated with the use of Garcinia cambogia, a supplement widely promoted for weight loss. When patients present with acute hepatitis or liver failure from an unknown etiology, a careful history of supplement use should be performed. PMID:26626648

  8. Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells in acute liver injured mice

    Peng, Yuan; Chen, Qian; Yang, Tao; Tao, Yanyan; Lu, Xiong; Liu, Chenghai

    2014-01-01

    Cultured mycelium Cordyceps sinensis (CMCS) was widely used for a variety of diseases including liver injury, the current study aims to investigate the protective effects of CMCS on liver sinusoidal endothelial cells (LSECs) in acute injury liver and related action mechanisms. The mice were injected intraperitoneally with lipopolysaccharide (LPS) and d-galactosamine (D-GalN). 39 male BABL/c mice were randomly divided into four groups: normal control, model control, CMCS treatment and 1,10-phe...

  9. Acute liver failure and liver transplantation.

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2013-08-01

    Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted. PMID:25343108

  10. [Acute kidney injury in children].

    Amira-Peco-Antić; Paripović, Dusan

    2014-01-01

    Acute kidney injury (AKI) is a clinical condition considered to be the consequence of a sudden decrease (> 25%) or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN) are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary) diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis) jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP). Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients. PMID:25033598

  11. Acute kidney injury in children

    Peco-Antić Amira

    2014-01-01

    Full Text Available Acute kidney injury (AKI is a clinical condition considered to be the consequence of a sudden decrease (>25% or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL, cystatin C, kidney injury molecule-1 (KIM-1, interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP. Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients.

  12. Perioperative acute kidney injury

    Calvert Stacey

    2012-07-01

    Full Text Available Abstract Acute kidney injury (AKI is a serious complication in the perioperative period, and is consistently associated with increased rates of mortality and morbidity. Two major consensus definitions have been developed in the last decade that allow for easier comparison of trial evidence. Risk factors have been identified in both cardiac and general surgery and there is an evolving role for novel biomarkers. Despite this, there has been no real change in outcomes and the mainstay of treatment remains preventive with no clear evidence supporting any therapeutic intervention as yet. This review focuses on definition, risk factors, the emerging role of biomarkers and subsequent management of AKI in the perioperative period, taking into account new and emerging strategies.

  13. Review of liver injury associated with dietary supplements.

    Stickel, Felix; Kessebohm, Kerstin; Weimann, Rosemarie; Seitz, Helmut K

    2011-05-01

    Dietary supplements (DS) are easily available and increasingly used, and adverse hepatic reactions have been reported following their intake. To critically review the literature on liver injury because of DSs, delineating patterns and mechanisms of injury and to increase the awareness towards this cause of acute and chronic liver damage. Studies and case reports on liver injury specifically because of DSs published between 1990 and 2010 were searched in the PubMed and EMBASE data bases using the terms 'dietary/nutritional supplements', 'adverse hepatic reactions', 'liver injury'; 'hepatitis', 'liver failure', 'vitamin A' and 'retinoids', and reviewed for yet unidentified publications. Significant liver injury was reported after intake of Herbalife and Hydroxycut products, tea extracts from Camellia sinensis, products containing usnic acid and high contents of vitamin A, anabolic steroids and others. No uniform pattern of hepatotoxicity has been identified and severity may range from asymptomatic elevations of serum liver enzymes to hepatic failure and death. Exact estimates on how frequent adverse hepatic reactions occur as a result of DSs cannot be provided. Liver injury from DSs mimicking other liver diseases is increasingly recognized. Measures to reduce risk include tighter regulation of their production and distribution and increased awareness of users and professionals of the potential risks. PMID:21457433

  14. Diagnosis of Acute Groin Injuries

    Serner, Andreas; Tol, Johannes L; Jomaah, Nabil;

    2015-01-01

    BACKGROUND: Acute groin injuries are common in high-intensity sports, but there are insufficient data on injury characteristics such as injury mechanisms and clinical and radiological findings. PURPOSE: To describe these characteristics in a cohort of athletes. STUDY DESIGN: Cross-sectional study......; Level of evidence, 3. METHODS: A total of 110 male athletes (mean age, 25.6 ± 4.7 years) with sports-related acute groin pain were prospectively included within 7 days of injury from August 2012 to April 2014. Standardized history taking, a clinical examination, magnetic resonance imaging (MRI), and....../or ultrasound (US) were performed. RESULTS: The most frequent injury mechanism in soccer was kicking (40%), and change of direction was most frequent in other sports (31%). Clinically, adductor injuries accounted for 66% of all injuries and primarily involved the adductor longus on imaging (91% US, 93% MRI...

  15. Fenofibrate-induced liver injury

    Kazufumi Dohmen; Hiromi Tshibashi; Chun Yang Wen; Shinya Nagaoka; Koji Yano; Seigo Abiru; Toshihito Ueki; Atsumasa Komori; Manabu Daikoku; Hiroshi Yatsuhashi

    2005-01-01

    @@ TO THE EDITOR Fenofibrate is a member of such fibrate class agents as bezafibrate and it work as a ligand of PPARα, and also shows a potent triglyceride-lowering effect. The elevation of aminotransferase levels has been frequently observed after the administration of fenofibrate and this phenomenon is considered to be non-pathological because fenofibrate activates the gene expression of the aminotransferases. Recently, fenofibrate has been used not only for hypercholesterolemia but also for primary biliary cirrhosis (PBC)[1,2]. However, the occurrence of liver injury induced by fenofibrate has not yet been reported written in the English literature. We herein report a rare case of liver injury due to the oral use of this drug.

  16. [Ascites and acute kidney injury].

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo

    2016-07-01

    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years. PMID:27571467

  17. Acute kidney injury in children.

    Merouani, A; Flechelles, O; Jouvet, P

    2012-04-01

    Acute kidney injury (AKI) affects 5% of critically ill hospitalized children and is a risk factor for increased morbidity and mortality. The current review focuses on new definitions of acute kidney injury, standardized to reflect the entire spectrum of the disease, as well as on ongoing research to identify early biomarkers of kidney injury. Its also provides an overview of current practice and available therapies, with emphasis on new strategies for the prevention and pharmacological treatment of diarrhea-associated hemolytic uremic syndrome. Furthermore, a decision-making algorithm is presented for the use of renal replacement therapies in critically ill children with AKI. PMID:22495187

  18. Therapeutic modulation of liver ischaemia reperfusion injury

    Sheth, H.

    2011-01-01

    Liver Ischaemia Reperfusion Injury (IRI) leads to production of reactive oxygen species and cytokines, which affects hepatocellular function following liver resection and transplantation. This thesis examines 2 hypotheses: 1) The role of intravenous glycine in amelioration of liver IRI in a in vivo animal model of partial lobar liver IRI. 2) Does prophylactically administered N-acetylcysteine prevent liver IRI in patients undergoing elective liver resection. Materials ...

  19. Role of IRAK-M in alcohol induced liver injury.

    Yipeng Wang

    Full Text Available Increasing evidence suggests that innate immunity plays an important role in alcohol-induced liver injury and most studies have focused on positive regulation of innate immunity. The main objective of this study was to investigate the negative regulator of innate immunity, IL-1/Toll-like receptor (TLR signaling pathways and interleukin receptor-associated kinase-M (IRAK-M in alcoholic liver injury. We established an alcohol-induced liver injury model using wild type and IRAK-M deficient B6 mice and investigated the possible mechanisms. We found that in the absence of IRAK-M, liver damage by alcohol was worse with higher alanine transaminase (ALT, more immune cell infiltration and increased numbers of IFNγ producing cells. We also found enhanced phagocytic activity in CD68(+ cells. Moreover, our results revealed altered gut bacteria after alcohol consumption and this was more striking in the absence of IRAK-M. Our study provides evidence that IRAK-M plays an important role in alcohol-induced liver injury and IRAK-M negatively regulates the innate and possibly the adaptive immune response in the liver reacting to acute insult by alcohol. In the absence of IRAK-M, the hosts developed worse liver injury, enhanced gut permeability and altered gut microbiota.

  20. Role of Dehydroepiandrosterone on Oxidative Stress Bio markers in CCl4 Induced Acute Liver Injury in Rats

    Liver disease has become one of the serious health problems which threaten human as it is exposed to many kinds of xenobiotics and therapeutic agents. Moreover, the rapid growing morbidity and mortality from liver disease are attributed to the increasing number of chemical compounds and environmental pollution. Unfortunately, in the modern era of medicine, there is no specific treatment to counter the menacing impact of these dreaded diseases. Dehydroepiandrosterone (DHEA) is a widely studied steroid hormone with multi-functional properties. Reports suggested that some of the many activities of DHEA are due to its protective effect against lipid peroxidation. Nevertheless, the antioxidant properties of DHEA are still the subject of debate. In the current study, a significant decrease was occurred in liver glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) as a result of carbon tetrachloride (CCl4) administration. On the other hand, significant elevations in hepatic enzymes (ALT and AST), total lipids, cholesterol, MDA, tumor necrosis factor-γ, total oxidant capacity and poly (ADP-ribose) polymerase were recorded. These disturbances in all the studied parameters were ameliorated after the toxicated rats were treated with 100/ mg/100 g/day DEHA which depend on the time of treatment (1 and 2 weeks). These findings are consistent with the concept that DHEA is an antioxidant agent

  1. Preliminary studies on antihepatotoxic effect of Physalis peruviana Linn. (Solanaceae) against carbon tetrachloride induced acute liver injury in rats.

    Arun, M; Asha, V V

    2007-04-20

    Physalis peruviana is a medicinal herb used by Muthuvan tribes and Tamilian native who reside in the shola forest regions of Kerala, India against jaundice. It was evaluated for its antihepatotoxic, phytochemical analysis and the acute toxicity of the most promising extract in rats. Water, ethanol and hexane extracts of Physalis peruviana (500mg/kg body weight) showed antihepatotoxic activities against CCl(4) induced hepatotoxicity. The ethanol and hexane extracts showed moderate activity compared to water extract, which showed activity at a low dose of 125mg/kg. The results were judged from the serum marker enzymes. Histopathological changes induced by CCl(4) were also significantly reduced by the extract. Further, the extract administration to rats resulted in an increase in hepatic GSH and decrease in MDA. Preliminary phytochemical analysis revealed the presence of various components in the crude aqueous extract. The extract was found to be devoid of any conspicuous acute toxicity in rats. PMID:17161567

  2. Renal Liver-Type Fatty Acid Binding Protein (L-FABP) Attenuates Acute Kidney Injury in Aristolochic Acid Nephrotoxicity

    Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro

    2011-01-01

    Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up t...

  3. Biomarkers in Acute Lung Injury

    Bhargava, Maneesh; Wendt, Chris

    2012-01-01

    Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) result in high permeability pulmonary edema causing hypoxic respiratory failure with high morbidity and mortality. As the population ages, the incidence of ALI is expected to rise. Over the last decade, several studies have identified biomarkers in plasma and bronchoalveolar lavage fluid providing important insights into the mechanisms involved in the pathophysiology of ALI. Several biomarkers have been validated in subjec...

  4. Protective effect of Tetracera scandens L.leaf extract against CCl4-induced acute liver injury in rats

    Tung; Bui; Thanh; Hai; Nguyen; Thanh; Hue; Pham; Thi; Minh; Huong; Le-Thi-Thu; Huong; Duong; Thi; Ly; Loi; Vu; Duc

    2015-01-01

    Objective:To investigate the protective potential of ethanolic extracts of Tetracera scandens L.(T.scandens) against CCl4 induced oxidative stress in liver tissues.Methods:Dried leaf powder of T.scandens was extracted with ethanol and concentrated to yield a dry residue.Rats were administered with 100 mg/kg of ethanolic extracts orally once daily for one week.Animals were subsequently administered with a single dose of CCl4(I mL/kg body weight,intraperitoneal injection).Various assays,such as serum levels of alanine aminotransferase,aspartate aminotransferase,lipid peroxidation,protein oxidation(carbonyl protein group),tumor necrosis factor alpha,catalase,superoxide dismutase,and glutathione peroxidase,were used to assess damage caused by CCl4 and the protective effects of the ethanol extract on liver tissues.Results:Hepatotoxicity induced by CCl4 was evidenced by a significant increase in serum aspartate aminotransferase and alanine aminotransferase level,lipid peroxidation,protein carbonyl group,and tumor necrosis factor alpha,as well as decreased activity of the hepatic antioxidant enzymes(catalase.superoxide dismutase.and glutathione peroxidase).Treatment with ethanolic T.scandens extracts prevented all of these typically observed changes in CCl4-treated rats.Conclusions:Our findings indicate that T.scandens has a significant protective effect against CCl4 induced hepatotoxicity in rat.which may be due to its antioxidant properties.

  5. Acute kidney injury after pediatric cardiac surgery

    Sarvesh Pal Singh

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article.

  6. Acute Liver Toxicity due to Efavirenz/Emtricitabine/Tenofovir

    Rashmee Patil

    2015-01-01

    Full Text Available The fixed-dose combination of Efavirenz/Emtricitabine/Tenofovir is a first-line agent for the treatment of HIV; however few cases have reported hepatotoxicity associated with the drug. We report a case of Efavirenz/Emtricitabine/Tenofovir-associated hepatotoxicity presenting mainly with hepatocellular injury characterized by extremely elevated aminotransferase levels, which resolved without acute liver failure or need for liver transplant referral.

  7. Acute Shoulder Injuries in Adults.

    Monica, James; Vredenburgh, Zachary; Korsh, Jeremy; Gatt, Charles

    2016-07-15

    Acute shoulder injuries in adults are often initially managed by family physicians. Common acute shoulder injuries include acromioclavicular joint injuries, clavicle fractures, glenohumeral dislocations, proximal humerus fractures, and rotator cuff tears. Acromioclavicular joint injuries and clavicle fractures mostly occur in young adults as the result of a sports injury or direct trauma. Most nondisplaced or minimally displaced injuries can be treated conservatively. Treatment includes pain management, short-term use of a sling for comfort, and physical therapy as needed. Glenohumeral dislocations can result from contact sports, falls, bicycle accidents, and similar high-impact trauma. Patients will usually hold the affected arm in their contralateral hand and have pain with motion and decreased motion at the shoulder. Physical findings may include a palpable humeral head in the axilla or a dimple inferior to the acromion laterally. Reduction maneuvers usually require intra-articular lidocaine or intravenous analgesia. Proximal humerus fractures often occur in older patients after a low-energy fall. Radiography of the shoulder should include a true anteroposterior view of the glenoid, scapular Y view, and axillary view. Most of these fractures can be managed nonoperatively, using a sling, early range-of-motion exercises, and strength training. Rotator cuff tears can cause difficulty with overhead activities or pain that awakens the patient from sleep. On physical examination, patients may be unable to hold the affected arm in an elevated position. It is important to recognize the sometimes subtle signs and symptoms of acute shoulder injuries to ensure proper management and timely referral if necessary. PMID:27419328

  8. Severe but reversible acute kidney injury resulting from Amanita punctata poisoning

    Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee

    2015-01-01

    Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney i...

  9. Sleep apnea hypopnea syndrome and liver injury

    TIAN Jian-li; ZHANG Yun; CHEN Bao-yuan

    2010-01-01

    Objective A general review was made of studies involving: (1) the relationship between sleep apnea hypopneasyndrome/sleep apnea style intermittent hypoxia and liver injury and (2) the mechanism that causes the liver injury.Data sources The data used in this review were mainly from Medline and PubMed published in English from 1993 toFebruary 2009. The search term was "sleep apnea hypopnea syndrome".Study selection (1) Clinical and laboratory evidence that sleep apnea hypopnea syndrome and sleep apnea styleintermittent hypoxia leads to liver injury; (2) the mechanism that causes the liver injury.Results The effect of sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia on the liver functionis characterized by serum aminotransferase elevation. The liver histological injury includes hepatic steatosis, hepatocyteballooning, lobular inflammation, lobular necrosis, and liver fibrosis. Sleep apnea hypopnea syndrome and sleep apneastyle intermittent hypoxia can cause insulin resistance and oxidative stress.Conclusions Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can lead to chronic liverinjury, which, in most cases, is shown as nonalcoholic fatty liver disease. Insulin resistance and oxidative stress causedby sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia play an important role in the mechanismof chronic liver disease development.

  10. Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure

    Jepsen, Peter; Schmidt, Lars E; Larsen, Fin Stolze; Vilstrup, Hendrik

    2010-01-01

    Abstract Background: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure is unknown. Aim: To examine whether paracetamol-induced acute liver failure increases long-term mortality. Methods: We followed all transplant-free survivors of paracetamol-induced acute liver injury hospitalized in a Danish national referral center during 1984-2004. We compared age-specific mortality rates from one year post-discharge through 2008 between those in wh...

  11. Rapid Diagnosis of acute kidney injury (AKI) associated with cardiac surgery, using the liver type fatty acid binding protein (L-FABP) biomarker

    Mirbagheri L; Master of Biochemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran; Farhadi N; Taghipour H R; Mirbagheri M; Nourani M R

    2012-01-01

    Background and objectives: cardiac surgery is often associated with acutekidney injury (AKI). Nowadays, AKI is typically diagnosed by an increase inserum creatinine, which is a delayed and unreliable biomarker. Recent studiesrecommended using the liver type fatty acid binding protein (L-FABP) as anearly biomarker.Material and Methods: The urine samples of 18 adult patients undergoingcardiac surgery were collected in different times before (2, 4,8,24 hour) andafter cardiac surgery for detectio...

  12. Acute Kidney Injury in the Elderly

    Abdel-Kader, Khaled; Palevsky, Paul

    2009-01-01

    The aging kidney undergoes a number of important anatomic and physiologic changes that increase the risk of acute kidney injury (formerly acute renal failure) in the elderly. This article reviews these changes and discusses the diagnoses frequently encountered in the elderly patient with acute kidney injury. The incidence, staging, evaluation, management, and prognosis of acute kidney injury are also examined with special focus given to older adults.

  13. Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh.

    Guzman, Grace; Kallwitz, Eric R; Wojewoda, Christina; Chennuri, Rohini; Berkes, Jamie; Layden, Thomas J; Cotler, Scott J

    2009-01-01

    There are a growing number of cases detailing acute hepatic necrosis in patients taking black cohosh (Cimicifuga racemosa), an over-the-counter herbal supplement for management of menopausal symptoms. Our aim is to illustrate two cases of liver injury following the use of black cohosh characterized by histopathological features mimicking autoimmune hepatitis. Both patients reported black cohosh use for at least six months and had no evidence of another cause of liver disease. Their liver biopsies showed a component of centrilobular necrosis consistent with severe drug-induced liver injury. In addition, the biopsies showed characteristics of autoimmune-like liver injury with an interface hepatitis dominated by plasma cells. Although serum markers for autoimmune hepatitis were not particularly elevated, both patients responded to corticosteroids, supporting an immune-mediated component to the liver injury. Liver injury following the use of black cohosh should be included in the list of differential diagnoses for chronic hepatitis with features mimicking autoimmune hepatitis. PMID:20130783

  14. [Strategies for paediatric spleen and liver injuries].

    Zundel, S; Lieber, J; Tsiflikas, I; Henk, A-K; Schmittenbecher, P

    2014-12-01

    Traumatic injuries of the spleen and liver are typically caused by age-related falls or sports and traffic accidents. Today, the non-operative management for isolated injuries is established and evidence-based guidelines are available. The intact abdominal wall and the limited space within the peritoneum produce a compression which is the pathophysiological explanation for the limitation of the haemorrhage. Precondition for the non-operative therapy is the radiology-based classification of the injury (organ injury scale) and a haemodynamically stable patient. Haemodynamic stability is, if necessary maintained with blood transfusion, volume substitutes and the administration of catecholamines. In cases of hilar vascular injury and devascularisation or haemodynamic instability of the patient, despite utilisation of the measures mentioned above, urgent operative therapy needs to be performed. Organ sparing surgery is the therapy of choice for both liver and spleen. The spleen is required for the development of a competent immune system in the growing organism. Liver injuries can be further complicated by injury to the bile system, which might require operative reconstruction. If a patient suffers from multiple injuries and spleen or liver are involved, the decision on the management needs to be taken individually, no guidelines exist but the rate for operative therapy increases. Independent of the dimensions of injury, an experienced paediatric surgeon with his multidisciplinary team, considering the anatomic and age specific characteristics of a child, achieves the best therapeutic results. PMID:25531632

  15. Antituberculous drug-induced liver injury: current perspective.

    Devarbhavi, Harshad

    2011-01-01

    Drug-induced liver injury (DILI) is a minor but significant cause of liver injury across all regions. Antituberculosis drug-induced liver injury (TB DILI) is a leading cause of DILI and drug-induced acute liver failure (DIALF) in India and much of the developing world. Single center registries of DILI continue to highlight the high incidence of DILI and DIALF, much of it due to diagnostic errors and inappropriate prescriptions. The clinical spectrum includes asymptomatic elevation in liver tests to acute hepatitis and acute liver failure. TB DILI can occur across all age groups including children with significant morbidity and mortality. Although TB DILI develops more commonly in males, ALF is noted to be commoner in females with a worse prognosis. Contrasting reports on the role of genetic and environmental factors continue to be published. Since DILI is a diagnosis of exclusion, acute viral hepatitis particularly hepatitis E needs to be excluded in such cases. The presence of jaundice, hypoalbuminemia, ascites, encephalopathy and high prothrombin time are poor prognostic markers. Recent reports of the beneficial role of N-acetylcysteine in DIALF and in preventing TB DILI in elderly individuals needs further investigation. Reintroduction of antitubercular therapy must be balanced with the knowledge of adaptation a common occurrence with antituberculosis drugs. Although monitoring and rechallenge practices vary greatly, the importance of early clinical symptoms cannot be underestimated. Simultaneous rechallenge with combination drugs or sequential treatment have similar incidence of DILI, although increasing reports about the role of pyrazinamide in DILI and on rechallenge warrants its careful use. The combined affliction of HIV or chronic hepatitis B or C and tuberculosis poses multiple challenges including the greatly increased risks of DILI. PMID:22332331

  16. Acute liver failure and self-medication

    de OLIVEIRA, André Vitorio Câmara; ROCHA, Frederico Theobaldo Ramos; ABREU, Sílvio Romero de Oliveira

    2014-01-01

    Introduction Not responsible self-medication refers to drug use in high doses without rational indication and often associated with alcohol abuse. It can lead to liver damage and drug interactions, and may cause liver failure. Aim To warn about how the practice of self-medication can be responsible for acute liver failure. Method Were used the Medline via PubMed, Cochrane Library, SciELO and Lilacs, and additional information on institutional sites of interest crossing the headings acute live...

  17. Leptospirosis with acute liver injury

    Liu, Yong; Shores, Nathan

    2014-01-01

    A 61-year-old man with no significant medical history presented with fever, muscle pain, and weakness. He was found to be in multiorgan failure due to leptospirosis, a condition known as Weil's disease. A timely workup, combined with early initiation of antibiotics, led to effective treatment for this patient. PMID:24982581

  18. Leptospirosis with acute liver injury

    Wysocki, John; Liu, Yong; Shores, Nathan

    2014-01-01

    A 61-year-old man with no significant medical history presented with fever, muscle pain, and weakness. He was found to be in multiorgan failure due to leptospirosis, a condition known as Weil's disease. A timely workup, combined with early initiation of antibiotics, led to effective treatment for this patient.

  19. 重症急性胰腺炎大鼠肝损伤HMGB1/TLR4mRNA的表达%Changes of HMGB1 and Toll-like receptor gene expression of livers in acute liver injury complicated with severe acute pancreatitis rats

    黄鹏; 吴河水; 王春友

    2012-01-01

    目的 研究重症急性胰腺炎(SAP)大鼠肝损伤中高迁移率族蛋白B1(HMGB1)和Toll 样受体(TLR)4 mRNA的表达.方法 采用十二指肠闭襻法制作大鼠SAP模型.50只动物分为假手术组(S组)、胰腺炎组(P组).P组于建模后6、12、24、48 h分批剖杀,S组于术后6 h剖杀.观察血清淀粉酶、CRP、ALT和AST及肝组织IL-6和TNF-α的变化,RT-PCR方法检测各组不同时点肝组织HMGBl mRNA 和TLR4 mRNA的表达.结果 与S组比较,P组血清淀粉酶、CRP、ALT、AST、肝组织IL-6和TNF-α浓度升高(P<0.05).与S组比较,P组大鼠6 h肝组织TLR4 mRNA表达开始增高,术后12 h肝组织TLR4 mRNA表达迅速达到峰值(P<0.05);同时,P组HMGB1 mRNA于12 h快速上升,24~48 h时一直保持上升趋势(P<0.05);结论 SAP大鼠肝组织内HMGB1和TLR4的基因表达上调;其表达增高可能在SAP肝损伤的发生、发展中起重要作用.%Objective To investigate the changes of HMGB1 and Toll-like receptor 4 gene expression of livers in a-cute liver injury complicated with severe acute pancreatitis ( SAP ) rats. Methods Fifty SD male rats were randomly divided into Sham-operated group ( n = 10 ) and P group ( n =40 ). Levels of amylase, ALT, AST, CRP, IL-6 and TNF-α were observed. HMGB1 mRNA and TLR4 mRNA expression in the livers were measured by RT-PCR. Results Liver injuries were aggravated, the levels of serum amylase, CRP, ALT, AST, IL-6 and TNF-α were increased in livers ( P < 0.05 ). TLR4 mRNA could be detected in livers with low values in sham-operated group, but they were significantly increased at 6 hours in SAP group, peaking at 12 hours ( P <0. 05 ). HMGB1 mRNA were significantly increased at 12 hours in SAP group, peaking at 48 hours ( P <0. 05 ). Conclusion These data suggested that expression of HMGB1 mRNA and TLR4 mRNA were increased in livers in SAP, which may play an important role in mediating pro-inflammatory cytokine synthesis and release. Up-regula-tion of HMGB1 mRNA and TLR4 m

  20. Pathology of flupirtine-induced liver injury: a histological and clinical study of six cases.

    Puls, Florian; Agne, Clemens; Klein, Fritz; Koch, Martin; Rifai, Kinan; Manns, Michael P; Borlak, Jürgen; Kreipe, Hans H

    2011-06-01

    Drug-induced liver injury may cause impairment of liver function and is a leading cause of acute liver failure. Identification of the causative substance in patients receiving several drugs is often difficult in clinical practice. Evaluation of liver biopsies in suspected drug-induced injury is a challenging task that requires close clinico-pathological correlation. Recognizing a characteristic morphological pattern of liver injury may contribute to identification of the causative drug. Flupirtine, a non-opioid analgesic, has been reported to cause liver injury of idiosyncratic type in rare instances. We wished to characterize the histopathological features of flupirtine-induced liver injury, which have not been reported so far. Liver biopsies of five patients with severe liver injury and one explanted liver of a patient with flupirtine-induced acute liver failure that required transplantation were assessed. In addition clinical presentation and course were reviewed and clinical follow up was performed. Extensive perivenular necrosis with associated ceroid pigment-laden macrophages and a mild to moderate lymphocytic infiltrate was a common feature in all cases. Histological extent of liver necrosis corresponded well to serum amino-transferase levels. Accidental reexposure of one patient resulted in a plasma cell rich hepatitis with perivenular necrosis. This study provides evidence that flupirtine can cause substantial liver injury of hepatocellular type. Liver damage is associated with a characteristic morphological picture, the recognition of which will aid in causality assessment of drug-induced liver injury. Clinical and histological features raise the possibility of an immune-mediated toxicity. PMID:21590308

  1. The cell cycle and acute kidney injury

    Price, Peter M.; Safirstein, Robert L.; Megyesi, Judit

    2009-01-01

    Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used to control and perhaps to prevent acute kidney injury. This review is written to address the correlation between cellular life and death in kidney tubules, especially in acute ki...

  2. Pregnancy related acute kidney injury: nondialytic management

    Kaliki Hymavathi Reddy

    2015-04-01

    Full Text Available Acute Kidney Injury (AKI is associated with increased mortality and morbidity unless timely diagnosed and promptly managed. An understanding of the renal physiologic changes that occur during pregnancy is essential for Proper evaluation, diagnosis, and management of Pregnancy Related AKI (PRAKI. In the general population, AKI can occur from prerenal, intrinsic/renal, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management and prevention of adverse maternal/fetal outcomes. Sometimes PRAKI may require intensive management and even dialysis adding additional economical burden to the patient. We here, with report an interesting case of PRAKI diagnosed and managed in time by simple medical measures thus delivering an effective treatment at a much lesser cost. [Int J Reprod Contracept Obstet Gynecol 2015; 4(2.000: 486-489

  3. Comparative gene and protein expression analyses of a panel of cytokines in acute and chronic drug-induced liver injury in rats

    Drug-induced liver injury (DILI) is a significant safety issue associated with medication use, and is the major cause of failures in drug development and withdrawal in post marketing. Cytokines are signaling molecules produced and secreted by immune cells and play crucial roles in the progression of DILI. Although there are numerous reports of cytokine changes in several DILI models, a comprehensive analysis of cytokine expression changes in rat liver injury induced by various compounds has, to the best of our knowledge, not been performed. In the past several years, we have built a public, free, large-scale toxicogenomics database, called Open TG-GATEs, containing microarray data and toxicity data of the liver of rats treated with various hepatotoxic compounds. In this study, we measured the protein expression levels of a panel of 24 cytokines in frozen liver of rats treated with a total of 20 compounds, obtained in the original study that formed the basis of the Open TG-GATEs database and analyzed protein expression profiles combined with mRNA expression profiles to investigate the correlation between mRNA and protein expression levels. As a result, we demonstrated significant correlations between mRNA and protein expression changes for interleukin (IL)-1β, IL-1α, monocyte chemo-attractant protein (MCP)-1/CC-chemokine ligand (Ccl)2, vascular endothelial growth factor A (VEGF-A), and regulated upon activation normal T cell expressed and secreted (RANTES)/Ccl5 in several different types of DILI. We also demonstrated that IL-1β protein and MCP-1/Ccl2 mRNA were commonly up-regulated in the liver of rats treated with different classes of hepatotoxicants and exhibited the highest accuracy in the detection of hepatotoxicity. The results also demonstrate that hepatic mRNA changes do not always correlate with protein changes of cytokines in the liver. This is the first study to provide a comprehensive analysis of mRNA–protein correlations of factors involved in

  4. Transfusion related acute lung injury

    Sharma Ratti; Bhattacharya Prasun; Thakral Beenu; Saluja Karan; Marwaha Neelam

    2009-01-01

    Transfusion related acute lung injury (TRALI) is an uncommon but potentially fatal adverse reaction to transfusion of plasma containing blood components. We describe a case of 10-year-old male child with aplastic anemia, platelet count of 7800/΅l, B positive blood group who developed fever (39.2΀C), difficulty in breathing and cyanosis within 2 hrs after transfusion of a random platelet concentrate. Despite the best resuscitative efforts, the child died within next 24 hrs. The prese...

  5. Exenatide induced acute kidney injury.

    Aijazi, Ishma; Abdulla, Fadhil M; Zuberi, Beyla J; Elhassan, Ahmed

    2014-01-01

    Exenatide is an incretin mimetic. It was approved by the federal drug authority in 2005 for the treatment of type-2 diabetes. Since it is a relatively new medicine clinicians have limited experience with regards to its side effects and safety profile. We report a 47 year old lady who presented with exenatide associated acute kidney injury. She had type-2 diabetes for 10 years with mild micro albuminuria and normal renal functions. She was also taking a stable dose of metformin, gliclazide, angiotensin converting enzyme inhibitor and diuretic for over a year and there was no history of any recent use of non-steroid anti-inflammatory medications. One week after starting exenatide, she developed severe vomiting, followed by hypotension. She presented with acute renal insufficiency and severe lactic acidosis and had to be dialyzed on emergency basis. To our knowledge this is probably the first case reported in the local United Arab Emirate (U.A.E) population. PMID:25672206

  6. MicroRNA-674-5p/5-LO axis involved in autoimmune reaction of Concanavalin A-induced acute mouse liver injury.

    Su, Kunkai; Wang, Qi; Qi, Luoyang; Hua, Dasong; Tao, Jingjing; Mangan, Connor J; Lou, Yijia; Li, Lanjuan

    2016-09-01

    Autoimmune hepatitis is characterized, in part, by the pathways involving cysteinyl-leukotriene metabolites of arachidonic acid, the dynamics of which remain unclear. Here, we explored post-transcriptional regulation in the 5-lipoxygenase (5-LO) pathway of arachidonic acid in a Concanavalin A (Con A) induced mouse model. We found that Con A administration lead to 5-LO overexpression and cysteinyl-leukotriene release in early hepatic injury, which was attenuated by cyclosporin A pretreatment. Subsequent microarray and qRT-PCR analysis further showed that microRNA-674-5p (miR-674-5p) displayed a significant decrease in expression in Con A-damaged liver. Noting that miR-674-5p harbors a potential binding region for 5-LO, we further transfected hepatic cell lines with overexpressing miR-674-5p mimic and discovered a negative regulating effect of miR-674-5p on 5-LO expression in the presence of IL-6 or TNF-α. These findings suggest that miR-674-5p might be a negative regulator in 5-LO mediated autoimmune liver injury, representing a compelling avenue towards future therapeutic interventions. PMID:27313091

  7. Chikusetsusaponin V attenuates lipopolysaccharide-induced liver injury in mice.

    Dai, Yan Wen; Zhang, Chang Cheng; Zhao, Hai Xia; Wan, Jing Zhi; Deng, Li Li; Zhou, Zhi Yong; Dun, Yao Yan; Liu, Chao Qi; Yuan, Ding; Wang, Ting

    2016-06-01

    Chikusetsusaponin V (CsV), a saponin from Panax japonicus, has been reported to inhibit inflammatory responses in lipopolysaccharide (LPS)-induced macrophage cells. However, whether CsV could alleviate LPS-induced liver injury in vivo and the potential mechanisms involved remain unclear. In the present study, we investigated the anti-inflammatory effects of CsV on LPS-induced acute liver injury in mice and further explored the potential mechanisms involved. Our results showed that CsV significantly attenuated elevation of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels and improved liver histopathological changes in LPS-induced mice. In addition, CsV decreased serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), TNF-α and IL-1β in LPS challenged mice. Furthermore, CsV inhibited nuclear factor kappa B (NF-κB) activation by downregulating phosphorylated NF-κB, IκB-α, ERK, c-Jun N-terminal kinase (JNK) and p38 levels in the liver tissue, which ultimately decreased nucleus NF-κB protein level. In conclusion, our data suggested that CsV could be a promising drug for preventing LPS challenged liver injury since it attenuated LPS-induced inflammatory responses, partly via inhibiting NF-κB and MAPK signaling pathways. PMID:26981791

  8. The Pathology of Acute Liver Failure.

    Lefkowitch, Jay H

    2016-05-01

    Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells. This paper reviews the liver pathology in ALF, including forms of zonal necrosis and their etiologies. PMID:27058243

  9. An Update on Drug-induced Liver Injury.

    Devarbhavi, Harshad

    2012-09-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of

  10. [Acute liver failure after ingestion of death cap mushrooms].

    Zuliani, Anna-Maria; Kabar, Iyad; Mitchell, Todd; Heinzow, Hauke Sebastian

    2016-07-01

    Amatoxins, which are mainly found in Amanita phalloides, Amanita virosa, and Galerina autumnalis, are responsible for the majority of fatal intoxication with green death cap. The intoxication is associated with acute liver failure, which explains the poor prognosis. Acute liver injury is generally preceeded by a gastrointestinal phase with nausea, vomiting and diarrhea. In the course, pre-renal kidney failure due to the associated fluid deficit and fulminant liver failure may occur. General guidelines for the treatment of amatoxin poisoning are yet not available. We report on three patients who suffered from amatoxin mushroom poisoning after ingestion of green death cap mushrooms. Based on the pathophysiology of amatoxin poisoning, we discuss a potential therapeutic approach. PMID:27359312

  11. Research status of the mechanism and treatment for acute pancreatitis complicated with hepatic injury

    Xiping Zhang; Jie Zhang; Ping Yang

    2008-01-01

    Acute pancreatitis(AP) is characterized by its sudden onset and rapid progression and is often complicated by liver injury. AP induced liver injury may develop into hepatic failure and even result in death. Thus, it is of importance to protect liver function and block injury-related pathways. In the pathogenesis of liver injury in AP, inflammatory cytokines, nuclear factor-kappa B(NF- K B) and oxygen free radicals play important roles. The complexity of the mechanism underlying the development of liver injury exerts, to some extent, a contribution to the difficulties in the treatment of this disease. Currently, the drugs used to treat the disease include L-arginine (L-Arg),calcium ion antagonists, somatostatin and a variety of inflammatory mediator inhibitors. Additionally, some traditional Chinese medicines such as tfipterygium, wiifordii, rhubarb and salvia miltiorrhizae may also have some effects. In this article, the pathogenesis of liver injury in AP and its therapy are reviewed.

  12. Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells in acute liver injured mice.

    Peng, Yuan; Chen, Qian; Yang, Tao; Tao, Yanyan; Lu, Xiong; Liu, Chenghai

    2014-03-01

    Cultured mycelium Cordyceps sinensis (CMCS) was widely used for a variety of diseases including liver injury, the current study aims to investigate the protective effects of CMCS on liver sinusoidal endothelial cells (LSECs) in acute injury liver and related action mechanisms. The mice were injected intraperitoneally with lipopolysaccharide (LPS) and D-galactosamine (D-GalN). 39 male BABL/c mice were randomly divided into four groups: normal control, model control, CMCS treatment and 1,10-phenanthroline treatment groups. The Serum liver function parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were assayed with the commercial kit. The inflammation and scaffold structure in liver were stained with hematoxylin and eosin and silver staining respectively. The LSECs and sub-endothelial basement membrane were observed with the scanning and transmission electronic microscope. The protein expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in liver were analyzed with Western blotting. Expression of von Willebrand factor (vWF) was investigated with immunofluorescence staining. The lipid peroxidation indicators including antisuperoxideanion (ASAFR), hydroxyl free radical (·OH), superoxide dismutase (SOD), malondialdehyde and glutathione S-transferase (GST) were determined with kits, and matrix metalloproteinase-2 and 9 (MMP-2/9) activities in liver were analyzed with gelatin zymography and in situ fluorescent zymography respectively. The model mice had much higher serum levels of ALT and AST than the normal mice. Compared to that in the normal control, more severe liver inflammation and hepatocyte apoptosis, worse hepatic lipid peroxidation demonstrated by the increased ASAFR, ·OH and MDA, but decreased SOD and GST, increased MMP-2/9 activities and VCAM-1, ICAM-1 and vWF expressions, which revealed obvious LSEC injury and scaffold structure broken, were shown in the model

  13. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians

  14. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents: A Case Report.

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians should rule

  15. Clinical heterogeneity in autoimmune acute liver failure

    Norberto C Chavez-Tapia; Julio Martinez-Salgado; Julio Granados; Misael Uribe; Felix I Tellez-Avila

    2007-01-01

    AIM:To describe the outcome and prognosis in a cohort of patients with acute liver failure due to autoimmune hepatitis without liver transplantation.METHODS:A retrospective trial was conducted in 11 patients with acute liver failure due to autoimmune hepatitis who attended the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran. Demographic,biochemical and severity indexes,and treatment and outcome were assessed.RESULTS: Among the 11 patients, with a median age of 31 years, 72% had inflammatory response syndrome, and six patients received corticosteroids.The mortality rate within four weeks was 56%, and the one-year survival was 27%. In the survivors, severity indexes were lower and 83% received corticosteroids.CONCLUSION:We observed a relatively high survival rate in patients with acute liver failure due to autoimmune hepatitis. This survival rate could be influenced by severity of the disease and/or use of corticosteroids.

  16. Liver injury in invasive aspergillus. Echographic findings

    Aspergillus is the second most common mycoses in immuno compromised patients. The invasive form is associated with a mortality of approximately 100%. We present a case of invasive aspergillus in a heart transplant recipient in whom ultrasound disclosed the presence of liver injury which was later confirmed by necropsy. We review the available literature. (Author) 15 refs

  17. Expression of ECM proteins fibulin-1 and -2 in acute and chronic liver disease and in cultured rat liver cells

    Piscaglia, Fabio; Dudás, József; Knittel, Thomas; Rocco, Paola; Kobold, Dominik; Saile, Bernhard; Zocco, Maria; Timpl, Rupert; Ramadori, Giuliano

    2009-01-01

    Fibulin-2 has previously been considered as a marker to distinguish rat liver myofibroblasts from hepatic stellate cells. The function of other fibulins in acute or chronic liver damage has not yet been investigated. The aim of this study has been to evaluate the expression of fibulin-1 and -2 in models of rat liver injury and in human liver cirrhosis. Their cellular sources have also been investigated. In normal rat liver, fibulin-1 and -2 were both mainly present in the portal field. Fibuli...

  18. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital

    Mrzljak, Anna; Kosuta, Iva; Skrtic, Anita; Kanizaj, Tajana Filipec; Vrhovac, Radovan

    2013-01-01

    Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both ...

  19. The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

    Jeschke, Marc G.

    2009-01-01

    Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury....

  20. Transfusion related acute lung injury

    Sharma Ratti

    2009-10-01

    Full Text Available Transfusion related acute lung injury (TRALI is an uncommon but potentially fatal adverse reaction to transfusion of plasma containing blood components. We describe a case of 10-year-old male child with aplastic anemia, platelet count of 7800/΅l, B positive blood group who developed fever (39.2΀C, difficulty in breathing and cyanosis within 2 hrs after transfusion of a random platelet concentrate. Despite the best resuscitative efforts, the child died within next 24 hrs. The present case highlights the fact that TRALI should be kept as a differential diagnosis in all patients developing acute respiratory discomfort within 6 hrs of transfusion. Without a ′gold standard′ the diagnosis of TRALI relies on a high index of suspicion and on excluding other types of transfusion reactions. Notification to transfusion services is crucial to ensure that a proper investigation is carried out and at-risk donor and recipients can be identified, and risk reduction measures can be adopted.

  1. Nephrology Update: Acute Kidney Injury.

    Sarabu, Nagaraju; Rahman, Mahboob

    2016-05-01

    Acute kidney injury (AKI) refers to any acute decrease in glomerular filtration rate, regardless of etiology. Staging of AKI has been recommended to stratify AKI patients according to severity of the condition, based on serum creatinine level and urine output. Classification of AKI into prerenal, intrinsic renal, and postrenal etiologies is helpful in differential diagnosis and management. AKI in hospitalized patients typically occurs due to decreased renal perfusion. Drug-induced, contrast-associated, postoperative, and sepsis-associated AKI also can occur. Clinical assessment of a patient with AKI involves a medical record review, thorough history and physical examination, urinary and blood tests, renal imaging, and, in some instances, renal biopsy. Contrast-induced nephropathy is a common iatrogenic etiology of AKI associated with administration of intravenous iodinated contrast media. Measures to prevent AKI should be taken before administration of intravenous iodinated contrast. AKI can result in many short- and long-term complications, including chronic kidney disease and end-stage renal disease. Appropriate treatment of AKI patients involves management of the underlying etiology, when possible, and use of nondialytic and dialytic therapies. PMID:27163760

  2. Disseminated tuberculosis presenting as acute lung injury

    Mary Grace

    2014-01-01

    Full Text Available Tuberculosis presenting as acute lung injury is distinctly uncommon, even in India where tuberculosis an endemic disease. Simultaneously, acute lung injury is a highly fatal complication of tuberculosis. A high index of suspicion is needed to diagnose tuberculosis in such cases. Failure to initiate early treatment can have disastrous consequences as exemplified in this case report. This case attempts to highlight the need to consider tuberculosis as one of the likely causative factors for acute lung injury and the importance of starting empirical antituberculous therapy in suspected cases early.

  3. Transfusion-related acute lung injury: incidence and risk factors

    Toy, Pearl; Gajic, Ognjen; Bacchetti, Peter; Looney, Mark R.; Gropper, Michael A.; Hubmayr, Rolf; Lowell, Clifford A.; Norris, Philip J; Murphy, Edward L; Weiskopf, Richard B.; Wilson, Gregory; Koenigsberg, Monique; Lee, Deanna; Schuller, Randy; Wu, Ping

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current s...

  4. Transfusion-related acute lung injury: Incidence and risk factors

    Toy, P; Gajic, O; Bacchetti, P; Looney, MR; Gropper, MA; Hubmayr, R; Lowell, CA; Norris, PJ; Murphy, EL; Weiskopf, RB; Wilson, G; Koenigsberg, M; Lee, D.; Schuller, R.; Wu, P.

    2011-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion- related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current ...

  5. Acute myopathy associated with liver cirrhosis

    Ok-Jae Lee; Jee-Hyang Yoon; Eun-Jeong Lee; Hyun-Jin Kim; Tae-Hyo Kim

    2006-01-01

    AIM: Many cirrhotic patients have muscular symptoms and rhabdomyolysis. However, myopathy associated with liver cirrhosis has not been established as a disease entity. We evaluated the clinical significance of acute myopathy associated with liver cirrhosis.METHODS: We retrospectively reviewed the medical records of 5440 cirrhotic patients who had been admitted to Gyeongsang National University Hospital from August 1997 to January 2003. Among these, 99 developed acute myopathies, and they were analyzed with respect to clinical and laboratory parameters, and outcomes.RESULTS: The Child-Pugh classification at the time of myopathy onset was A in 3(3.1%) cases, B in 33(33.3%), and C in 63 (63.6%). Infection was identified as the most predisposing factor to myopathy. Fifty percent of 18 idiopathic cases who were tested for influenza antibody were positive. Forty-two of the 99 cases were complicated by acute renal failure, and 25 (59.5%) of these expired. Apart from 6 cases lost to follow-up, 64 of 93 recovered, giving a mortality rate of 31.2%. Mortality was higher in Child-Pugh class C than in B or A.CONCLUSION: Acute myopathy can develop as a serious complication in liver cirrhosis. Its frequency, severity and mortality depend on underlying liver function, and are higher in decompensated liver cirrhosis. Influenza should be considered as an etiologic factor in idiopathic cases. It is proposed that acute myopathy associated with liver cirrhosis be called 'hepatic myopathy', and that careful monitoring for hepatic myopathy is necessary in the patients with advanced liver cirrhosis.

  6. Dengue fever with acute liver failure

    Vinodh B

    2005-01-01

    Full Text Available A virus belonging to the Flaviviridae group causes dengue haemorrhagic fever. Dengue presenting as acute liver failure is rare. Dengue is endemic in India. The last epidemic of dengue occurred in Delhi in 2003. During this epidemic, 2185 confirmed cases of dengue were reported. Dengue virus serotypes 2 and 3 were responsible for this epidemic. A 19-yr-old male presented to our hospital with the complaints of fever for 12 days, during this epidemic. He was diagnosed as having dengue shock syndrome, stage IV with acute liver failure. He had primary dengue infection. He made complete recovery with supportive management.

  7. Activation and Regulation of Hemostasis in Acute Liver Failure and Acute Pancreatitis

    Lisman, Ton; Porte, Robert J.

    2010-01-01

    Acute liver failure and acute pancreatitis are accompanied by substantial changes in the hemostatic system. In acute liver failure, defective synthesis of coagulation factors and intravascular activation of coagulation results in thrombocytopenia and reduced levels of proteins involved in coagulatio

  8. Portal hypertension in acute liver failure.

    3.M. Navasa; Garcia-Pagán, J C; Bosch, J; Riera, J R; R. Bañares; Mas, A.; Bruguera, M; Rodés, J

    1992-01-01

    Twenty five patients with acute liver failure were measured for hepatic venous pressure gradient as an index of portal pressure during the course of a transjugular liver biopsy. Hepatic venous pressure gradient ranged from 4 to 24.5 mm Hg with a mean of 12.8 (5.3) mm Hg (normal values less than 5 mm Hg). All patients but one had increased portal pressure gradient. Portal hypertension correlated with the degree of architectural distortion of the liver, as suggested by a direct correlation betw...

  9. Disseminated tuberculosis presenting as acute lung injury

    Mary Grace; V K Shameer; Renjith Bharathan; Kavitha Chandrikakumari

    2014-01-01

    Tuberculosis presenting as acute lung injury is distinctly uncommon, even in India where tuberculosis an endemic disease. Simultaneously, acute lung injury is a highly fatal complication of tuberculosis. A high index of suspicion is needed to diagnose tuberculosis in such cases. Failure to initiate early treatment can have disastrous consequences as exemplified in this case report. This case attempts to highlight the need to consider tuberculosis as one of the likely causative factors for acu...

  10. Novel Imaging Techniques in Acute Kidney Injury

    Kalantarinia, Kambiz

    2009-01-01

    Imaging of the kidneys can provide valuable information in the work up and management of acute kidney injury. Several different imaging modalities are used to gather information on anatomy of the kidney, to rule out obstruction, differentiate acute kidney injury (AKI) and chronic kidney disease and to obtain information on renal blood flow and GFR. Ultrasound is the most widely used imaging modality used in the initial work up of AKI. The utility of contrast enhanced computerized tomography a...

  11. Tetrahydroxystilbene glucoside protects against ethanol-induced liver injury in mice by inhibition of expression of inflammatuion-related factors

    熊章鄂

    2013-01-01

    Objective To investigate the protective effects of tetrahydroxystilbene glucoside(TSG)against acute ethanol-induced liver injury in mice and to explore the possible mechanisms involved.Methods Kunming mice were

  12. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder

    Miguel Bispo; Ana Valente; Rosário Maldonado; Rui Palma; Helena Glória; Jo(a)o Nóbrega; Paula Alexandrino

    2009-01-01

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.

  13. [Perioperative acute kidney injury and failure].

    Chhor, Vibol; Journois, Didier

    2014-04-01

    Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance. PMID:24656890

  14. Management of acute spinal cord injury.

    Wagner, F C

    1977-06-01

    Based on the experience with 58 patients with acute spinal cord injuries, a system for rapidly evaluating such patients has been developed. With the knowledge that has been acquired clinically and experimentally of spinal cord injury and with the information provided by laminography and by either air or Pantopaque myelography, a reasonably certain diagnosis of the type of spinal cord injury may be made. Treatment designed to restore neurological function may then be instituted promptly. PMID:882906

  15. Pathogenesis of acute lung injury in severe acute pancreatitis

    SHI Lei; YUE Yuan; ZHANG Mei; PAN Cheng-en

    2005-01-01

    Objective:To study the pathogenesis of acute lung injury in severe acute pancreatitis (SAP). Methods:Rats were sacrificed at 1, 3, 5, 6, 9 and 12 h after establishment of inducing model. Pancreas and lung tissues were obtained for pathological study, microvascular permeability and MPO examination. Gene expressions of TNF-α and ICAM-1 in pancreas and lung tissues were detected by RT-PCR. Results:After inducing SAP model, the injury degree of the pancreas and the lung increased gradually, accompanied with gradually increased MPO activity and microvascular permeability. Gene expressions of TNF-α and ICAM-1 in pancreas rose at 1 h and reached peak at 7 h. Relatively, their gene expressions in the lungs only rose slightly at 1 h and reached peak at 9-12 h gradually. Conclusion:There is an obvious time window between SAP and lung injury, when earlier protection is beneficial to prevent development of acute lung injury.

  16. Acute pulmonary injury: high-resolution CT and histopathological spectrum

    Obadina, E T; Torrealba, J M; Kanne, J P

    2013-01-01

    Acute lung injury usually causes hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS). Although diffuse alveolar damage is the hallmark of ARDS, other histopathological patterns of injury, such as acute and fibrinoid organising pneumonia, can be associated with acute respiratory failure. Acute eosinophilic pneumonia can also cause acute hypoxaemic respiratory failure and mimic ARDS. This pictorial essay reviews the high-resolution CT findings of acute lung injury and ...

  17. ACUTE APENDICITIS IN LIVER TRANSPLANT RECIPIENTS

    da FONSECA-NETO, Olival Cirilo Lucena; LIMA, Heloise Caroline de Souza; de MELO, Paulo Sérgio Vieira; LEMOS, Roberto; LEITÃO, Laércio; AMORIM, Américo Gusmão; LACERDA, Cláudio Moura

    2016-01-01

    Background : Appendicitis is a common cause of emergency surgery that in the population undergoing organ transplantation presents a rare incidence due to late diagnosis and treatment. Aim : To report the occurrence of acute appendicitis in a cohort of liver transplant recipients. Methods : Retrospective analysis in a period of 12 years among 925 liver transplants, in witch five cases of acute appendicitis were encountered. Results : Appendicitis occurred between three and 46 months after liver transplantation. The age ranged between 15 and 58 years. There were three men and two women. The clinical presentations varied, but not discordant from those found in non-transplanted patients. Pain was a symptom found in all patients, in two cases well located in the right iliac fossa (40%). Two patients had symptoms characteristic of peritoneal irritation (40%) and one patient had abdominal distention (20%). All patients were submitted to laparotomies. In 20% there were no complications. In 80% was performed appendectomy complicated by suppuration (40%) or perforation (40%). Superficial infection of the surgical site occurred in two patients, requiring clinical management. The hospital stay ranged from 48 h to 45 days. Conclusion : Acute appendicitis after liver transplantation is a rare event being associated with a high rate of drilling, due to delays in diagnosis and therapy, and an increase in hospital stay. PMID:27120736

  18. Acute-on-chronic liver failure: a review

    Zamora Nava LE

    2014-04-01

    Full Text Available Luis Eduardo Zamora Nava,1 Jonathan Aguirre Valadez,2 Norberto C Chávez-Tapia,3 Aldo Torre21Department of Endoscopy, 2Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 3Obesity and Digestive Diseases Unit, Medica Sur Clinic and Foundation, Mexico City, MexicoAbstract: There is no universally accepted definition of acute-on-chronic liver failure; however, it is recognized as an entity characterized by decompensation from an underlying chronic liver disease associated with organ failure that conveys high short-term mortality, with alcoholism and infection being the most frequent precipitating events. The pathophysiology involves inflammatory processes associated with a trigger factor in susceptible individuals (related to altered immunity in the cirrhotic population. This review addresses the different definitions developed by leading research groups, epidemiological and pathophysiological aspects, and the latest treatments for this entity.Keywords: acute-on-chronic liver failure, cirrhosis, organ failure, acute kidney injury, infection

  19. Montelukast-induced acute fulminant liver failure: A case report

    ÇELİK, Mustafa; Arabul, Mahmut; Alper, Emrah; CANTÜRK, Fatih; KANDEMİR, Altay; Vatansever, Sezgin; Ünsal, Belkıs

    2012-01-01

    Drug-induced liver injury is commonly encountered in general practice and a potential complication of many medications. Hepatotoxicity associated with montelukast-induced liver injury including elevated liver tests, hepatitis and fulminant liver failure has been described with rare case reports. We present the case of a 42-year-old woman with montelukast-induced fulminant liver failure. A 42-year-old woman had been taking salbutamol inhaler and salmeterol + fluticasone inhaler for five y...

  20. Acute kidney injury and rhabdomyolysis due to multiple wasp stings

    Hemachandar Radhakrishnan

    2014-01-01

    In most patients, wasp stings cause local reactions and rarely anaphylaxis. Acute kidney injury and rhabdomyolysis are unusual complications of wasp stings. We report a case of acute kidney injury and rhabdomyolysis secondary to multiple wasp stings. A 55-year-old farmer developed multi organ dysfunction with acute kidney injury and rhabdomyolysis 3 days after he had sustained multiple wasp stings. The etiology of acute kidney injury is probably both rhabdomyolysis and acute tubular necrosis....

  1. Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

    van de Poll, Marcel C. G.; Derikx, Joep P. M.; Buurman, Wim A.; Peters, Wilbert H. M.; Hennie M J Roelofs; Stephen J Wigmore; Dejong, Cornelis H C

    2007-01-01

    BACKGROUND:Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection.METHODS:Markers of hepatocyte injury (AST, GSTalpha, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with ...

  2. Preditores de injúria renal aguda em pacientes submetidos ao transplante ortotópico de fígado convencional sem desvio venovenoso Predictors of acute kidney injury in patients undergoing a conventional orthotopic liver transplant without veno-venous bypass

    Olival Cirilo L. da Fonseca-Neto

    2011-06-01

    Full Text Available RADICAL: Injúria renal aguda é uma das complicações mais comuns do transplante ortotópico de fígado. A ausência de critério universal para sua definição nestas condições dificulta as comparações entre os estudos. A técnica convencional para o transplante consiste na excisão total da veia cava inferior retro-hepática durante a hepatectomia nativa. Controvérsias sobre o efeito da técnica convencional sem desvio venovenoso na função renal continuam. OBJETIVO: Estimar a incidência e os fatores de risco de injúria renal aguda entre os receptores de transplante ortotópico de fígado convencional sem desvio venovenoso. MÉTODOS: Foram avaliados 375 pacientes submetidos a transplante ortotópico de fígado. Foram analisadas as variáveis pré, intra e pós-operatórias em 153 pacientes submetidos a transplante ortotópico de fígado convencional sem desvio venovenoso. O critério para a injúria renal aguda foi valor da creatinina sérica > 1,5 mg/dl ou débito urinário BACKGROUND: Acute kidney injury is one of the most common complications of orthotopic liver transplantation. The absence of universal criteria for definition of these conditions make comparisons difficult between studies. The conventional technique for transplantation is the total excision of the inferior vena cava during liver retro-native hepatectomy. Controversies about the effect of the conventional technique without venovenous bypass on renal function remain. AIM: To estimate the incidence and risk of acute kidney injury factors among recipients of orthotopic liver transplantation without conventional venovenous bypass. METHODS: Was studied 375 patients undergoing orthotopic liver transplantation. Variables were analyzed in preoperative, intraoperative and postoperative complications in 153 patients undergoing orthotopic liver transplantation without conventional venovenous bypass. The criterion for acute kidney injury was serum creatinine > 1.5 mg/dl or

  3. Quercetin prevents pyrrolizidine alkaloid clivorine-induced liver injury in mice by elevating body defense capacity.

    Lili Ji

    Full Text Available Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin.

  4. Autophagy and ethanol-induced liver injury

    Terrence M Donohue Jr

    2009-01-01

    The majority of ethanol metabolism occurs in the liver. Consequently, this organ sustains the greatest damage from ethanol abuse. Ethanol consumption disturbs the delicate balance of protein homeostasis in the liver, causing intracellular protein accumulation due to a disruption of hepatic protein catabolism.Evidence indicates that ethanol or its metabolism impairs trafficking events in the liver, including the process of macroautophagy, which is the engulfment and degradation of cytoplasmic constituents by the lysosomal system. Autophagy is an essential, ongoing cellular process that is highly regulated by nutrients,endocrine factors and signaling pathways. A great number of the genes and gene products that govern the autophagic response have been characterized and the major metabolic and signaling pathways that activate or suppress autophagy have been identified. This review describes the process of autophagy, its regulation and the possible mechanisms by which ethanol disrupts the process of autophagic degradation. The implications of autophagic suppression are discussed in relation to the pathogenesis of alcohol-induced liver injury.

  5. Acute renal dysfunction in liver diseases

    2007-01-01

    Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (MRS) is a unique form of renal failure associated with advanced liver disease or cirrhosis, and is characterized by functional renal impairment without significant changes in renal histology. Irrespective of the type of renal failure, renal hypoperfusion is the central pathogenetic mechanism, due either to reduced perfusion pressure or increased renal vascular resistance. Volume expansion, avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment. Splanchnic vasoconstrictor agents, such as terlipressin, along with volume expansion, and early placement of transjugular intrahepatic portosystemic shunt (TIPS) may be effective in improving renal function in HRS. Continuous renal replacement therapy (CRRT) and molecular absorbent recirculating system (MARS) in selected patients may be life saving while awaiting liver transplantation.

  6. Prognostic models for acute liver failure

    Wei-Bo Du; Xiao-Ping Pan; Lan-Juan Li

    2010-01-01

    BACKGROUND: Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES: Five English-language medical databases, MEDLINE, ScienceDirect, OVID, Springer Link and Wiley Interscience were searched for articles on"acute liver failure","prognosis", and related topics. RESULTS: Multi-variable prognostic models including the King's College Hospital criteria and the model for end-stage liver disease score have been widely used in determination of the prognosis of ALF, but the results are far from satisfactory. Other prognostic indicators including serum Gc-globulin, arterial blood lactate, serum phosphate, arterial blood ammonia, and serum alpha-fetoprotein are promising but await further assessement. CONCLUSIONS: A reliable prognostic model to be developed in the future should not only have predictive value for poor outcome but also help to predict the survival of patients without a liver transplantation. Further studies are necessary to assess the prognostic accuracy of any new models.

  7. Acute Hydrocephalus Following Cervical Spinal Cord Injury

    Son, Seong; Lee, Sang Gu; Park, Chan Woo; Kim, Woo Kyung

    2013-01-01

    We present a case of acute hydrocephalus secondary to cervical spinal cord injury in a patient with diffuse ossification of the posterior longitudinal ligament (OPLL). A 75-year-old male patient visited the emergency department with tetraparesis and spinal shock. Imaging studies showed cervical spinal cord injury with hemorrhage and diffuse OPLL from C1 to C4. We performed decompressive laminectomy and occipitocervical fusion. Two days after surgery, his mental status had deteriorated to drow...

  8. First Aid for Acute Sports Injuries

    Bull, R.C.

    1987-01-01

    This article deals with management of acute sports injuries on the field or on the ice and in the dressing room or in the arena's first-aid room. Its most vital message is “Be prepared”. A team approach and suitable ambulance and hospital back-up are mandatory. Individual management of a specific acute injury should be approached with a practice plan. Collars, splints, back board, doctor's bag, ambu bag, suture tray and emergency medications should be at hand. Care must be taken that no long-...

  9. Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome

    Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Paul R. Knight; Notter, Robert H.

    2008-01-01

    Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, a...

  10. Analysis of 133 patients with severe blunt liver injury

    2001-01-01

    Objective: To investigate the treatment and causes of death aboutsevere blunt liver injury.Methods: The data of 133 patients with severe blunt liver injury (Grade Ⅲ to Grade Ⅴ) were analyzed retrospectively. All the patients except 2 underwent operations. Different types of surgical procedures were adopted according to the severity of liver injury.Results: Operations were the major method to treat hepatic injury. The total mortality rate was 21.0% in this study. The mortality rates of Grade Ⅲ, Grade Ⅳ and Grade Ⅴ of liver injuries were 11.3%, 24.4% and 69.2%, respectively.Conclusions: Packing treatment plays an important role in the treatment of hepatic injury. The mortality rate is related closely to the severity of hepatic injury, multiple trauma, shock and disturbance of blood coagulation.

  11. Transfusion related acute lung injury (TRALI)

    TAJANA ZAH; JASNA MESARIC; VISNJA MAJERIC-KOGLER

    2009-01-01

    Transfusion-related acute lung injury (TRALI) is a complication following transfusion of blood products and is potentially a life-threatening adverse event of transfusion. The first case of fatal pulmonary edema following transfusion was reported in the 1950s. In recent time, TRALI has developed from an almost unknown transfusion reaction to the most common cause of transfusion related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute res...

  12. Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury.

    Yao, Lu; Chen, Weina; Han, Chang; Wu, Tong

    2016-06-01

    Microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme for the synthesis of prostaglandin E2 (PGE2), a proproliferative and antiapoptotic lipid molecule important for tissue regeneration and injury repair. In this study, we developed transgenic (Tg) mice with targeted expression of mPGES-1 in the liver to assess Fas-induced hepatocyte apoptosis and acute liver injury. Compared with wild-type (WT) mice, the mPGES-1 Tg mice showed less liver hemorrhage, lower serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, less hepatic necrosis/apoptosis, and lower level of caspase cascade activation after intraperitoneal injection of the anti-Fas antibody Jo2. Western blotting analysis revealed increased expression and activation of the serine/threonine kinase Akt and associated antiapoptotic molecules in the liver tissues of Jo2-treated mPGES-1 Tg mice. Pretreatment with the mPGES-1 inhibitor (MF63) or the Akt inhibitor (Akt inhibitor V) restored the susceptibility of the mPGES-1 Tg mice to Fas-induced liver injury. Our findings provide novel evidence that mPGES-1 prevents Fas-induced liver injury through activation of Akt and related signaling and suggest that induction of mPGES-1 or treatment with PGE2 may represent important therapeutic strategy for the prevention and treatment of Fas-associated liver injuries. PMID:27102561

  13. Acute kidney injury: current concepts and new insights

    Yavuzer Koza

    2016-01-01

    Abstract: Background: Acute kidney injury, which was previously named as acute renal failure, is a complex clinical disorder and continues to be associated with poor outcomes. It is frequently seen in hospitalized patients, especially in critically ill patients. The primary causes of acute kidney injury are divided into three categories: prerenal, intrinsic renal and postrenal. The definition and staging of acute kidney injury are mainly based on the risk, injury, failure, loss, end-stage kid...

  14. A SCUBA diver with acute kidney injury.

    Gleeson, Patrick James; Kelly, Yvelynne; Ni Sheaghdha, Eadaoin; Lappin, David

    2015-01-01

    An otherwise healthy young man was transferred to our hospital after a diving incident. He had made an uncontrolled ascent from 10 m. On arrival he appeared well. No hypotensive episodes occurred during the transfer. He denied having arthralgias, back pain, dyspnoea or neurological symptoms. Laboratory investigations revealed acutely elevated creatinine (170 µmol/L) and creatine kinase (909 U/L). Radiology was consistent with a focus of pulmonary barotrauma and intrinsic renal disease. Creatine kinase is a marker of arterial gas embolism (AGE). We determined that our patient suffered acute kidney injury as a result of gas embolisation to his renal vasculature from an area of pulmonary barotrauma. Creatinine fell the following day in response to aggressive intravenous fluids. This is the first reported case of acute kidney injury secondary to AGE. Biochemical studies should be part of the routine assessment of patients involved in diving incidents. PMID:25948841

  15. Alcoholic liver injury:Influence of gender and hormones

    Patricia; K; Eagon

    2010-01-01

    This article discusses several subjects pertinent to a consideration of the role of gender and hormones in alcoholic liver injury (ALI). Beginning with an overview of factors involved in the pathogenesis of ALI, we review changes in sex hormone metabolism resulting from alcohol ingestion, summarize research that points to estrogen as a cofactor in ALI, consider evidence that gut injury is linked to liver injury in the setting of alcohol, and briefly review the limited evidence regarding sex hormones and gut...

  16. Imatinib-induced fatal acute liver failure

    2007-01-01

    Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia (CML) in blast crisis, accelerated or chronic phase, and also for advanced gastrointestinal stromal tumors. Severe hepatic toxicity and three deaths from hepatic failure have been reported. We report the case of a 51-year-old woman who was admitted to our institution with severe acute hepatitis. She was diagnosed with CML and began treatment with imatinib mesylate at a dose of 400 mg/d.Five months after beginning treatment, she developed severe hepatitis associated with coagulopathy, and was admitted to our institution. She had been consuming acetaminophen 500-1000 mg/d after the onset of symptoms. She had a progressive increase in bilirubin level and a marked decrease of clotting factor Ⅴ. Five days after admission, grade Ⅱ encephalopathy developed and she was referred for liver transplantation. Her clinical condition progressively deteriorated, and 48 h after being referred for transplantation she suffered a cardiac arrest and died. This report adds concern about the possibility of imatinib-mesylate-induced hepatotoxicity and liver failure, particularly in the case of concomitant use with acetaminophen. Liver function tests should be carefully monitored during treatment and, with the appearance of any elevation of liver function tests, treatment should be discontinued.

  17. Acute Renal Failure in Liver Transplant Patients: Indian Study

    Naik, Pradeep; Premsagar, B.; Mallikarjuna, M.

    2013-01-01

    The acute renal failure is the frequent medical complication observed in liver transplant patients. The objective of this study was to determine the cause of acute renal failure in post liver transplant patients. A total of 70 patients who underwent (cadaveric 52, live 18) liver transplantation were categorized based on clinical presentation into two groups, namely hepatorenal failure (HRF, n = 29), and Hepatic failure (HF, n = 41). All the patients after the liver transplant had received tac...

  18. Herb-Induced Liver Injury in the Berlin Case-Control Surveillance Study.

    Douros, Antonios; Bronder, Elisabeth; Andersohn, Frank; Klimpel, Andreas; Kreutz, Reinhold; Garbe, Edeltraut; Bolbrinker, Juliane

    2016-01-01

    Herb-induced liver injury (HILI) has recently attracted attention due to increasing reports of hepatotoxicity associated with use of phytotherapeutics. Here, we present data on HILI from the Berlin Case-Control Surveillance Study. The study was initiated in 2000 to investigate the serious toxicity of drugs including herbal medicines. Potential cases of liver injury were ascertained in more than 180 Departments of all 51 Berlin hospitals from October 2002 to December 2011. Drug or herb intake was assessed through a standardized face-to-face interview. Drug or herbal aetiology was assessed based on the updated Council for International Organizations of Medical Sciences scale. In ten of all 198 cases of hepatotoxicity included in the study, herbal aetiology was assessed as probable (once ayurvedic herb) or possible (Valeriana five times, Mentha piperita once, Pelargonium sidoides once, Hypericum perforatum once, Eucalyptus globulus once). Mean age was 56.4 ± 9.7 years, and the predominant pattern of liver injury was hepatocellular. No cases of acute liver failure or death were observed. This case series corroborates known risks for ayurvedic herbs, supports the suspected association between Valeriana use and liver injury, and indicates a hepatotoxic potential for herbs such as Pelargonium sidoides, Hypericum perforatum or Mentha piperita that were rarely associated with liver injury before. However, given that possible causality does not prove clinical significance, further studies in this field are needed. PMID:26784183

  19. Herb-Induced Liver Injury in the Berlin Case-Control Surveillance Study

    Antonios Douros

    2016-01-01

    Full Text Available Herb-induced liver injury (HILI has recently attracted attention due to increasing reports of hepatotoxicity associated with use of phytotherapeutics. Here, we present data on HILI from the Berlin Case-Control Surveillance Study. The study was initiated in 2000 to investigate the serious toxicity of drugs including herbal medicines. Potential cases of liver injury were ascertained in more than 180 Departments of all 51 Berlin hospitals from October 2002 to December 2011. Drug or herb intake was assessed through a standardized face-to-face interview. Drug or herbal aetiology was assessed based on the updated Council for International Organizations of Medical Sciences scale. In ten of all 198 cases of hepatotoxicity included in the study, herbal aetiology was assessed as probable (once ayurvedic herb or possible (Valeriana five times, Mentha piperita once, Pelargonium sidoides once, Hypericum perforatum once, Eucalyptus globulus once. Mean age was 56.4 ± 9.7 years, and the predominant pattern of liver injury was hepatocellular. No cases of acute liver failure or death were observed. This case series corroborates known risks for ayurvedic herbs, supports the suspected association between Valeriana use and liver injury, and indicates a hepatotoxic potential for herbs such as Pelargonium sidoides, Hypericum perforatum or Mentha piperita that were rarely associated with liver injury before. However, given that possible causality does not prove clinical significance, further studies in this field are needed.

  20. Some biomarkers of acute kidney injury are increased in pre-renal acute injury

    Nejat, Maryam; Pickering, John W; Devarajan, Prasad; Edelstein, Charles L.; Walker, Robert J.; Endre, Zoltán H; Bonventre, Joseph Vincent

    2012-01-01

    Pre-renal acute kidney injury (AKI) is assumed to represent a physiological response to underperfusion. Its diagnosis is retrospective after a transient rise in plasma creatinine, usually associated with evidence of altered tubular transport, particularly that of sodium. In order to test whether pre-renal AKI is reversible because injury is less severe than that of sustained AKI, we measured urinary biomarkers of injury (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), \\(\\gamma\\...

  1. Dengue fever with acute liver failure

    Vinodh B; Bammigatti C; Kumar Ashok; Mittal V

    2005-01-01

    A virus belonging to the Flaviviridae group causes dengue haemorrhagic fever. Dengue presenting as acute liver failure is rare. Dengue is endemic in India. The last epidemic of dengue occurred in Delhi in 2003. During this epidemic, 2185 confirmed cases of dengue were reported. Dengue virus serotypes 2 and 3 were responsible for this epidemic. A 19-yr-old male presented to our hospital with the complaints of fever for 12 days, during this epidemic. He was diagnosed as having dengue shock synd...

  2. [Sequential changes in acute phase reactant proteins and complement activation in patients with acute head injuries].

    Ikeda, Y; Matsuura, H; Nakazawa, S

    1987-12-01

    The role of immunological mechanisms in head injury is not clearly defined. In this study we investigated the immunological function in patients with acute head injuries. Serum acute phase reactant proteins (APRP), complement activation and immunoglobulines as immunological parameters were studied. APRP are produced in the liver and increase in cancer patients as well as those with acute and chronic inflammations, trauma and autoimmune diseases. APRP are known to be one of the immunosuppressive factors in the serum. Forty patients with acute head injuries were studied. Thirty-four patients were male and six patients were female, ages ranged from 12 to 81 years. Serial blood samples were obtained during the first seven days of trauma. The Glasgow Coma Score (GCS) were recorded at the time of admission for all patients. Clinical outcome was assessed at the time of discharge according to the Glasgow Outcome Scale. The "good" group consisted of patients with good recovery or moderate disability. The "bad" group consisted of patients with severe disability, persistent vegetative state and death. The concentrations of immunoglobulines (IgG, IgM, IgA) were within normal range and humoral immunity was not affected. Complement activation at the time of admission was closely related to GCS (p less than 0.01), but the levels of C4, C3, and C3 activator except for these of CH50 were within normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2451531

  3. Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital.

    Mrzljak, Anna; Kosuta, Iva; Skrtic, Anita; Kanizaj, Tajana Filipec; Vrhovac, Radovan

    2013-01-01

    Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both agents were stopped and corticosteroids were initiated. Five months later the patient had fully recovered. Although in the literature the hepatotoxicity of noni juice remains speculative, sporadic but emerging cases of noni juice-associated liver injury address the need to clarify and investigate potential harmful effects associated with this supplement. PMID:23467452

  4. The innate immune response in ischemic acute kidney injury

    Jang, Hye Ryoun; Rabb, Hamid

    2008-01-01

    Kidney ischemia reperfusion injury is a major cause of morbidity in both allograft and native kidneys. Ischemia reperfusion-induced acute kidney injury is characterized by early, allo-antigen independent inflammation. Major components of the innate immune system are activated and participate in the pathogenesis of acute kidney injury, plus prime the allograft kidney for rejection. Soluble members of innate immunity implicated in acute kidney injury include the complement system, cytokines, an...

  5. Evaluation of liver function and electroacupuncture efficacy of animals with alcoholic liver injury by the novel imaging methods

    Zhang, Dong; Song, Xiao-jing; Li, Shun-yue; Wang, Shu-you; Chen, Bing-jun; Bai, Xiao-Dong; Tang, Li-mei

    2016-01-01

    Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect. The liver blood perfusion and indocyanine green (ICG) distribution were observe by LSPI and IVOI separately. After EA, the livers were collected to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), thromboxane A (TXA2), prostacyclin (PGI2) and endothelin (ET). The acquisitions of newly established LSPI of liver and ICG in vivo fluorescence imaging (ICG-IVFI), combining the results of other indexes showed: hepatic microcirculation perfusion (HMP) significantly reduced, ICG metabolism reduced, and ALT/AST increased in animal model with acute ALI. EA can reverse these changes. The use of LSPI of liver and ICG-IVFI, which was novel imaging methods for LF established in this study, could display the LF characteristics of ALI and the EA efficacy. PMID:27443832

  6. Metformin-Associated Acute Kidney Injury and Lactic Acidosis

    David Arroyo

    2011-01-01

    Full Text Available Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI. Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD has no influence on the severity or outcome.

  7. Hedgehog signaling and radiation induced liver injury: a delicate balance.

    Kabarriti, Rafi; Guha, Chandan

    2014-07-01

    Radiation-induced liver disease (RILD) is a major limitation of radiation therapy (RT) for the treatment of liver cancer. Emerging data indicate that hedgehog (Hh) signaling plays a central role in liver fibrosis and regeneration after liver injury. Here, we review the potential role of Hh signaling in RILD and propose the temporary use of Hh inhibition during liver RT to radiosensitize HCC tumor cells and inhibit their progression, while blocking the initiation of the radiation-induced fibrotic response in the surrounding normal liver. PMID:26202634

  8. Injury-induced changes of T1 in the liver

    The T1 of rat liver lengthens following any injury to any organ. A hypothesis explaining this holds that a substance (or substances), released from dead or injured cells, reaches liver, engaging it in healing. As a first step in testing this hypothesis, the authors injected rat liver homogenates into rates with previously measured liver T1. Homogenates are dead and injured cells, and their hypothesis predicts that liver T1 in homogenate-injected animals should lengthen. Lengthening of liver T1, measurable with their MR imager presently in clinical use, did result. Homogenates will be fractionated to determine if specific elements elicit the response

  9. Broad-spectrum matrix metalloproteinase inhibition curbs inflammation and liver injury but aggravates experimental liver fibrosis in mice.

    Vincent E de Meijer

    Full Text Available BACKGROUND: Liver fibrosis is characterized by excessive synthesis of extracellular matrix proteins, which prevails over their enzymatic degradation, primarily by matrix metalloproteinases (MMPs. The effect of pharmacological MMP inhibition on fibrogenesis, however, is largely unexplored. Inflammation is considered a prerequisite and important co-contributor to fibrosis and is, in part, mediated by tumor necrosis factor (TNF-alpha-converting enzyme (TACE. We hypothesized that treatment with a broad-spectrum MMP and TACE-inhibitor (Marimastat would ameliorate injury and inflammation, leading to decreased fibrogenesis during repeated hepatotoxin-induced liver injury. METHODOLOGY/PRINCIPAL FINDINGS: Liver fibrosis was induced in mice by repeated carbon tetrachloride (CCl4 administration, during which the mice received either Marimastat or vehicle twice daily. A single dose of CCl4 was administered to investigate acute liver injury in mice pretreated with Marimastat, mice deficient in Mmp9, or mice deficient in both TNF-alpha receptors. Liver injury was quantified by alanine aminotransferase (ALT levels and confirmed by histology. Hepatic collagen was determined as hydroxyproline, and expression of fibrogenesis and fibrolysis-related transcripts was determined by quantitative reverse-transcription polymerase chain reaction. Marimastat-treated animals demonstrated significantly attenuated liver injury and inflammation but a 25% increase in collagen deposition. Transcripts related to fibrogenesis were significantly less upregulated compared to vehicle-treated animals, while MMP expression and activity analysis revealed efficient pharmacologic MMP-inhibition and decreased fibrolysis following Marimastat treatment. Marimastat pre-treatment significantly attenuated liver injury following acute CCl4-administration, whereas Mmp9 deficient animals demonstrated no protection. Mice deficient in both TNF-alpha receptors exhibited an 80% reduction of serum ALT

  10. 外源性瘦素对重症急性胰腺炎肝损伤的机制研究%Protective effects of exogenous leptin on liver injury induced by severe acute pancreatitis

    颜琼; 黄元龙; 尹青; 杨丹; 邓明明

    2016-01-01

    目的:探讨外源性瘦素对重症急性胰腺炎(SAP)大鼠肝损伤的作用机制。方法将30只雄性SD大鼠随机分为假手术组、SAP组、瘦素干预组。采用逆行胰胆管注射3.5%牛黄胆酸钠制作SAP大鼠模型。瘦素干预组大鼠腹腔内注入瘦素20μg/kg。在术后12 h处死各组大鼠,取胰腺、肝脏组织进行HE染色、检测肝脏组织核因子‐κB(NF‐κB),采用细胞凋亡原位缺口末端标记法(TUNEL)测定肝脏组织的细胞凋亡指数,检测丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)及淀粉酶(AMY)水平。结果与假手术组比较,SAP组和瘦素干预组大鼠肝脏组织病理评分均明显增加(P<0.05);与SAP组比较,瘦素干预组大鼠肝脏组织病理评分降低(P<0.05);肝脏组织NF‐κB表达在SAP组和瘦素干预组较假手术组明显增加(P<0.01),与SAP组比较,瘦素干预组大鼠NF‐κB表达下降(P<0.05)。肝细胞凋亡指数SAP组、瘦素干预组大鼠均较假手术组明显增高(P<0.05),而瘦素干预组较SAP组降低(P<0.05)。SAP组和瘦素干预组大鼠 ALT、AST、AMY水平较假手术组显著增高(P<0.05),而瘦素干预组较SAP组降低(P<0.05)。结论外源性瘦素可能通过降低肝脏组织 NF‐κB的表达而降低肝细胞的凋亡指数起到保护SAP并发的肝损害作用。%Objective To investigate the effect and mechanism of exogenous leptin on liver injury in severe acute pancreatitis rat .Methods Thirty male SD rats were randomly divided into the sham operation group ,SAP group and leptin intervention group . The SAP rat models was established by retrograde injection of 3 .5% sodium taurocholate into the biliopancreatic duct .The leptin intervention group was intraperitoneally injected with leptin 20 μg/kg .The rats in each group were sacrificed at 12 h after model‐ing .The pancreas and

  11. A newly developed kit for the measurement of urinary liver-type fatty acid-binding protein as a biomarker for acute kidney injury in patients with critical care.

    Sato, Ryo; Suzuki, Yasushi; Takahashi, Gaku; Kojika, Masahiro; Inoue, Yoshihiro; Endo, Shigeatsu

    2015-03-01

    In recent years, it has been reported that the urinary level of Liver-type fatty acid-binding protein (L-FABP) serves as a useful biomarker for diagnosing acute kidney injury (AKI) or sepsis complicated by AKI. However, because the urinary level of L-FABP is currently measured by enzyme-linked immunosorbent assay (ELISA), several days may elapse before the results of the measurement become available. We have newly developed a simplified kit, the Dip-test, for measuring the urinary level of L-FABP. The Dip-test was measured at 80 measurement points (22 points in noninfectious disease, 13 points in SIRS, 20 points in infectious disease, and 25 points in sepsis) in 20 patients. The urinary L-FABP levels as determined by ELISA in relation to the results of the Dip-test were as follows: 10.10 ± 12.85 ng/ml in patients with a negative Dip-test ([-] group), 41.93 ± 50.51 ng/ml in patients with a ± test ([±] group), 70.36 ± 73.70 ng/ml in patients with a positive test ([+] group), 1048.96 ± 2117.68 ng/ml in patients with a 2 + test ([2+] group), and 23,571.55 ± 21,737.45 ng/ml in patients with a 3 + test ([3+] group). The following tendency was noted: the stronger the positive Dip-test reaction, the higher the urinary L-FABP level. Multigroup comparison revealed a significant differences in the urinary L-FABP levels between the Dip-test (-) group and each of the other groups. In this study, the usefulness of the Dip-test, our newly developed simplified kit for measuring the urinary L-FABP level, is suggested. PMID:25499195

  12. First aid for acute sports injuries.

    Bull, R C

    1987-09-01

    This article deals with management of acute sports injuries on the field or on the ice and in the dressing room or in the arena's first-aid room. Its most vital message is "Be prepared". A team approach and suitable ambulance and hospital back-up are mandatory. Individual management of a specific acute injury should be approached with a practice plan. Collars, splints, back board, doctor's bag, ambu bag, suture tray and emergency medications should be at hand. Care must be taken that no long-term harm befalls the player. The attending physician must be knowledgeable about preventive equipment and immediate institution of rehabilitation procedures, and must try to inform the coach or trainer and parent as to when the athlete can safely return to play. It is important that the athlete not return to play until he/she is 100% fit. PMID:21263977

  13. Sodium hypochlorite-induced acute kidney injury

    Brandon W Peck

    2014-01-01

    Full Text Available Sodium hypochlorite (bleach is commonly used as an irrigant during dental proce-dures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI. In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis.

  14. Severe liver injury induced by repeated use of hair dye

    HOU Feng-qin; LIN Xiao-hong; YU Yan-yan; WANG Tai-ling; WANG Gui-qiang

    2009-01-01

    @@ Asignificant number of drugs has been proven,or at least suggested,to cause hepatotoxicity.1-3 Liver injury due to herbal medicines,chemicals or natural toxins also occur from household,occupational,or environmental exposure.4,5 However,liver toxicity due to hair dyes now is rarely recognized.Only in 2003,Tokumoto et al6 reported a case of hair dye-induced hepatitis,which presented a comparatively mild liver lesion.Here we described a case had more severe liver injury.

  15. Dengue-associated acute kidney injury

    Oliveira, João Fernando Picollo; Burdmann, Emmanuel A

    2015-01-01

    Dengue is presently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. Acute kidney injury (AKI) is a serious and potentially lethal complication of this disease, and the actual incidence is unknown. In this review, we will assess the most relevant epidemiological and clinical data regarding dengue and the available evidence on the frequency, etiopathogenesis, outcomes and treatment of dengue-associated AKI.

  16. Mediators of Inflammation in Acute Kidney Injury

    Ali Akcay; Quocan Nguyen; Edelstein, Charles L.

    2010-01-01

    Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is now believed to play a major role in the pathopathophysiology of AKI. It is hypothesized that in ischemia, sepsis and nephrotoxic models that the initial insult results in morphological and/or functional changes in vascular endothelial cells and/or in tubular epithelium. Then, leukocytes including neutrophils, macrophages, natural killer cells, and lymphocytes infiltrate into the in...

  17. Determinants of postoperative acute kidney injury

    Abelha, Fernando José; Botelho, Miguela; Fernandes, Vera; Barros, Henrique

    2009-01-01

    Introduction Development of acute kidney injury (AKI) during the perioperative period is associated with increases in morbidity and mortality. Our aim was to evaluate the incidence and determinants of postoperative AKI after major noncardiac surgery in patients with previously normal renal function. Methods This retrospective cohort study was carried out in the multidisciplinary Post-Anaesthesia Care Unit (PACU) with five intensive care beds. The study population consisted of 1166 patients wi...

  18. Classification of acute subaxial cervical spine injury

    2012-01-01

    Abstract Study Design Literature review Objective The aim of this thesis is to compare the main classification systems available for classifying acute subaxial cervical spinal injury and compare their relative strengths and weaknesses, especially in their ability to guide treatment and predict prognosis. Methods A PICO question was formulated and used to select search terms. The search terms were used to search the online database Pubmed/Medline for English language revi...

  19. Liver injury associated with ketoconazole: review of the published evidence.

    Greenblatt, H Karl; Greenblatt, David J

    2014-12-01

    The azole antifungal agent ketoconazole has been available since 1981 for the treatment of fungal infections. In 2013, the American Food and Drug Administration and the European Medicines Agency issued warnings or prohibitions against the clinical use of oral ketoconazole due to the risk of liver injury which may lead to liver transplantation or death. From the available published evidence it is difficult to determine the actual incidence or prevalence of liver injury during clinical use of ketoconazole as an antifungal. Hepatic injury, when it occurs, is generally evident as asymptomatic and reversible abnormalities of liver function tests. However, serious liver injury has been reported. Alternatives to ketoconazole (such as itraconazole, fluconazole, voriconazole, and terbinafine) are available, but improved safety with respect to liver injury risk is not clearly established. We are not aware of published reports of significant ketoconazole-associated liver injury in volunteer study participants when ketoconazole has been used as a CYP3A inhibitor in the context of clinical research on drug metabolism. Possible alternatives to ketoconazole as prototype CYP3A inhibitors include ritonavir and potentially itraconazole, but not clarithromycin. PMID:25216238

  20. Extracorporeal support for patients with acute and acute on chronic liver failure.

    Aron, Jonathan; Agarwal, Banwari; Davenport, Andrew

    2016-04-01

    The number of patients developing liver failure; acute on chronic liver failure and acute liver failure continues to increase, along with the demand for donor livers for transplantation. As such there is a clinical need to develop effective extracorporeal devices to support patients with acute liver failure or acute-on-chronic liver failure to allow time for hepatocyte regeneration, and so avoiding the need for liver transplantation, or to bridge the patient to liver transplantation, and also potentially to provide symptomatic relief for patients with cirrhosis not suitable for transplantation. Currently devices can be divided into those designed to remove toxins, including plasma exchange, high permeability dialyzers and adsorption columns or membranes, coupled with replacement of plasma proteins; albumin dialysis systems; and bioartificial devices which may provide some of the biological functions of the liver. In the future we expect combinations of these devices in clinical practice, due to the developments in bioartificial scaffolds. PMID:26894968

  1. Interleukin-1 and acute brain injury

    Katie N Murray

    2015-02-01

    Full Text Available Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review.

  2. Injury potentials associated with severity of acute spinal cord injury in an experimental rat model

    Suying Pan; Guanghao Zhang; Xiaolin Huo; Jinzhu Bai; Tao Song

    2011-01-01

    To investigate characteristics of injury potentials after different degrees of spinal cord injury in rats, the present study established models of spinal cord contusion with severe, moderate, and mild degrees of injury. Injury potential was measured in vivo using a direct current voltage amplification system. Results revealed that in the first 4 hours after acute spinal cord injury, initial amplitude of injury potential was greatest after severe injury, followed by moderate and mild injuries. Amplitude of injury potential decreased gradually with injury time, and the recession curve was logarithmic. Under the same degree of injuries, amplitude of rostral injury potential was generally less than caudal injury potential. Results suggested that injury potential reflected injury severity, because large initial amplitude of injury potential during the early injury stage implied severe injury.

  3. Traditional Chinese Medicine Induced Liver Injury.

    Teschke, Rolf

    2014-06-01

    Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with particular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess the extent herbal TCM products exert rare hepatotoxicity. Analysis of reported cases revealed numerous specified herbal TCM products with potential hepatotoxicity. Among these were An Shu Ling, Bai Fang, Bai Xian Pi, Ban Tu Wan, Bo He, Bo Ye Qing Niu Dan, Bofu Tsu Sho San, Boh Gol Zhee, Cang Er Zi, Chai Hu, Chaso, Chi R Yun, Chuan Lian Zi, Ci Wu Jia, Da Chai Hu Tang, Da Huang, Du Huo, Gan Cao, Ge Gen, Ho Shou Wu, Hu Bohe You, Hu Zhang, Huang Qin, Huang Yao Zi, Hwang Geun Cho, Ji Gu Cao, Ji Ji, Ji Xue Cao, Jiguja, Jin Bu Huan, Jue Ming Zi, Kamishoyosan, Kudzu, Lei Gong Teng, Long Dan Xie Gan Tang, Lu Cha, Ma Huang, Mao Guo Tian Jie Cai, Onshido, Polygonum multiflorum, Qian Li Guang, Ren Shen, Sairei To, Shan Chi, Shen Min, Shi Can, Shi Liu Pi, Shou Wu Pian, Tian Hua Fen, White flood, Wu Bei Zi, Xi Shu, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao, and various unclassified Chinese herbal mixtures. Causality was firmly established for a number of herbal TCM products by a positive reexposure test result, the liver specific scale of CIOMS (Council for International Organizations of Medical Sciences), or both. Otherwise, the quality of case data was mixed, especially regarding analysis of the herb ingredients because of adulteration with synthetic drugs, contamination with heavy metals, and misidentification. In addition, non-herbal TCM elements derived from Agaricus blazei, Agkistrodon, Antelope, Bombyx, Carp, Fish gallbladder, Phellinus, Scolopendra, Scorpio, and Zaocys are also known or potential hepatotoxins. For some patients, the clinical course was severe, with risks for acute liver failure, liver transplantation requirement, and lethality. In conclusion, the use of few herbal TCM products may rarely be associated with hepatotoxicity in some

  4. Liver injury caused by drugs: an update.

    Stirnimann, Guido; Kessebohm, Kerstin; Lauterburg, Bernhard

    2010-01-01

    Although severe idiosyncratic drug-induced liver injury (DILI) is a rare event, it has a large impact on the fate of affected patients and the incriminated drug. Hepatic metabolism of drugs, which occurs in the generation of chemically reactive metabolites in critical amounts, seems to underlie most instances of DILI. Genetic polymorphisms in activating and detoxifying enzymes determine, in part, the extent of cellular stress. A cascade of events, where the pathogenetic relevance of single steps is likely to vary from drug to drug, leads to the disturbance of cellular homeostasis, to mitochondrial dysfunction, to the activation of cell death promoting pathways and the release of drug-modified macromolecules and/or danger signals that initiate an innate and/or adaptive immune response. The patient's response to the initial drug-induced cellular dysfunction determines whether adaptation to the drug-induced cellular stress or DILI in one of its many forms of clinical presentation occurs. Although risk factors for developing DILI have been identified and many pathogenetic mechanisms have been elucidated in model systems, idiosyncratic drug reactions remain unpredictable. PMID:20927685

  5. LATE ACUTE REJECTION IN LIVER TRANSPLANT: A SYSTEMATIC REVIEW

    Nacif, Lucas Souto; Pinheiro, Rafael Soares; PÉCORA, Rafael Antônio de Arruda; Ducatti, Liliana; ROCHA-SANTOS, Vinicius; Andraus, Wellington; D'ALBUQUERQUE, Luiz Carneiro

    2015-01-01

    Introduction: Late acute rejection leads to worse patient and graft survival after liver transplantation. Aim: To analyze the reported results published in recent years by leading transplant centers in evaluating late acute rejection and update the clinical manifestations, diagnosis and treatment of liver transplantation. Method: Systematic literature review through Medline-PubMed database with headings related to late acute rejection in articles published until November 2013 was done. Were a...

  6. Steroid use in Acute Liver Failure

    Karkhanis, Jamuna; Verna, Elizabeth C.; Chang, Matthew S.; Stravitz, R. Todd; Schilsky, Michael; Lee, William M; Brown, Robert S

    2014-01-01

    Background/Aims Drug-induced and indeterminate Acute Liver Failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced or indeterminate ALF, and whether this benefit varies according to the severity of illness. Methods We conducted a retrospective analysis of autoimmune, indeterminate and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). Results 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% vs. 66%, p=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of MELD (MELD > 40, survival 30% vs. 57%, p=0.03). In multivariable analysis controlling for steroid use and diagnosis, age (OR 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07) and pHsteroid use was associated with a marginal benefit in SS overall (35% v. 23%, p=0.047), this benefit did not persistent in multivariable analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and ALT (1.02) were the only significant predictors of SS. Conclusions Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores. PMID:23929808

  7. Carbon tetrachloride-induced liver injury in the rabbit.

    Bernacchi, A. S.; de Castro, C. R.; de Ferreyra, E. C.; Villarruel, M. C.; Fernández, G.; de Fenos, O. M.; Castro, J. A.

    1983-01-01

    CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h. Nevertheless, the intensity of this process is not equivalent to that occurring in rat liver microsomes, since the arachidonic acid content of rabbit liver microsomal lipids does not decrease at either 6 or 24 h after CCl4 administration. Rabbit liver is able to activate CCl4 to reactive metabolites that bind covalently to lipids. Relevance of covalent binding of CCl4 reactive metabolites and CCl4-promoted lipid peroxidation to CCl4-induced rabbit liver injury is analysed. Images Fig. 1 Fig. 2 PMID:6309207

  8. Acute injury of the ankle joint

    The diagnosis of lateral collateral ankle ligament trauma is based on patient history, clinical examination, and clinical stress tests. If the clinical stress test is positive, stress radiography could be performed. There is no consensus about the usefulness of stress radiography in acute ankle sprain, particularly about the cut-off talar tilt angle beyond which a two-ligament rupture would be certain, ranging from 5 to 30 . Today MRI is not used for this indication, although it allows, with controlled positioning of the foot and with defined sections, visualization of injured lateral collateral ankle ligaments. In ankle injuries, plain radiographs form the established basis of diagnostic imaging and can provide definitive answers in most cases. CT is used in complex fractures for complete visualization. MRI is the method of choice for several diagnostic problem cases, including occult fractures and post-traumatic avascular necrosis. In tendon injuries, MRI is important if ultrasound is not diagnostic. Generally, for the evaluation of acute ankle injuries, MRI is the most important second-step procedure when radiographs are nondiagnostic. (orig.)

  9. Immune mechanisms in acetaminophen-induced acute liver failure.

    Krenkel, Oliver; Mossanen, Jana C; Tacke, Frank

    2014-12-01

    An overdose of acetaminophen (N-acetyl-p-aminophenol, APAP), also termed paracetamol, can cause severe liver damage, ultimately leading to acute liver failure (ALF) with the need of liver transplantation. APAP is rapidly taken up from the intestine and metabolized in hepatocytes. A small fraction of the metabolized APAP forms cytotoxic mitochondrial protein adducts, leading to hepatocyte necrosis. The course of disease is not only critically influenced by dose of APAP and the initial hepatocyte damage, but also by the inflammatory response following acetaminophen-induced liver injury (AILI). As revealed by mouse models of AILI and corresponding translational studies in ALF patients, necrotic hepatocytes release danger-associated-molecular patterns (DAMPs), which are recognized by resident hepatic macrophages, Kupffer cell (KC), and neutrophils, leading to the activation of these cells. Activated hepatic macrophages release various proinflammatory cytokines, such as TNF-α or IL-1β, as well as chemokines (e.g., CCL2) thereby further enhancing inflammation and increasing the influx of immune cells, like bone-marrow derived monocytes and neutrophils. Monocytes are mainly recruited via their receptor CCR2 and aggravate inflammation. Infiltrating monocytes, however, can mature into monocyte-derived macrophages (MoMF), which are, in cooperation with neutrophils, also involved in the resolution of inflammation. Besides macrophages and neutrophils, distinct lymphocyte populations, especially γδ T cells, are also linked to the inflammatory response following an APAP overdose. Natural killer (NK), natural killer T (NKT) and T cells possibly further perpetuate inflammation in AILI. Understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression is essential to identify novel therapeutic targets for human disease. PMID:25568858

  10. The Anatomic Pattern of Injuries in Acute Inversion Ankle Sprains

    Khor, Yuet Peng; Tan, Ken Jin

    2013-01-01

    Background: There are little data on the incidence and patterns of injuries seen on magnetic resonance imaging (MRI) in acute inversion ankle sprains. This study may help in the understanding of the pathomechanics, natural history, and outcomes of this common injury. Study Design: Case series; Level of evidence, 4. Methods: From June 2011 to June 2013, a total of 64 consecutive patients had MRI of the ankle performed for acute inversion injury to the ankle. All injuries/pathologies reported w...