Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure

Wang, Likun; Wang, Lu-Wen; Li, Xun; Han, Xiao-Qun; Gong, Zuojiong

doi:10.1016/s1499-3872(13)60029-6

Cited by 33 publications

(17 citation statements)

References 31 publications

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“…In the acute deterioration phase, d -gal/LPS was administered to exacerbate the pathophysiological processes of ACLF. LPS, a critical component of the cell membrane of Gram-negative bacteria, could activate kupffer cells via toll-like receptor 4 (TLR4)-mediated mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF- κ B) signal pathways, and stimulate the production and release of inflammatory factors including TNF- α which will induce apoptosis and necrosis of hepatocytes 15 . d -Gal is an amino sugar that is selectively metabolized by hepatocytes, and which induces liver damage by depletion of the uridine triphosphate pool and thereby inhibits protein synthesis.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a new acute-on-chronic liver failure model

Miao

Sun

et al. 2017

Acta Pharmaceutica Sinica B

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To establish an animal model of acute-on-chronic liver failure (ACLF) that would replicate the pathological process of ACLF in humans, rats were administered porcine serum (PS) for 11 weeks. Liver fibrosis was determined by pathological and biochemical assessments. The animals then were injected with d-galactosamine (d-gal) and lipopolysaccharide (LPS). The survival times of animals with cirrhosis and ACLF were determined over 48 h. Other animals were killed at 0, 4, 8 and 12 h after administration of d-gal/LPS. Liver injury was assessed by histopathological analysis and biochemical indices, and apoptosis was detected by Western blot and TUNEL analysis. After PS administration for 11 weeks the serum levels of hyaluronic acid and N-procollagen type III peptide increased significantly, and serious fibrosis and cirrhosis was observed at weeks 10 and 11. Cirrhotic rats were injected with d-gal/LPS to induced ACLF; the rate of mortality over 48 h was 80%. ALT and AST levels increased markedly at 4 h, but decreased significantly at 8 and 12 h post-treatment. The total bilirubin, direct bilirubin, and total bile acids levels increased markedly at 8 and 12 h. Clotting times, TNF-α and IL-6 levels increased significantly, except for 12 h post-treatment. Apoptosis, inflammation and necrosis were elevated as determined by hematoxylin-eosin staining and TUNEL assays. BCL-2 levels decreased significantly, While BAX levels increased significantly. Cytochrome c expression peaked at 8 h post-d-gal/LPS treatment. In conclusion, an ACLF model induced by PS and d-gal/LPS was established and the underlying mechanisms of ACLF development were explored.

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Section: Discussionmentioning

confidence: 99%

Establishment of a new acute-on-chronic liver failure model

Miao

Sun

et al. 2017

Acta Pharmaceutica Sinica B

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“…It is reproducibly established that liver damage and failure are the direct cause of death of the animals, it has an appropriate therapeutic window, it can be used in large experimental animals, and it is safe for scientists carrying out the experiments. Although the partial reversibility may be a limitation, the results of some studies suggested that certain substances can slow down the development of GAL-induced ALF [ 23 , 24 ]. As noted previously, the model of ALF used in the present study is employed less frequently than other models, and its value is probably underappreciated [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

D-Galactosamine Intoxication in Experimental Animals: Is it Only an Experimental Model of Acute Liver Failure?

et al. 2015

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BackgroundShort-term administration of Galactosamine to experimental animals causes liver damage and acute liver failure (ALF), as well as acute renal failure in some cases. The aim of our study was to describe kidney disorders that developed in the course of galactosamine-induced liver failure.Material/MethodsSprague-Dawley rats were randomly divided into 2 groups: a study group administered galactosamine intraperitoneally and a control group administered saline.ResultsAll the animals in the study group developed liver damage and failure within 48 h, with significant increase of alanine (p<0.001), aspartate aminotransferases (p<0.0001), bilirubin (p<0.004), and ammonia (p<0.005) and decrease of albumin (p<0.001) concentrations. Acute renal failure was observed in all test animals, with a significant increase in creatinine (p<0.001) and urea (p<0.001) concentrations and a decrease in creatinine clearance (p<0.0012). Moreover, osmotic clearance (p<0.001), daily natriuresis (p<0.003), and fractional sodium excretion (p<0.016) decreased significantly in this group of animals. The ratio of urine osmolality to serum osmolality did not change. Histopathology of the liver revealed massive necrosis of hepatocytes, whereas renal histopathology showed no changes.ConclusionsAcute renal failure that developed in the course of galactosamine-induced ALF was of a functional nature, with the kidneys retaining the ability to concentrate urine and retain sodium, and there were no renal changes in the histopathological examination. It seems that the experimental model of ALF induced by galactosamine can be viewed as a model of hepatorenal syndrome that occurs in the course of acute damage and liver failure.

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“…Increased intestinal permeability due to damaged intestinal mucosal barrier increases hepatic endotoxin influx, which in turn activates Kupffer cells and the production of pro-inflammatory cytokines, arachidonic acid metabolites and ROS in the liver [85]. In experimental models, intestine-derived endotoxin or co-administration of LPS enhances liver injury induced by chemicals [86,87], while decreased intestinal permeability reduced liver injury [88]. Likely, a disrupted mucosal barrier induced by drugs (e.g.…”

Section: Dominant Induction Of Necrosis Vs Apoptosis Acetaminophen mentioning

confidence: 99%

Drug-induced liver injury: Interactions between drug properties and host factors

Chen

Suzuki

Borlak

et al. 2015

Journal of Hepatology

319

282

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Idiosyncratic drug-induced liver injury (DILI) is a common cause for drug withdrawal from the market and although infrequent, DILI can result in serious clinical outcomes including acute liver failure and the need for liver transplantation. Eliminating the iatrogenic "harm" caused by a therapeutic intent is a priority in patient care. However, identifying culprit drugs and individuals at risk for DILI remains challenging. Apart from genetic factors predisposing individuals at risk, the role of the drugs' physicochemical and toxicological properties and their interactions with host and environmental factors need to be considered. The influence of these factors on mechanisms involved in DILI is multi-layered. In this review, we summarize current knowledge on 1) drug properties associated with hepatotoxicity, 2) host factors considered to modify an individuals' risk for DILI and clinical phenotypes, and 3) drug-host interactions. We aim at clarifying knowledge gaps needed to be filled in as to improve risk stratification in patient care. We therefore broadly discuss relevant areas of future research. Emerging insight will stimulate new investigational approaches to facilitate the discovery of clinical DILI risk modifiers in the context of disease complexity and associated interactions with drug properties, and hence will be able to move towards safety personalized medicine.

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Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure

Cited by 33 publications

References 31 publications

Establishment of a new acute-on-chronic liver failure model

Establishment of a new acute-on-chronic liver failure model

D-Galactosamine Intoxication in Experimental Animals: Is it Only an Experimental Model of Acute Liver Failure?

Drug-induced liver injury: Interactions between drug properties and host factors

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