Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

Constantinou, Maria; Theocharis, Stamatios; Mikros, Emmanuel

doi:10.1016/j.taap.2006.10.007

Cited by 67 publications

(57 citation statements)

References 42 publications

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“…Biochemical alterations are attributed to the elevated rate of glycogenolysis and glycolysis and the observed increase in the lipid levels is attributed to the drug-induced lipid accumulation. NMR spectra from liver extracts and serum samples obtained at different time points after prolonged TAA administration (corresponding to early, late fibrosis and cirrhosis states) suggest increase rate of glycogenolysis and glycolysis in chronic liver injury, being in agreement with the findings noted in acute liver injury caused by the same agent (Constantinou et al, 2007). The variations of amino acids levels in serum are proportional to the degree of liver damage, since the protein synthesis is disturbed and necrosis causes protein degradation.…”

Section: Discussionsupporting

confidence: 82%

“…Recently, metabonomic approaches have been established in animal models of acute (Coen et al, 2003;Wang et al, 2003;Bollard et al, 2005;Waters et al, 2005) and chronic (Constantinou et al, 2007) liver injury. Acetaminophen (also known as 396 paracetamol and N-acetyl-p-aminophenol, APAP) is a commonly used pharmaceutical analgesic and antipyretic agent.…”

Section: Introductionmentioning

confidence: 99%

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Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum

Zira

Mikros

Giannioti

et al. 2009

J of Applied Toxicology

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The metabonomic approach has been widely used in toxicology to investigate mechanisms of toxicity. In the present study alterations in the metabolic profiles, monitored by (1)H-NMR spectroscopy, on serum samples in acetaminophen (APAP)-induced liver injury in rabbits were examined. Furthermore, the effect of the established antidote N-acetylcysteine (NAC) and the proposed antidotes silybinin (SIL), cimetidine (CIM) and SIL/CIM was also investigated. A single dose of APAP (2 g kg(-1) b.w., i.g.) was administered to rabbits and APAP combined with the antidotes SIL, CIM and NAC. Animals were sacrificed at 24 h post-APAP treatment. Healthy untreated animals served as controls. (1)H-NMR spectra of serum samples were acquired and underwent principal component analysis (PCA). Acute liver injury was verified by histopathological examination and the alterations of serum biochemical enzymes AST and ALT. (1)H-NMR spectroscopy revealed variations in the serum metabolic profile of APAP-intoxicated rabbits compared with controls. Co-administration of APAP with NAC, CIM and SIL + CIM seems to ameliorate the metabolic profile of animals compared with simply APAP-treated ones. In this study, the model of APAPinduced liver injury was successfully described using the (1)H-NMR based metabonomic approach in serum. Furthermore, the use of antidotes that reduced the toxic insult was also recorded using this technique. The combination of NMR spectroscopy and PCA is a rapid methodology, capable of detecting alterations in the metabolic profile, and produces adequate models that could be used for the characterization of unknown samples, both experimental and clinical, reinforcing its future use in clinical settings.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum

Zira

Mikros

Giannioti

et al. 2009

J of Applied Toxicology

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“…Aberrant amino acid biosynthesis may be a hallmark with an increase in the severity of cirrhosis as well as alterations 6 Hepat Mon. 2017; 17(3):e44431.…”

Section: Discussionmentioning

confidence: 99%

“…Studying cirrhosis is imperative because of (i) its high mortality rate worldwide, resulting in 1.2 million deaths in 2013 (3) and a 10-year mortality rate of 34% to 66%, depending on the cirrhosis (4); and (ii) approximately 70% to 90% of patients with hepatocellular carcinoma (HCC) have an established background of chronic liver disease and cirrhosis (5). Data from studies have suggested a paradigm for the pathogenesis of cirrhosis involving alterations of oxidative stress that provoke the inflammatory and apoptotic reactions in the generation of cirrhosis (6). Unfortunately, these biomarkers are not liver specific and still require extensive validation.…”

Section: Introductionmentioning

confidence: 99%

Serum Metabolic Profiling of Advanced Cirrhosis Based on HCV

et al. 2017

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Background: Cirrhosis is recognized by a reduction in hepatocyte proliferation with an increase in fibrous tissue, which may ultimately lead to the development of cancerous nodules. Liver biopsy has remained the gold standard for confirming liver fibrosis stages, but there are not any nonreversible and specific therapeutic targets in advanced cirrhosis. In the present study, we used the NMR method to find potential therapeutic markers in serum of HCV -cirrhotic patients with advanced stage.Methods: A metabolic profiling study was conducted using 2 groups: decompensated HCV-cirrhosis patients (n = 21) and healthy controls (n = 18). 1H nuclear magnetic resonance (NMR) approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by the multivariate principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Moreover, metabolic pathways were determined using MetaboAnalyst 3.0.Results: Specifically, 16 metabolites showed alteration between the 2 groups. Compared with healthy controls, a number of metabolites showed increased concentration in serum of decompensated HCV-cirrhosis such as succinic acid, isovaleraldehyde, citrulline, propanal and cinnamaldehyde, while several others were observed in decreased levels in the decompensated HCV-cirrhosis such as valine, glutamine, trimethylamine, lactate, proline, aspartate, lipid, VLDL, isoleucine, fucose, and glutamate. Aminoacyl-tRNA biosynthesis, alanine, aspartate, glutamate metabolism and arginine, and proline metabolism are the most significant pathways associated with advanced HCV-cirrhosis. Conclusions:Metabolomic profiling through NMR can identify the metabolic disturbances in advanced HCV-cirrhosis. Aberrant amino acid biosynthesis may be the hallmark with increasing severity of cirrhosis as well as alterations in energetic metabolism.

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“…TAA-induced hepatic diseases in rat is a good model for determining the anti-inflammatory potential of natural products as it perfectly mimics human chronic hepatic diseases, including viral hepatitis [12] and fibrosis [13]. Cytochrome P2E1 and flavin adenine dinucleotide monooxygenases catalyse the conversion of TAA to TAA-Soxide and TAA-S-dioxide, both of which may be involved in TAA-associated hepatic injury caused by ROS production and lipid peroxidation [14,15].…”

mentioning

confidence: 99%

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Ali

Darwish

Ismail

2015

Basic Clin Pharma Tox

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Chronic hepatitis is recognized as a worldwide health problem that gradually progresses towards cirrhosis and hepatocellular carcinoma. Despite the large number of experiments using animal models for allergic hepatitis, it is still difficult to produce a picture of chronic hepatitis. Therefore, this study was conducted to introduce an animal model approximating to the mechanism of chronicity in human hepatitis. The study also aimed to examine the hepatoprotective effects of curcumin, silybin phytosome â and a-R-lipoic acid against thioacetamide (TAA)-induced chronic hepatitis in rat model. TAA was administered intraperitoneally at a dose of 200 mg/kg three times weekly for 4 weeks. At the end of this period, a group of rats was killed to assess the development of chronic hepatitis in comparison with their respective control group. TAA administration was then discontinued, and the remaining animals were subsequently allocated into four groups. Group 1 was left untreated, whereas groups 2-4 were allowed to receive daily oral doses of curcumin, silybin phytosome â or a-R-lipoic acid, respectively, for 7 weeks. Increases in hepatic levels of malondialdehyde associated with TAA administration were inhibited in groups receiving supplements. Furthermore, glutathione depletion, collagen deposition, macrophage activation and nuclear factor jappa-B expression as well as tumour necrosis factor-a and interleukin-6 levels were significantly decreased in response to supplements administration. Serological analysis of liver function and liver histopathological examination reinforced the results. The above evidence collectively indicates that the antioxidant and anti-inflammatory activities of curcumin, silybin phytosome â and a-R-lipoic acid may confer therapeutic efficacy against chronic hepatitis.

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Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

Cited by 67 publications

References 42 publications

Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum

Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum

Serum Metabolic Profiling of Advanced Cirrhosis Based on HCV

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

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Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats

Cited by 67 publications

References 42 publications

Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum

Acute liver acetaminophen toxicity in rabbits and the use of antidotes: a metabonomic approach in serum

Serum Metabolic Profiling of Advanced Cirrhosis Based on HCV

Curcumin, Silybin Phytosome® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Contact Info

Product

Resources

About

Curcumin, Silybin Phytosome^® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production