A new approach to facilitate diagnosis of nonalcoholic fatty liver disease through a galactose single point method in rats with fatty liver

Lee, Jr Ting; Pao, Li-Heng; Lee, Meei Shyuan; Liao, Jiunn‐Wang; Shih, Chi Min; Hsiong, Cheng Huei; Yin, Fon Yi; Shih, Tiffany Ting-Fang; Hu, Oliver Yoa Pu

doi:10.1016/j.dld.2012.08.019

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…The GSP method has been successfully used to predict prognoses and is correlated with the severity of liver disease, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and nonalcoholic fatty liver disease (19)(20)(21)(22)(23). The FDA has recommended the GSP method in its industry pharmacokinetics guidelines for patients with impaired hepatic function.…”

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confidence: 99%

A Novel Mechanism Underlies the Hepatotoxicity of Pyrazinamide

Shih

Pai

Yang

et al. 2013

Antimicrob Agents Chemother

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cRelatively little is known about the hepatotoxicity of pyrazinamide (PZA). PZA requires activation by amidase to form pyrazinoic acid (PA). Xanthine oxidase then hydroxylates PA to form 5-hydroxypyrazinoic acid (5-OH-PA). PZA can also be directly oxidized to form 5-OH-PZA. Before this study, it was unclear which metabolic pathway or PZA metabolites led to hepatotoxicity. This study determines whether PZA metabolites are responsible for PZA-induced hepatotoxicity. PZA metabolites were identified and cytotoxicity in HepG2 cells was assessed. Potential PZA and PA hepatotoxicity was then tested in rats. Urine specimens were collected from 153 tuberculosis (TB) patients, and the results were evaluated to confirm whether a correlation existed between PZA metabolite concentrations and hepatotoxicity. This led to the hypothesis that coadministration of amidase inhibitor (bis-p-nitrophenyl phosphate [BNPP]) decreases or prevents PZA-and PZA metabolite-induced hepatotoxicity in rats. PA and 5-OH-PA are more toxic than PZA. Electron microscopy showed that PZA and PA treatment of rats significantly increases aspartate transaminase (AST) and alanine aminotransferase (ALT) activity and galactose single-point (GSP) levels (P < 0.005). PA and 5-OH-PA levels are also significantly correlated with hepatotoxicity in the urine of TB patients (P < 0.005). Amidase inhibitor, BNPP, decreases PZA-induced, but not PA-induced, hepatotoxicity. This is the first report of a cell line, animal, and clinical trial confirming that the metabolite 5-OH-PA is responsible for PZA-induced hepatotoxicity.

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confidence: 99%

A Novel Mechanism Underlies the Hepatotoxicity of Pyrazinamide

Shih

Pai

Yang

et al. 2013

Antimicrob Agents Chemother

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“…These target nodes were identified as key genes and might be potential therapeutic targets for the treatment of NAFLD by ZWD. Alkaline phosphatase, ALT, AST, ALB and total serum protein were significantly correlated with the severity of NAFLD [12] . Besides, there were significant differences in the ALB-binding function between healthy subjects and different severity groups of NAFLD [13] .…”

Section: Table 1: the Nucleotide Sequences Of The Primer Pairs Used F...mentioning

confidence: 91%

Study on the Mechanism of Zhenwu Decoction in Decreasing the Fats in Non-Alcoholic Fatty Liver Disease Using System Pharmacology and Cytological Validation Test

Zhang¹,

Fang²,

Tang³

et al. 2022

IJPS

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Zhang et al.: Mechanism of Zhenwu Decoction in Decreasing the Fats in Non-alcoholic Fatty Liver Disease Purpose of this study was to screen the active compounds of Zhenwu decoction and their gene targets in the treatment of non-alcoholic fatty liver disease by network pharmacology and cytological validation test. The candidate compounds and related targets of Zhenwu decoction were obtained from traditional Chinese medicine system pharmacology database and PharmMapper. The non-alcoholic fatty liver disease-related genes were obtained from online Mendelian inheritance in man, GeneCards and DisGeNET databases. Molecular docking was carried out to simulate the binding affinities between potential core compounds and key target genes, and the chemical constituents of Zhenwu decoction were analyzed and identified by Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry technology.Therapeutic effect and mechanism of Zhenwu decoction on non-alcoholic fatty liver disease were validated using in vitro analysis. The protein-protein interaction network analysis identified the albumin, protein kinase B1, epidermal growth factor receptor, caspase 3 and peroxisome proliferator activated receptor gamma as the key target genes. Gene ontology annotation analysis showed that the Zhenwu decoctionnon-alcoholic fatty liver disease target genes were mainly involved in the response to steroid hormone and lipid catabolic process. The results of the Kyoto encyclopedia of genes and genomes pathway enrichment analysis were mainly related to the Forkhead box O signaling pathway and phosphatidylinositol 3-kinaseprotein kinase B signaling pathway. Paeoniflorgenone had the highest binding affinities for albumin, protein kinase B1, epidermal growth factor receptor, caspase 3 and peroxisome proliferator activated receptor gamma. The in vitro experiment showed that 19.5 mg/ml (p≤0.05) and 39 mg/ml (p≤0.01) of Zhenwu decoction could reduce lipid accumulation. Real-time quantitative polymerase chain reaction analyses revealed that Zhenwu decoction induced down-regulation of epidermal growth factor receptor messenger ribonucleic acid levels and up-regulation of heat shock protein 90 alpha family class a member 1, mitogen-activated protein kinase 1 and phosphatidylinositol 3-kinase messenger ribonucleic acid levels.

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“…Data are reported as g TG mg Ϫ1 (wet weight) liver tissue. To evaluate liver damage, plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) enzyme levels were measured, which are indicators of hepatocyte damage/leakage and cholangiocyte stress, respectively (30,31). Blood was collected into heparinized tubes at necropsy, and ALT and ALP levels were quantified by using a Mammalian Liver Profile rotor in a VetScan VS2 analyzer (Abaxis, Union City, CA).…”

Section: Methodsmentioning

confidence: 99%

In Vivo Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

Krumbeck

Maldonado-Gómez

Martínez

et al. 2015

Appl Environ Microbiol

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One strategy for enhancing the establishment of probiotic bacteria in the human intestinal tract is via the parallel administration of a prebiotic, which is referred to as a synbiotic. Here we present a novel method that allows a rational selection of putative probiotic strains to be used in synbiotic applications: in vivo selection (IVS). This method consists of isolating candidate probiotic strains from fecal samples following enrichment with the respective prebiotic. To test the potential of IVS, we isolated bifidobacteria from human subjects who consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A retrospective analysis of the fecal microbiota of one subject revealed an 8-fold enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS administration. The functionality of GOS to support the establishment of IVS-1 in the gastrointestinal tract was then evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that the addition of GOS increased B. adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to outcompete the resident Bifidobacterium population when provided with GOS. In conclusion, this study demonstrated that IVS can be used to successfully formulate a synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract.T he mechanistic role of the gastrointestinal (GI) microbiota and its metabolites in maintaining human health has been well demonstrated (1-3). Gut microbes provide several important benefits for their host, including provision of nutrients, development and maturation of the immune system, and protection against pathogens via colonization resistance (4). However, the gut microbiota may also contribute to obesity, inflammatory and autoimmune diseases, and other chronic disease states (5-7). Such diseases are often associated with compositional alterations in the fecal microbiota, a condition referred to as "dysbiosis" (8). Given that the presence of specific types of bacteria and their relative abundance within the gut are considered to affect host health, there is much interest in devising strategies that modulate gut microbiota composition and potentially redress disease-related dysbiotic patterns (9).Dietary approaches currently available to modulate the gut microbiota include prebiotics (10-12), fermentable fibers (13, 14), probiotics (or live biotherapeutics) (15), and synbiotics, which are a combination of a probiotic and a prebiotic (11, 16). According to Kolida and Gibson (16), synbiotics can be either complementary or synergistic. Complementary synbiotics consist of a probiotic and a prebiotic selected to independently confer benefits to the host. In contrast, sy...

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A new approach to facilitate diagnosis of nonalcoholic fatty liver disease through a galactose single point method in rats with fatty liver

Cited by 4 publications

References 42 publications

A Novel Mechanism Underlies the Hepatotoxicity of Pyrazinamide

A Novel Mechanism Underlies the Hepatotoxicity of Pyrazinamide

Study on the Mechanism of Zhenwu Decoction in Decreasing the Fats in Non-Alcoholic Fatty Liver Disease Using System Pharmacology and Cytological Validation Test

In Vivo Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

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