Integrated systems toxicology approaches identified the possible involvement of ABC transporters pathway in erythromycin estolate-induced liver injury in rat

Lu, Xiaoyan; Tian, Yu; Lian, Xueping; Jin, Yachao; Jin, Tingting; Zhao, Qinqin; Hu, Bin; Shen, Xiu; Fan, Xiaohui

doi:10.1016/j.fct.2013.12.050

Cited by 15 publications

(7 citation statements)

References 57 publications

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“…We did identify a two-step event occurring with acetaminophen, the first linked to calcium flux and the second to oxidative stress and downregulation of mitochondrial activity, as already suggested (Bajt et al, 2004 andJaeschke et al, 2012). Using HCS, we also demonstrated, as already suggested by many studies, that retinoic acid (Ribeiro et al, 2013;Tan et al, 2008), amodiaquine (Tafazoli and O'Brien, 2009), cyclophosphamide (Kumari and Setty, 2012;Tripathi and Jena, 2010), diethylstilbestrol (Kipp and Ramirez, 2001;Li et al, 2011) anderythromycin (Anandatheerthavarada et al, 1999;Lu et al, 2014) induced oxidative stress and mitochondrial dysfunction. Interestingly, coupling information from HCS and xCELLigence allowed us to conclude that amodiaquine first acts on mitochondria before inducing ROS production.…”

Section: Nevertheless Kinetics Of Effects and Cell Index Curves Coulsupporting

confidence: 64%

High-content screening imaging and real-time cellular impedance monitoring for the assessment of chemical’s bio-activation with regards hepatotoxicity

Peyre

Sousa

Barcellini-Couget

et al. 2015

Toxicology in Vitro

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Section: Nevertheless Kinetics Of Effects and Cell Index Curves Coulsupporting

confidence: 64%

High-content screening imaging and real-time cellular impedance monitoring for the assessment of chemical’s bio-activation with regards hepatotoxicity

Peyre

Sousa

Barcellini-Couget

et al. 2015

Toxicology in Vitro

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“…Du X. W. also found that alanine, aspartate and glutamate metabolism was closely related to liver injury (Du et al, 2013 ). Lu X. Y. reported the close relationship of ABC transporters with liver injury (Lu et al, 2014 ).…”

Section: Resultsmentioning

confidence: 99%

Metabonomics study on the hepatoprotective effect mechanism of polysaccharides from different processed products of Angelica sinensis on layer chickens based on UPLC–Q/TOF–MS/MS, multivariate statistical analysis and conjoint analysis

et al. 2022

Biomedical Chromatography

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Chicken colibacillosis is one of the most severe diseases in the poultry industry.Ceftiofur sodium (CS) is often used to treat it in clinical practice and lipopolysaccharide (LPS) accumulates in the chicken's body. Previous experimental studies found that CS combined with LPS could induce liver injury in layer chickens, and polysaccharides from charred Angelica sinensis(CASP) had a better hepatoprotective effect than polysaccharides from unprocessed Angelica sinensis(UASP). However, the intervention mechanism was unclear. Thus, UPLC-Q/TOF-MS/MS-based metabonomics and transcriptomics were used in this study to clarify the hepatoprotective effect mechanism of CASP and UASP in layer chickens. Transcriptomics and enzyme-linked immunosorbent assay were used for biological verification of some critical mutual metabolic pathways screened with metabonomics. The comprehensive analysis results showed that in a layer chicken liver injury model built with LPS and CS, 12 critical metabolic pathways were disturbed, involving 10 important differential metabolites. The hepatoprotective effect mechanism of CASP is related to the arachidonic acid metabolism and mTOR signaling pathways, involving nine important differential metabolites. In contrast, the hepatoprotective effect mechanism of UASP is related to the arachidonic acid metabolism pathway, involving six important differential metabolites.layer chickens, liver injury, LPS, metabonomics, polysaccharides from charred Angelica sinensis (CASP), polysaccharides from unprocessed Angelica sinensis(UASP)Abbreviations: ALT, alanine aminotransferase; AS, Angelica sinensis; AST, aspartate aminotransferase; CASP, polysaccharides from charred Angelica sinensis; CC, chicken colibacillosis; CS, ceftiofur sodium; FC, fold change; LPS, lipopolysaccharide; PLS-DA, partial least squares-discriminant analysis; UASP, polysaccharides from unprocessed AS; UPLC-Q/TOF-MS/MS, ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry/mass spectrometry; VIP, variable importance in projection; VN, Venn.

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“…Then, lecithin indirectly affects the arachidonic acid metabolism, and the increase tendency of the 15(S)-HPETE is the same as lecithin. As we all know, arachidonic acid metabolism is related to the inflammation, and there are many studies indicated that inhibit inflammation could reduce cholestasis (Lu et al, 2014). Lecithin also indirectly affects glycine, serine and threonine metabolism, purine metabolism, and sphingolipid metabolism and eventually indirectly affects the Kreb's cycle.…”

Section: Discussionmentioning

confidence: 99%

Serum Metabolomic Profiling in a Rat Model Reveals Protective Function of Paeoniflorin Against ANIT Induced Cholestasis

Chen

Zhu

Yan

et al. 2016

Phytotherapy Research

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Cholestasis is a leading cause of hepatic accumulation of bile acids resulting in liver injury, fibrosis, and liver failure. Paeoniflorin displays bright prospects in liver protective effect. However, its molecular mechanism has not been well-explored. This study was designed to assess the effects and possible mechanisms of paeoniflorin against alpha-naphthylisothiocyanate-induced liver injury. Ultraperformance liquid chromatography coupled with quadrupole time-of-flight combined with principle component analysis and partial least squares discriminant analysis were integrated to obtain differentiating metabolites for the pathways and clarify mechanisms of disease. The results indicated that paeoniflorin could remarkably downregulate serum biochemical indexes and alleviate the histological damage of liver tissue. Different expression of 14 metabolites demonstrated that paeoniflorin mainly regulated the dysfunctions of glycerophospholipid metabolism and primary bile acid biosynthesis. Moreover, several pathways such as arginine and proline metabolism, ether lipid metabolism, and arachidonic acid metabolism were also related to the efficacy. In conclusion, paeoniflorin has indicated favorable pharmacological effect on serum biochemical indexes and pathological observation on cholestatic model. And metabolomics is a promising approach to unraveling hepatoprotective effects by partially regulating the perturbed pathways, which provide insights into mechanisms of cholestasis.

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Integrated systems toxicology approaches identified the possible involvement of ABC transporters pathway in erythromycin estolate-induced liver injury in rat

Cited by 15 publications

References 57 publications

High-content screening imaging and real-time cellular impedance monitoring for the assessment of chemical’s bio-activation with regards hepatotoxicity

High-content screening imaging and real-time cellular impedance monitoring for the assessment of chemical’s bio-activation with regards hepatotoxicity

Metabonomics study on the hepatoprotective effect mechanism of polysaccharides from different processed products of Angelica sinensis on layer chickens based on UPLC–Q/TOF–MS/MS, multivariate statistical analysis and conjoint analysis

Serum Metabolomic Profiling in a Rat Model Reveals Protective Function of Paeoniflorin Against ANIT Induced Cholestasis

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