A metabonomic analysis of the effect of quercetin on toxicity induced by chronic exposure to low-level dichlorvos in rat plasma

Zeng, Yan; Qı, Lei; Li, Sifan; Hou, Yurong; Wang, Xu; Wang, Hong; Zhao, Xiujuan; Sun, Chongde

doi:10.1039/c4mb00299g

Cited by 11 publications

(5 citation statements)

References 51 publications

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“…In addition, we found that the protein expression levels of NF-κB and Bax in the propofol group were significantly lower than those in the model group rats, and the Bcl-2 protein expression levels were significantly higher in the propofol group. These findings agree with the results of a study showing that quercetin reduces apoptosis of myocardial cells through downregulating the expression of Bax and upregulating the expression of Bcl-2 ( 26 ). Finally, the direct observation of the myocardial injury in the rat hearts by H&E staining proved that the myocardium of rats in the model group presented clear damage, while that of rats in the propofol group was much less injured.…”

Section: Discussionsupporting

confidence: 92%

Propofol protects against endotoxin-induced myocardial injury by inhibiting NF-κB-mediated inflammation

et al. 2017

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This study investigated whether propofol protects against endotoxin-induced myocardial injury by inhibiting NF-κB-mediated inflammation. Thirty clean male SD rats were randomly divided into a control (n=10), a model (n=10) and a propofol group (n=10). The model and propofol groups were injected with lipopolysaccharide (LPS) via the caudal vein to establish animal models of myocardial injury. At the same time, the control group was injected with normal saline via the caudal vein. At 30 min after the injections, the propofol group was treated with a continuous intravenous infusion of propofol, the control and model groups were injected with normal saline, and the three groups were treated continuously for 4 h. The changes in levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum were detected via enzyme-linked immunosorbent assay (ELISA). The mRNA expression level of nuclear factor-κB (NF-κB) in myocardial tissues was detected via quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of NF-κB, Bax and Bcl-2 in atrial muscles in each group were measured via Western blotting. The damage of myocardial tissues was detected via hematoxylin eosin (H&E) staining of tissues. Our results showed that compared with those in control group, the levels of IL-1, IL-6 and TNF-α in serum in the model and propofol groups were significantly higher; however, the levels in the model group, were significantly higher than those in the propofol group (P<0.01). The mRNA and protein expression levels of NF-κB in the propofol group were significantly lower than those in the model group (P<0.01). Likewise, the protein expression levels of Bax were significantly lower, while those of Bcl-2 were significantly increased. H&E staining showed that the myocardial tissues in the model group were damaged significantly, but the damage in the propofol group was significantly less severe. Based on our findings, it seems propofol can indeed protect against endotoxin-induced myocardial injury through its inhibition of the NF-κB-mediated inflammatory pathway.

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Section: Discussionsupporting

confidence: 92%

Propofol protects against endotoxin-induced myocardial injury by inhibiting NF-κB-mediated inflammation

et al. 2017

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“…Metabolomics is a systemic global quantitative assessment for the comprehensive analysis of changes in endogenous metabolites in a biological matrix, which can be directly coupled to biological phenotypic responses to a disease 11 12 , drug treatment 13 14 or intervention 15 . Based on metabolite perturbations following a stroke, one can map all of the pathways related to ischemic stroke; understanding these pathways is among the key challenges facing cerebral ischemia research.…”

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confidence: 99%

System-wide assembly of pathways and modules hierarchically reveal metabolic mechanism of cerebral ischemia

Zhu

Guo

Zhang

et al. 2015

Sci Rep

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The relationship between cerebral ischemia and metabolic disorders is poorly understood, which is partly due to the lack of comparative fusing data for larger complete systems and to the complexity of metabolic cascade reactions. Based on the fusing maps of comprehensive serum metabolome, fatty acid and amino acid profiling, we identified 35 potential metabolic biomarkers for ischemic stroke. Our analyses revealed 8 significantly altered pathways by MetPA (Metabolomics Pathway Analysis, impact score >0.10) and 15 significantly rewired modules in a complex ischemic network using the Markov clustering (MCL) method; all of these pathways became more homologous as the number of overlapping nodes was increased. We then detected 24 extensive pathways based on the total modular nodes from the network analysis, 12 of which were new discovery pathways. We provided a new perspective from the viewpoint of abnormal metabolites for the overall study of ischemic stroke as well as a new method to simplify the network analysis by selecting the more closely connected edges and nodes to build a module map of stroke.

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“…We speculate that it was probably related to the PLA2 activation. Endogenous lysoPCs have important functions in maintaining homeostasis in organisms, that is, the product of low-density lipoprotein (LDL) oxidation can be oxidized by a series of factors, including free radicals [39]. LysoPE (0:0/20:4), the degradation product of PE, has an important function in membrane structure and energy reserves.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Hepatotoxicity of the Zhi-Zi-Hou-Po Decoction by Combining UPLC-Q-Exactive-MS-Based Metabolomics and HPLC-MS/MS-Based Geniposide Tissue Distribution

Wang

Fěng

2019

Molecules

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With traditional Chinese medicine (TCM) becoming widespread globally, its safety has increasingly become a concern, especially its hepatoxicity. For example, Gardenia jasminoides Ellis is a key ingredient in the Zhi-Zi-Hou-Po decoction (ZZHPD), which is a commonly-used clinically combined prescription of TCM that may induce hepatoxicity. However, the underlying toxicity mechanism of ZZHPD is not fully understood. In this study, a plasma metabolomics strategy was used to investigate the mechanism of ZZHPD-induced hepatotoxicity through profiling entire endogenous metabolites. Twenty-four Sprague-Dawley rats were randomly assigned into four groups, which were orally administered with 0.9% saline, as well as 2.7 g/kg/day, 8.1 g/kg/day, or 27 g/kg/day of ZZHPD for 30 consecutive days, respectively. Biochemical assay and metabolomics assay were used to detect serum and plasma samples, whilst histopathological assay was used for detecting liver tissues, and the geniposide distribution in tissues was simultaneously measured. The results showed that the concentration of 20 metabolites linked to amino acid, lipid, and bile acid metabolism had significant changes in the ZZHPD-treated rats. Moreover, toxic effects were aggravated with serum biochemical and histopathological examines in liver tissues as the dosage increased, which may be associated with the accumulation of geniposide in the liver as the dosage increased. Notably, our findings also demonstrated that the combined metabolomics strategy with tissue distribution had significant potential for elucidating the mechanistic complexity of the toxicity of TCM.

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A metabonomic analysis of the effect of quercetin on toxicity induced by chronic exposure to low-level dichlorvos in rat plasma

Cited by 11 publications

References 51 publications

Propofol protects against endotoxin-induced myocardial injury by inhibiting NF-κB-mediated inflammation

Propofol protects against endotoxin-induced myocardial injury by inhibiting NF-κB-mediated inflammation

System-wide assembly of pathways and modules hierarchically reveal metabolic mechanism of cerebral ischemia

Evaluation of the Hepatotoxicity of the Zhi-Zi-Hou-Po Decoction by Combining UPLC-Q-Exactive-MS-Based Metabolomics and HPLC-MS/MS-Based Geniposide Tissue Distribution

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