Saikosaponin D disrupts platelet-derived growth factor-β receptor/p38 pathway leading to mitochondrial apoptosis in human LO2 hepatocyte cells: A potential mechanism of hepatotoxicity

Chen, Li; Zhang, Feng; Kong, Desong; Zhu, Xiaojing; Wang, Aiyun; Zheng, Shizhong

doi:10.1016/j.cbi.2013.08.006

Cited by 35 publications

(30 citation statements)

References 40 publications

(46 reference statements)

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“…SERPINB9 promotes acute inflammatory response to antigenic stimulus, CD48 facilitates the interaction between activated lymphocytes and T‐cell activation, and C1QB interacts with the Fc regions of IgG or IgM antibody to present in immune complexes . Previous studies have indicated that cytokines secreted from activated immune cells promote the activation of HSCs, which leads to liver fibrosis . Similarly, our results showed an enhanced immune response to DMN stimulation.…”

Section: Discussionsupporting

confidence: 88%

Differential Proteomic Analysis of Dimethylnitrosamine (DMN)‐Induced Liver Fibrosis

Liu

Dai

et al. 2017

Proteomics

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Liver fibrosis is a common pathological feature of many chronic liver diseases. To characterize the entire panorama of proteome changes in dimethylnitrosamine (DMN)-induced liver fibrosis, isobaric tags for relative and absolute quantitation (iTRAQ)-based differential proteomic analysis is performed with DMN-induced liver fibrosis rats. A total of 4155 confidently identified proteins are found, with 365 proteins showing significant changes (fold changes of >1.5 or < 0.67, p < 0.05). In metabolic activation, proteins assigned to drug metabolism enzymes (e.g., CYP2D1) change, suggesting that the liver protection mechanism is activated to relieve DMN toxicity. In addition, the altered proteins of immune response and oxidative stress may activate hepatic stellate cells. Glucose metabolism disorder in DMN model rats is demonstrated by a decrease in key enzymes (e.g., ACSL1) in fatty acid metabolism, a tricabolic acid cycle-related enzyme (SDH), glycogenolysis enzyme, and gluconeogenesis enzymes (PC, PCKGC) and by an increase in glycolysis enzymes (e.g., HXK1). Meanwhile, alterations in iron and calcium ion homeostasis proteins are observed. Our results also show that mitochondrial dysfunction may be involved in DMN hepatotoxicity. In conclusion, these altered liver proteins in the DMN model and control rats provide data for understanding the functional mechanism of liver fibrosis.

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Section: Discussionsupporting

confidence: 88%

Differential Proteomic Analysis of Dimethylnitrosamine (DMN)‐Induced Liver Fibrosis

Liu

Dai

et al. 2017

Proteomics

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“…Besides, other researches have shown that benzbromarone could decrease the mitochondrial membrane potential, reduce the enzyme activities in the mitochondria, induce mitochondrial uncoupling, and decrease the adenosine triphosphate (ATP) production, therefore to cause cell apoptosis and necrosis [30, 31]. Some ingredients of Chinese HMs also could induce mitochondrial apoptosis, which could be the underlying mechanism for hepatotoxicity [32]. Some researchers have shown that the adiponectin could alleviate acetaminophen-induced hepatotoxicity by promoting and mediating autophagy of damaged mitochondria [33].…”

Section: Discussionmentioning

confidence: 99%

To Set Up a Logistic Regression Prediction Model for Hepatotoxicity of Chinese Herbal Medicines Based on Traditional Chinese Medicine Theory

Liu

Chen

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Aims. To establish a logistic regression (LR) prediction model for hepatotoxicity of Chinese herbal medicines (HMs) based on traditional Chinese medicine (TCM) theory and to provide a statistical basis for predicting hepatotoxicity of HMs. Methods. The correlations of hepatotoxic and nonhepatotoxic Chinese HMs with four properties, five flavors, and channel tropism were analyzed with chi-square test for two-way unordered categorical data. LR prediction model was established and the accuracy of the prediction by this model was evaluated. Results. The hepatotoxic and nonhepatotoxic Chinese HMs were related with four properties (p < 0.05), and the coefficient was 0.178 (p < 0.05); also they were related with five flavors (p < 0.05), and the coefficient was 0.145 (p < 0.05); they were not related with channel tropism (p > 0.05). There were totally 12 variables from four properties and five flavors for the LR. Four variables, warm and neutral of the four properties and pungent and salty of five flavors, were selected to establish the LR prediction model, with the cutoff value being 0.204. Conclusions. Warm and neutral of the four properties and pungent and salty of five flavors were the variables to affect the hepatotoxicity. Based on such results, the established LR prediction model had some predictive power for hepatotoxicity of Chinese HMs.

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“…Cell culture. The LO2 immortalized healthy human liver cell line (25,26) was obtained from Shanghai Institute of Biochemistry and Cell Biology (Shanghai, China). Cells were cultured in RPMI 1640 medium supplemented with 10% FBS, 100 U/ml penicillin and 100 µg/ml streptomycin.…”

Section: Methodsmentioning

confidence: 99%

Baicalein protects tert-butyl hydroperoxide-induced hepatotoxicity dependent of reactive oxygen species removal

Wang

Tang

et al. 2017

Molecular Medicine Reports

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Baicalein (BA), one of the major bioactive flavonoids isolated from Scutellariae Radix, possesses various pharmacological activities. The present study aimed to investigate the protective effects of BA on tert‑butyl hydroperoxide (t‑BHP)‑induced hepatotoxicity, and to investigate the potential mechanisms in LO2 cells. BA was demonstrated to possess protective properties against t‑BHP injury in LO2 cells, as evidenced by MTT and lactate dehydrogenase assays. BA significantly prevented t‑BHP‑induced depolarization of mitochondrial membrane potential (MMP), decreased the percentage of apoptotic cells caused by t‑BHP, and prevented intracellular reactive oxygen species (ROS) generation in LO2 cells. Furthermore, BA slightly triggered autophagy in LO2 cells, as evidenced by the elevation of LC3‑II expression, while BA combined treatment with an autophagy inhibitor (chloroquine) or activator (rapamycin) did not alter the hepatoprotective properties. In conclusion, BA may possess a hepatoprotective effect against t‑BHP‑induced liver cell injury, dependent on ROS removal. Therefore, BA may represent a potential drug candidate in protecting hepatotoxicity.

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Saikosaponin D disrupts platelet-derived growth factor-β receptor/p38 pathway leading to mitochondrial apoptosis in human LO2 hepatocyte cells: A potential mechanism of hepatotoxicity

Cited by 35 publications

References 40 publications

Differential Proteomic Analysis of Dimethylnitrosamine (DMN)‐Induced Liver Fibrosis

Differential Proteomic Analysis of Dimethylnitrosamine (DMN)‐Induced Liver Fibrosis

To Set Up a Logistic Regression Prediction Model for Hepatotoxicity of Chinese Herbal Medicines Based on Traditional Chinese Medicine Theory

Baicalein protects tert-butyl hydroperoxide-induced hepatotoxicity dependent of reactive oxygen species removal

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