Early indications of ANIT-induced cholestatic liver injury: Alteration of hepatocyte polarization and bile acid homeostasis

Yang, Tingting; Mei, Huifang; Xu, Dengqiu; Wang, Zhou; Zhu, Xiaoyu; Sun, Lixin; Huang, Xin; Wang, Xue; Shu, Ting; Liu, Jia; Ding, Jiaxin; Hassan, Hozeifa Mohamed; Zhang, Luyong; Jiang, Zhenzhou

doi:10.1016/j.fct.2017.09.051

Cited by 35 publications

(22 citation statements)

References 42 publications

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“…Accumulating studies have shown that oral quercetin treatment can significantly reduce plasma total cholesterol (T‐CHO) level in diabetic animal models (Eitah et al, ; Latifi, Mohammadpour, Fathi, & Nourani, ; Zhang, Dong, Wang, & Zhang, ). Being synthesized from cholesterol in the liver, bile acids (BAs) represents a major pathway for the elimination of steroids from the body (Chavez‐Talavera, Tailleux, Lefebvre, & Staels, ; T. Yang, Khan, et al, ; Yang et al, ). Besides the promotion of fat‐soluble nutrients absorption, BAs also participate in many metabolic processes, including glucose, lipids, and energy homeostasis by acting as physiological small molecule scavengers and signaling molecules.…”

Section: Introductionmentioning

confidence: 99%

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Yang

Cai

et al. 2019

Phytotherapy Research

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189

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Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM‐induced NAFLD were investigated. T2DM‐induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM‐induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM‐induced production of interleukin 1 beta, interleukin 6, and TNF‐α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM‐induced NAFLD. In high D‐glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM‐induced NAFLD.

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Section: Introductionmentioning

confidence: 99%

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Yang

Cai

et al. 2019

Phytotherapy Research

Self Cite

189

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“…Wenfang Tian et al (2016) also found that WDR5 is an important epigenetic factor in the process of liver fibrosis. S1PR1 has been reported to be associated with cholestatic liver injury in early stage liver cancer and may be a potential target for the prevention of drug-induced cholestatic liver injury (Yang et al, 2017). HMGA1 was confirmed to be involved in the proliferation and invasion of HCC cells through the ilk/Akt/GSK3 signaling pathway (Liu et al, 2017).…”

Section: The Hcc Progression Lncrnas Identified With Machine Learningmentioning

confidence: 97%

Identification and Analysis of the Blood lncRNA Signature for Liver Cirrhosis and Hepatocellular Carcinoma

Xia

Shu

et al. 2020

Front. Genet.

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As one of the most common malignant tumors, hepatocellular carcinoma (HCC) is the fifth major cause of cancer-associated mortality worldwide. In 90% of cases, HCC develops in the context of liver cirrhosis and chronic hepatitis B virus (HBV) infection is an important etiology for cirrhosis and HCC, accounting for 53% of all HCC cases. To understand the underlying mechanisms of the dynamic chain reactions from normal to HBV infection, from HBV infection to liver cirrhosis, from liver cirrhosis to HCC, we analyzed the blood lncRNA expression profiles from 38 healthy control samples, 45 chronic hepatitis B patients, 46 liver cirrhosis patients, and 46 HCC patients. Advanced machine-learning methods including Monte Carlo feature selection, incremental feature selection (IFS), and support vector machine (SVM) were applied to discover the signature associated with HCC progression and construct the prediction model. One hundred seventy-one key HCC progression-associated lncRNAs were identified and their overall accuracy was 0.823 as evaluated with leave-one-out cross validation (LOOCV). The accuracies of the lncRNA signature for healthy control, chronic hepatitis B, liver cirrhosis, and HCC were 0.895, 0.711, 0.870, and 0.826, respectively. The 171-lncRNA signature is not only useful for early detection and intervention of HCC, but also helpful for understanding the multistage tumorigenic processes of HCC.

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“…ANIT, a hepatotoxic agent that is widely used to induce intrahepatic cholestasis in rodents, leads to cholestasis by impairing parenchymal hepatic cell polarization, directly injuring biliary epithelial cells and inhibiting BA transporter function and expression [32]. According to the literature, treating rats with ANIT significantly decreases bile flow, and cotreatment with ANIT and 18b-GA significantly increases bile flow [10].…”

Section: Discussionmentioning

confidence: 99%

18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway

Cui

Wang

et al. 2018

Acta Pharmacol Sin

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Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18β-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect. According to the results, 18b-GA markedly attenuated ANIT-induced liver injury as indicated the hepatic plasma chemistry index and histopathology examination. In addition, the expression levels of nuclear factors, including Sirt1, FXR and Nrf2, and their target efflux transporters in the liver, which mainly mediate bile acid homeostasis in hepatocytes, significantly increased. Furthermore, we first revealed that 18b-GA treatment significantly activated FXR, and which can be significantly reduced by EX-527 (a potent and selective Sirt1 inhibitor), indicating that 18b-GA activates FXR through Sirt1. Taken together, 18b-GA confers hepatoprotection against ANIT-induced cholestasis by activating FXR through Sirt1, which promotes gene expression of the efflux transporter, and consequently attenuates dysregulation of bile acid homeostasis in hepatocyte compartments.

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Early indications of ANIT-induced cholestatic liver injury: Alteration of hepatocyte polarization and bile acid homeostasis

Cited by 35 publications

References 42 publications

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Identification and Analysis of the Blood lncRNA Signature for Liver Cirrhosis and Hepatocellular Carcinoma

18β-Glycyrrhetinic acid protects against alpha-naphthylisothiocyanate-induced cholestasis through activation of the Sirt1/FXR signaling pathway

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