Match!

Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(−/−) mice

Published on Sep 1, 2015in European Journal of Pharmacology3.17
· DOI :10.1016/j.ejphar.2015.06.008
Su Jong Yu22
Estimated H-index: 22
(SNU: Seoul National University),
Seyeon Bae11
Estimated H-index: 11
(SNU: Seoul National University)
+ 7 AuthorsHyo Suk Lee43
Estimated H-index: 43
(SNU: Seoul National University)
Abstract
Abstract Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(−/−) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b + cells in the liver of vitamin C-insufficient Gulo(−/−) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(−/−) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(−/−) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury.
  • References (43)
  • Citations (4)
📖 Papers frequently viewed together
1 Citations
201014.97Hepatology
11 Authors (Jin-Kyu Park, ..., Kyu-Shik Jeong)
38 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References43
Newest
#1Eun Sun Jang (Seoul National University Hospital)H-Index: 16
#2Jung-Hwan Yoon (Seoul National University Hospital)H-Index: 46
Last. Chung Yong Kim (Seoul National University Hospital)H-Index: 31
view all 9 authors...
Purpose The hydrophobic bile acid, deoxycholic acid (DC), can induce apoptosis in hepatocytes. The roles of DC and its transporter are not yet established in hepatocellular carcinoma (HCC) cells. We investigated DC-induced alterations in HCC cell growth, with a particular focus on the effect of the expression of bile acid (BA)-transporting Na+-dependent taurocholic cotransporting polypeptides (NTCPs).
5 CitationsSource
#1Seyeon Bae (SNU: Seoul National University)H-Index: 11
#2Chung-Hyun ChoH-Index: 22
Last. Wang Jae LeeH-Index: 26
view all 9 authors...
Abstract Aim: l-ascorbic acid (vitamin C) insufficiency is considered one of the major risk factors for the development of liver disease. However, its specific effects and related mechanisms in vivo are largely unknown. The objective of this study was to investigate the in vivo protective role of vitamin C and its related mechanisms in liver injury with Gulo(−/−) mice that cannot synthesize vitamin C like humans due to the lack of l-gulonolactone-γ-oxidase (Gulo), an essential enzyme for vitamin...
8 CitationsSource
#1Ariane MallatH-Index: 47
#2Sophie Lotersztajn (French Institute of Health and Medical Research)H-Index: 43
Liver fibrosis is the common scarring reaction associated with chronic liver injury that results from prolonged parenchymal cell injury and/or inflammation. The fibrogenic response is characterized by progressive accumulation of extracellular matrix components enriched in fibrillar collagens and a failure of matrix turnover. This process is driven by a heterogeneous population of hepatic myofibroblasts, which mainly derive from hepatic stellate cells and portal fibroblasts. Regression of fibrosi...
119 CitationsSource
#1Binghua Dai ('SMMU': Second Military Medical University)H-Index: 7
#2Li Geng ('SMMU': Second Military Medical University)H-Index: 7
Last. Jiamei Yang ('SMMU': Second Military Medical University)H-Index: 21
view all 8 authors...
Sustained endoplasmic reticulum (ER) stress has been linked to cell death and the pathogenesis of many liver diseases, including toxic liver, cholestasis, and infectious liver disease. The cellular pathways that attenuate hepatic ER stress have been the focus of many recent studies, but the role of microRNAs (miRNA) in this process remains unknown. Here, we report that one of the most abundant miRNAs in hepatocytes, miR-199a-5p, was elevated in both bile acid- and thapsigargin (TG)-stimulated cu...
44 CitationsSource
#1Hiroyuki Nakashima (National Defense Medical College)H-Index: 17
#2Yoshiko Ogawa (National Defense Medical College)H-Index: 2
Last. Seki Shuhji (National Defense Medical College)H-Index: 36
view all 8 authors...
We have reported that the mouse hepatic injury induced by either α-galactosylceramide (α-GalCer) or bacterial DNA motifs (CpG-ODN) is mediated by the TNF/NKT cell/Fas-ligand (FasL) pathway. In addition, F4/80+ Kupffer cells can be subclassified into CD68+ subset with a phagocytosing capacity and CD11b+ subset with a TNF-producing capacity. CD11b+ subset increase if mice are fed high-fat and cholesterol diet (HFCD). The present study examined how a HFCD affects the function of NKT cells and F4/80...
32 CitationsSource
#1Michael TraunerH-Index: 78
#2Peter J. MeierH-Index: 85
Last. James L. BoyerH-Index: 80
view all 3 authors...
The formation of bile is a vital function, and its impairment by drugs or infectious, autoimmune, metabolic, or genetic disorders results in the syndrome commonly known as cholestasis.1 The secreti...
534 Citations
Cholestasis results in a buildup of bile acids in serum and in hepatocytes. Early studies into the mechanisms of cholestatic liver injury strongly implicated bile acid-induced apoptosis as the major cause of hepatocellular injury. Recent work has focused both on the role of bile acids in cell signaling as well as the role of sterile inflammation in the pathophysiology. Advances in modern analytical methodology have allowed for more accurate measuring of bile acid concentrations in serum, liver, ...
100 CitationsSource
#1Prakash Ramachandran (Edin.: University of Edinburgh)H-Index: 16
#2John P. Iredale (Edin.: University of Edinburgh)H-Index: 61
Liver fibrosis is the generic response to chronic injury of varying aetiologies. A number of common mechanisms link this response to the pathogenesis of fibrosis in other organs. While long thought to be relentlessly progressive, there is now excellent evidence in both human liver disease and animal models that hepatic fibrosis is potentially reversible. The liver therefore provides an excellent bidirectional model for the study of fibrogenesis and fibrosis resolution. In this article, we will r...
67 CitationsSource
#1Joy X. Jiang (UC Davis: University of California, Davis)H-Index: 17
#2Xiangling Chen (UC Davis: University of California, Davis)H-Index: 6
Last. Natalie J. Torok (UC Davis: University of California, Davis)H-Index: 22
view all 9 authors...
Abstract Reactive oxygen species (ROS) play a key role in chronic liver injury and fibrosis. Homologs of NADPH oxidases (NOXs) are major sources of ROS, but the exact role of the individual homologs in liver disease is unknown. Our goal was to determine the role of NOX4 in liver fibrosis induced by bile duct ligation (BDL) with the aid of the pharmacological inhibitor GKT137831, and genetic deletion of NOX4 in mice. GKT137831 was either applied for the full term of BDL (preventive arm) or starte...
137 CitationsSource
#1Yan Jiao (UTHSC: University of Tennessee Health Science Center)H-Index: 14
#2Jifei ZhangH-Index: 2
Last. Weikuan Gu (UTHSC: University of Tennessee Health Science Center)H-Index: 11
view all 9 authors...
The aim of this study was to test the hypothesis that hepatic vitamin C (VC) levels in VC deficient mice rescued with high doses of VC supplements still do not reach the optimal levels present in wild-type mice. For this, we used a mouse scurvy model (sfx) in which the L-gulonolactone oxidase gene (Gulo) is deleted. Six age- (6 weeks old) and gender- (female) matched wild-type (WT) and sfx mice (rescued by administering 500 mg of VC/L) were used as the control (WT) and treatment (MT) groups (n =...
8 CitationsSource
Cited By4
Newest
#1Zhu-Jun Mao (ZJNU: Zhejiang Chinese Medical University)H-Index: 1
#2Min Lin (ZJNU: Zhejiang Chinese Medical University)H-Index: 1
Last. Lu-ping Qin (ZJNU: Zhejiang Chinese Medical University)H-Index: 2
view all 4 authors...
Insulin resistance (IR) is likely to induce metabolic syndrome and type 2 diabetes mellitus (T2DM). Gluconeogenesis (GNG) is a complex metabolic process that may result in glucose generation from certain non-carbohydrate substrates. Chinese herbal medicine astragalus polysaccharides and berberine have been documented to ameliorate IR, and combined use of astragalus polysaccharide (AP) and berberine (BBR) are reported to synergistically produce an even better effect. However, what change may occu...
1 CitationsSource
#1Leonardo Baiocchi (University of Rome Tor Vergata)H-Index: 6
#2Tianhao Zhou (A&M: Texas A&M University)H-Index: 7
Last. Gianfranco Alpini (IUPUI: Indiana University – Purdue University Indianapolis)H-Index: 68
view all 10 authors...
Bile acids are a family of amphipathic compounds predominantly known for their role in solubilizing and absorbing hydrophobic compounds (including liposoluble vitamins) in the intestine. Bile acids also are key signaling molecules and inflammatory agents that activate transcriptional factors and cell signaling pathways that regulate lipid, glucose, and energy metabolism in various human disorders, including chronic liver diseases. However, in the last decade increased awareness has been founded ...
Source
#1Min Luo (NBU: Ningbo University)H-Index: 5
#2Zhen Tan (NBU: Ningbo University)H-Index: 2
Last. Aiming Liu (NBU: Ningbo University)H-Index: 7
view all 12 authors...
Perfluorodecanoic acid (PFDA) is widely used in production of many daily necessities based on their surface properties and stability. It was assigned as a Persistent Organic Pollutant in 2009 and became a public concern partly because of its potential for activation of the peroxisome proliferator-activated receptor alpha (PPARα). In this study, wild-type and Ppara-null mice were administered PFDA (80 mg/kg). Blood and liver tissues were collected and subjected to systemic toxicological and mecha...
6 CitationsSource
#1Erika Ramos-Tovar (CINVESTAV)H-Index: 7
#2Pablo Muriel (CINVESTAV)H-Index: 34
Abstract The leaves of Stevia rebaudiana, a natural sweetener, contain more than 30 different steviol glycosides, of which stevioside (STV) and rebaudioside A are found in major proportion. The main chemistry structures of glycosides found in stevia are diterpenes with strong antioxidant and antiinflammatory properties. Most liver diseases involve nitrogen and oxygen free radicals that attack macromolecules such as lipids, proteins, and nucleic acids for the production and perpetuation of hepati...
9 CitationsSource
#1Naglaa A. Bayomy (Tanta University)H-Index: 6
#2Gehan M. Soliman (Tanta University)H-Index: 3
Last. Eman Z. AbdelazizH-Index: 6
view all 3 authors...
Potassium bromate (KBrO3 ) is a food additive which is used primarily as a maturing agent for flour. It is proved as a toxic agent with significant reduction in the activities of antioxidant capacity. The therapeutic efficacy of vitamin C as antioxidant may provide a possible solution to KBrO3 mediated oxidative damage. Twenty four adult male albino rats were used to evaluate the protective role of vitamin C against KBrO3 induced hepatotoxicity and divided into four groups; Group 1 (control), Gr...
2 CitationsSource