Prevention by dietary (n-6) polyunsaturated phosphatidylcholines of intrahepatic cholestasis induced by cyclosporine A in animals

Chanussot, F.; Benkoël, L

doi:10.1016/s0024-3205(03)00292-3

Cited by 10 publications

(5 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, we observed that CsA down-regulated another BA transporter, Mrp2 (Abcc2). These data are in line with observations made in rats showing that the same transporters were down-regulated by CsA in the liver at the protein level [34]. With regard to CPZ we detected down-regulation of Fxr targets such as Bsep, Mdr3, Ntcp (Slc10a1), and Cyp8b1.…”

Section: Discussionsupporting

confidence: 92%

Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes

Szalowska¹,

Stoopen²,

Groot³

et al. 2013

BMC Med Genomics

View full text Add to dashboard Cite

BackgroundUnexpected cholestasis substantially contributes to drug failure in clinical trials. Current models used for safety assessment in drug development do not accurately predict cholestasis in humans. Therefore, it is of relevance to develop new screening models that allow identifying drugs with cholestatic properties.MethodsWe employed mouse precision cut liver slices (PCLS), which were incubated 24 h with two model cholestatic compounds: cyclosporin A (CsA) and chlorpromazine (CPZ). Subsequently, transcriptome analysis using DNA microarrays and q-PCR were performed to identify relevant biological processes and biomarkers. Additionally, histology was carried out and levels of triglycerides (TG) and bile acids (BA) were measured. To verify the ex vivo mouse data, these were compared with publically available human data relevant for cholestasis.ResultsWhole genome gene expression analysis showed that CsA up-regulated pathways related to NF-κB, ER stress and inflammation. Both CsA and CPZ down-regulated processes related to extracellular matrix (ECM) remodelling, BA homeostasis, Fxr signalling, and energy metabolism. The differential expression of a number of characteristic genes (e.g. Abcg5, Abcg8, Klf15, and Baat) could be confirmed by q-PCR. Histology revealed that CsA but not CPZ induced “ballooning” of hepatocytes. No effects on TG and BA levels were observed after incubation of PCLS with CsA and CPZ. A substantial number of processes altered in CsA- and CPZ-treated mouse PCLS ex vivo was also found to be affected in liver biopsies of cholestatic patients.ConclusionThe present study demonstrated that mouse PCLS can be used as a tool to identify mechanisms of action of cholestatic model compounds. The induction of general stress responses and down-regulated Fxr signalling could play a role in the development of drug induced cholestasis. Importantly, comparative data analysis showed that the ex vivo mouse findings are also relevant for human pathology. Moreover, this work provides a set of genes that are potentially useful to assess drugs for cholestatic properties.

show abstract

Section: Discussionsupporting

confidence: 92%

Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes

Szalowska¹,

Stoopen²,

Groot³

et al. 2013

BMC Med Genomics

View full text Add to dashboard Cite

show abstract

“…The therapeutic effect of oral PP could be due to increased collagenase activity. In addition, effects of PP on transaminases, Na, K-ATPase, and Ca, Mg-ATPase have been demonstrated [2][3][4]13].…”

Section: Original Researchmentioning

confidence: 99%

Polyunsaturated Phosphatidylcholine Protects Against Wound Contraction in Experimental Skin Burn Injury

Kanmaz

Karakayalı

Sakallioglu

et al. 2004

Journal of Investigative Surgery

View full text Add to dashboard Cite

Polyunsaturated phosphatidylcholine (PP) is a soybean lecithin, whose oral supplementation prevents fibrosis and strictures in animal models. The purpose of the present study was to investigate the effect of PP on wound contraction using a model of skin burn injury. Thirty male Sprague-Dawley rats were randomly divided into three groups: control (C), just burn (JB), and burn treated with PP (BPP). Burns were induced on the dorsum of the rats by a metal plate with a 4-cm(2) contact surface. Ten percent emulsion of PP was given orally for 21 days in BPP group. The effects of PP on burns were evaluated histologically on day 21, and wound contraction was measured by planimetry weekly. Microscopic evaluation included the amount and density of myofibroblasts and collgen type III, the existence of mature collagen fibers in the regenerated dermis, and thickness measurements of the regenerated tissue. There was a significant decrease in mean wound size index in group JB when compared to BPP on days 14 and 21 (p <.05 and p <.01, respectively). After 3 weeks, the granulation tissue was more cell dense, containing high numbers of myofibroblasts in group JB when compared to BPP (p <.05). The wounds had more mature collagen bundles, but less collagen type III in group BPP when compared to JB. Thus, polyunsaturated phospatidylcholine protected against wound contraction and modulated wound healing in the rat model of skin burn injury.

show abstract

“…They found phosphatidylcholines were required in the bile secrete process to form vesicles enriched in cholesterol. The protective effect of phosphatidylcholines could possibly be originated from the activation of multidrug export pump 1 (MDR1), which protects the hepatocyte by returning hydrophobic toxic bile components to the bile ( Muller and Jansen, 1998 ; Chanussot and Benkoël, 2003 ).…”

Section: Hepatoprotective Agents In the Management Of Icpmentioning

confidence: 99%

Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects

Shan,

Dai,

Chen

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Intrahepatic cholestasis of pregnancy (ICP) is characterized by unexplained distressing pruritus in the mother and poses significant risk to the fetus of perinatal mortality. Occurring in the second and third trimester, the serum bile acid and aminotransferase are usually elevated in ICP patients. Ursodeoxycholic acid (UDCA) is the first line drug for ICP but the effectiveness for hepatoprotection is to a certain extent. In ICP patients with severe liver damage, combination use of hepatoprotective agents with UDCA is not uncommon. Herein, we reviewed the current clinical evidence on application of hepatoprotective agents in ICP patients. The underlying physiological mechanisms and their therapeutic effect in clinical practice are summarized. The basic pharmacologic functions of these hepatoprotective medications include detoxification, anti-inflammation, antioxidation and hepatocyte membrane protection. These hepatoprotective agents have versatile therapeutic effects including anti-inflammation, antioxidative stress, elimination of free radicals, anti-steatohepatitis, anti-fibrosis and anti-cirrhosis. They are widely used in hepatitis, non-alcoholic fatty liver disease, drug induced liver injury and cholestasis. Evidence from limited clinical data in ICP patients demonstrate reliable effectiveness and safety of these medications. Currently there is still no consensus on the application of hepatoprotective agents in ICP pregnancies. Dynamic monitoring of liver biochemical parameters and fetal condition is still the key recommendation in the management of ICP pregnancies.

show abstract

Prevention by dietary (n-6) polyunsaturated phosphatidylcholines of intrahepatic cholestasis induced by cyclosporine A in animals

Cited by 10 publications

References 58 publications

Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes

Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes

Polyunsaturated Phosphatidylcholine Protects Against Wound Contraction in Experimental Skin Burn Injury

Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects

Contact Info

Product

Resources

About