α‑naphthylisothiocyanate (ANIT) is used to induce intrahepatic cholestasis and it is frequently used for investigations into the disease mechanism. The lithocholic acid (LCA) cholestatic model has also been extensively used in various studies; however, to the best of our knowledge, a comparative study determining the hepatotoxic mechanisms induced by these two models has not been previously conducted. In the present study, ICR mice were treated with ANIT or LCA to induce cholestatic liver injury.
View Article and Find Full Text PDFCholestasis is one of the most challenging diseases to be treated in current hepatology. However little is known about the adaptation difference and the underlying mechanism between acute and chronic cholestasis. In this study, wild-type and Pparα-null mice were orally administered diet containing 0.
View Article and Find Full Text PDFObjectives: Metabolic syndrome (MS) is the concurrence of at least three of five medical conditions: obesity, high blood pressure, insulin resistance, high serum triglyceride (TG) and low serum high-density lipoprotein levels. While fibrates are used to treat disorders other than the lowering serum TG, the mechanism by which fibrates decrease MS has not been established.
Methods: In this study, wild-type and Ppara-null mice fed a medium-fat diet (MFD) were administered gemfibrozil and fenofibrate for 3 months respectively, to explore the effect and action mechanism.
α-Naphthylisothiocyanate (ANIT) is an experimental agent used to induce intrahepatic cholestasis. The Ppara-null mouse line is widely employed to explore the physiological and pathological roles of PPARα. However, little is known about how PPARα influences the hepatotoxicity of ANIT.
View Article and Find Full Text PDFGemfibrozil is a fibrate drug used widely for dyslipidemia associated with atherosclerosis. Clinically, both gemfibrozil and its phase II metabolite gemfibrozil 1-O-β-glucuronide (gem-glu) are involved in drug-drug interaction (DDI). But the DDI risk caused by gem-glu between human and mice has not been compared.
View Article and Find Full Text PDFBackground And Purpose: Fenofibrate, a PPARα agonist, is the most widely prescribed drug for treating hyperlipidaemia. Although fibrate drugs are reported to be beneficial for cholestasis, their underlying mechanism has not been determined.
Experimental Approach: Wild-type mice and Pparα-null mice were pretreated orally with fenofibrate for 3 days, following which α-naphthylisothiocyanate (ANIT) was administered to induce cholestasis.