Cholestatic models induced by lithocholic acid and α-naphthylisothiocyanate: Different etiological mechanisms for liver injury but shared jnk/stat3 signaling

Abstract

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. Biochemical analysis was used to determine the serum. alanine aminotransferase (alT), aspartate aminotransferase (aST), alkaline phosphatase (alP) and total bile acid (TBa) levels, and histopathological assessment was used to examine the liver tissue. Metabolomic analysis was used for the serum biomarker identification. reverse transcription-quantitative Pcr analysis and western blotting were used to analyze the inflammation biomarkers. The serum metabolome of the aniT group clustered away from of the lca group, which was demonstrated by the different modifications of the BA components. ALP level was found to be preferentially increased in the aniT group from 24 to 48 h. Total Ba levels was only increased in the aniT group at 24 h. in contrast, aST and alT activity levels were preferentially increased in the lca group. The bile ducts in the hepatic tissues of the aniT group were observed to be severely dilated, whereas the presence of edematous hepatocytes around the necrotic lesions and neutrophil infiltration were identified in the lca group. The expression levels of cholesterol 7α‑hydroxylase and sterol 12α‑hydroxylase genes were significantly downregulated in the ANIT group compared with the lca group, where a stronger adaptation