Promising toxicological biomarkers for the diagnosis of liver injury types: Bile acid metabolic profiles and oxidative stress marker as screening tools in drug development.

摘要: Promising biomarkers were identified in adult male Crl:CD (SD) rats for the screening of new chemical entities their potential to cause liver injury. We examined serum biochemistry, histopathology, and bile acid profiles by LC-MS/MS, mRNA expression transporters CYPs an RT-PCR after following treatments rats: (a) duct ligation (BDL); (b) a single oral dose 150 mg/kg α-naphthylisothiocyanate (ANIT); (c) repeated doses novel pyrrolidinecarboxylic derivative (abbreviated as PCA) at 30, 300, 1000 mg/kg. The total levels bilirubin concentrations found be elevated all groups. However, component PCA group differed significantly from BDL ANIT models: deoxycholic acid, lithocholic sulfated acids upregulated dose-dependent manner only group. In addition, demonstrated high hepatic heme oxygenase-1 expression, whereas groups similar. histopathological findings, both groups, hyperplasia, hepatocyte degeneration necrosis. contrast, hyperplasia observed group, even lethal dose. These results indicated that induced cholestatic condition increase oxidative stress markers implies this will also lead hepatocellular conclusion, components levels, could provide information aids diagnosis injury type helps elucidate mechanisms hepatotoxicity. findings can extrapolated into our clinical investigation. analysis these crucial is likely useful tool optimization phase drug discovery.