New Approach Methods for Hazard Identification: A Case Study with Azole Fungicides Affecting Molecular Targets Associated with the Adverse Outcome Pathway for Cholestasis.

ABSTRACT: Triazole fungicides such as propiconazole (Pi) or tebuconazole (Te) show hepatotoxicity in vivo, e.g., hypertrophy and vacuolization of liver cells following interaction with nuclear receptors such as PXR (pregnane-X-receptor) and CAR (constitutive androstane receptor). Accordingly, azoles affect gene expression associated with these adverse outcomes in vivo but also in human liver cells in vitro. Additionally, genes indicative of liver cholestasis are affected in vivo and in vitro. We therefore analyzed the capability of Pi and Te to cause cholestasis in an adverse outcome pathway (AOP)-driven approach in hepatic cells of human origin in vitro, considering also previous in vivo studies. Bile salt export pump (BSEP) activity assays confirmed that both azoles are weak inhibitors of BSEP. Th

SUBMITTER: Knebel C 

PROVIDER: S-EPMC9600068 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature