{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T16:02:57Z","timestamp":1784217777119,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Current research on infant cholestatic liver injury relies predominantly on adult animal models, with a notable absence of studies using cholestatic liver injury models in infant rats under 3\u2009weeks of age. This study employed infantile Sprague\u2013Dawley (SD) rats as the research subjects and established an acute cholestatic liver injury model via intragastric administration of varying doses of alpha\u2010naphthyl isothiocyanate (ANIT). Forty 11\u2010day\u2010old SD rats were randomly numbered and divided into the following groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098 per group): control group, olive oil group, low\u2010dose group (ANIT\u2010L, 20\u2009mg\/kg), medium\u2010dose group (ANIT\u2010M, 40\u2009mg\/kg), and high\u2010dose group (ANIT\u2010H, 80\u2009mg\/kg). The model was validated by evaluating changes in body weight gain, liver biochemical indices, hepatic histopathology, and immunohistochemical markers. The model group showed slower or even negative weight gain compared to the control group, and the mortality rate of the ANIT (80\u2009mg\/kg) group was 40%. ANIT induced dose\u2010dependent acute cholestatic injury in infant rats. Model groups showed significantly elevated liver enzymes, TBA, and bilirubin, positively correlating with ANIT dose. Transcriptionally, bile salt export pump (BSEP) increased and Na+\/taurocholate cotransporter (NTCP) decreased, correlating positively and negatively with dose, respectively. Protein expression mirrored that BSEP and farnesoid X receptor (FXR) increased, NTCP and 7\u03b1\u2010hydroxylase (CYP7A1) decreased, all showing significant dose correlations. In conclusion, a medium dose (40\u2009mg\/kg) of ANIT likely represents the optimal dose for inducing acute cholestatic liver injury, reflecting hepatic damage, histopathological alterations, and disruptions in the FXR\/CYP7A1 and BSEP\/NTCP signaling axes.\n                  <\/jats:p>","DOI":"10.1002\/jat.70344","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:02:57Z","timestamp":1784214177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishing Alpha\u2010Naphthyl Isothiocyanate\u2010Induced Infant Rat Cholestatic Liver Injury Model: Concomitant Alterations in FXR\/CYP7A1 and BSEP\/NTCP Signaling Axes"],"prefix":"10.1002","author":[{"given":"Ning","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Dalian Medical University  Dalian Liaoning 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