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Our recent study revealed that treatment with rodent\u2010specific PXR agonist pregnenolone\u201016\u03b1\u2010carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two\u2010thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver. Here, we investigated the metabolism activity of CYP1A2, CYP3A1\/2 and CYP2C6\/11 during PXR activation\u2010induced liver enlargement and regeneration in rats after cocktail dosing of CYP probe drugs. For PCN\u2010induced hepatomegaly, a notable increase in the metabolic activity of CYP3A1\/2 and CYP2C6\/11, as evidenced by the plasma exposure of probe substrates and the AUC ratios of the characteristic metabolites to its corresponding probe substrates. The metabolic activity of CYP1A2, CYP3A1\/2 and CYP2C6\/11 decreased significantly after PHx. However, PCN treatment obviously enhanced the metabolic activity of CYP2C6\/11 and CYP3A1\/2 in PHx rats. Furthermore, the protein expression levels of CYP3A1\/2 and CYP2C6\/11 in liver were up\u2010regulated. Taken together, this study demonstrates that PXR activation not only induces hepatomegaly and liver regeneration in rats, but also promotes the protein expression and metabolic activity of the PXR downstream metabolizing enzymes such as CYP3A1\/2 and CYP2C6\/11 in the body.<\/jats:p>","DOI":"10.1111\/bcpt.14041","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T07:06:45Z","timestamp":1718694405000},"page":"148-163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pregnane X receptor activation induces liver enlargement and regeneration and simultaneously promotes the metabolic activity of CYP3A1\/2 and CYP2C6\/11 in rats"],"prefix":"10.1111","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5136-0388","authenticated-orcid":false,"given":"Guofang","family":"Bi","sequence":"first","affiliation":[{"name":"NMPA Key Laboratory for Research and Evaluation of Drug Metabolism &amp; 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