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Mice were orally administrated with Tan IIA (10 or 30\u2009mg\/kg\/day) for 1\u2009week and subsequently gavaged with 200\u2009mg\/kg of APAP. Tan IIA reduced APAP\u2010induced nephrotoxicity as evidenced by histopathological evaluation and serum creatinine levels. Tan IIA pretreatment promoted the efflux of the toxic intermediate metabolite <jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:italic>p<\/jats:italic>\u2010benzoquinone imine (NAPQI), thus reduced its injury to mouse kidney. After Tan IIA pretreatment, a remarkable increase in mRNA and protein expression of Nrf2 and its target genes Mrp2 and Mrp4 was observed in Nrf2<jats:sup>+\/+<\/jats:sup> mice kidneys, however, no obvious change of Mrp2 and Mrp4 mRNA and protein expression was detected in Nrf2<jats:sup>\u2212\/\u2212<\/jats:sup> mice kidneys. HK\u20102 cells were used for exploring the roles of Tan IIA in the Nrf2\u2010MRPs pathway in vitro. Consistently, Tan IIA up\u2010regulated the Nrf2\u2010MRPs pathway and promoted the nuclear Nrf2 accumulation in HK\u20102 cells. Collectively, our findings suggested that Tan IIA facilitated the clearance of toxic intermediate metabolite NAPQI from the kidney through upregulation of the Nrf2\u2010MRP2\/4 pathway, thereby, performing preventive effects against APAP\u2010induced nephrotoxicity.<\/jats:p>","DOI":"10.1002\/tox.23511","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T07:05:48Z","timestamp":1646377548000},"page":"1618-1628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Tanshinone <scp>IIA<\/scp> prevents acetaminophen\u2010induced nephrotoxicity through the activation of the <scp>Nrf2\u2010Mrp2<\/scp>\/4 pathway in mice"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4486-8042","authenticated-orcid":false,"given":"Xiqian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Third People's Hospital of Chengdu &amp; College 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