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The influence of quercetin (flavonoid) on the bioactivation of paracetamol to NAPQI was investigated using rat liver microsomes and rats in vivo. Paracetamol (80\u00a0mg\/kg) was administered orally without or with silymarin (100\u00a0mg\/kg), a known inhibitor of CYP2E1, CYP3A4 and quercetin (10 and 20\u00a0mg\/kg) to rats for 15 consecutive days. Area under the plasma concentration\u2013time curve (AUC<jats:sub>0\u2010\u221e<\/jats:sub>) and the peakplasma concentration (C<jats:sub>max<\/jats:sub>) of paracetamol were dose\u2010dependently increased with quercetin (10 and 20\u00a0mg\/kg) compared to paracetamol control group (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). On the other hand, the AUC<jats:sub>0\u2010\u221e<\/jats:sub> and C<jats:sub>max<\/jats:sub> of NAPQI were decreased significantly with quercetin. The same results were observed with silymarin also. The elevated liver and kidney functional enzymes\/compounds were significantly reduced by quercetin and silymarin compared to paracetamol control group. The formation of NAPQI was reduced in the incubation samples in presence of quercetin in experiment using isolated rat hepatocytes. The presentstudy results revealed that quercetin might be inhibited the CYP2E1\u2010mediated metabolism of paracetamol; thereby decreased the formation of NAPQI and protected the liver and kidney.<\/jats:p>","DOI":"10.1002\/ptr.6365","type":"journal-article","created":{"date-parts":[[2019,6,3]],"date-time":"2019-06-03T01:30:06Z","timestamp":1559525406000},"page":"1770-1783","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Quercetin reduced the formation of <i>N<\/i>\u2010acetyl\u2010<i>p<\/i>\u2010benzoquinoneimine, a toxic metabolite of paracetamol in rats and isolated rat hepatocytes"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6265-139X","authenticated-orcid":false,"given":"Ravindrababu","family":"Pingili","sequence":"first","affiliation":[{"name":"Research and Development, Department of Pharmacy Jawaharlal Nehru Technological University  Kakinada India"},{"name":"Department of Pharmacology KVSR Siddhartha College of Pharmaceutical Sciences  Vijayawada India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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