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However, intestinal mucositis is a well\u2010known adverse event of 5\u2010FU, which limits its therapeutic use. Indeed, thymol, which is a monoterpene component of the essential oil derived from thymus, has a potential anti\u2010inflammatory and immunomodulatory activity. Therefore, this study aimed to investigate the potential chemoprotective effect of thymol against 5\u2010FU\u2010induced intestinal mucositis. Rats were either exposed to two doses of 5\u2010FU (150\u2009mg\/kg, ip) and\/or treated with thymol (60 or 120\u2009mg\/kg). Oxidative stress and inflammatory markers, as well as pathological changes, were assessed. 5\u2010FU\u2010induced severe intestinal damages as were evidenced by histopathological changes as well as oxidative and inflammatory responses. Thymol pretreatment inhibited 5\u2010FU\u2010induced oxidative stress by reducing lipid peroxidation and increasing intestinal levels of antioxidant systems. Moreover, inflammatory response markers, such as interleukin\u20106, prostaglandin E2, and COX\u20102 were also improved. The immunoblotting analysis also showed that thymol significantly inhibited the 5\u2010FU\u2010induced expression of nuclear factor\u2010\u03baB, tumor necrosis factor\u2010\u03b1, and transforming growth factor \u03b2\u20101 (TGF\u2010\u03b21), in addition to the suppression of p38 and phosphorylated c\u2010Jun N\u2010terminal kinases (p\u2010JNK) mitogen\u2010activated protein kinase proteins' expressions. Our study is the first to demonstrate the promising protective effect of thymol against 5\u2010FU\u2010induced intestinal mucositis through inhibition of oxidative, inflammatory pathways, and suppression of TGF\u2010\u03b2\/p38\/p\u2010JNK signaling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbt.22932","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T11:11:03Z","timestamp":1634814663000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Thymol ameliorates 5\u2010fluorouracil\u2010induced intestinal mucositis: Evidence of down\u2010regulatory effect on TGF\u2010\u03b2\/MAPK pathways through NF\u2010\u03baB"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-771X","authenticated-orcid":false,"given":"Layla A.","family":"Al\u2010Khrashi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, KSU  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-868X","authenticated-orcid":false,"given":"Amira M.","family":"Badr","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, KSU  Riyadh Saudi Arabia"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maha A.","family":"AL\u2010Amin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, KSU  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6306-5616","authenticated-orcid":false,"given":"Yasmen F.","family":"Mahran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12922"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22484"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.10326"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.04169"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1318"},{"key":"e_1_2_10_7_1","volume":"7","author":"Li H.\u2010L.","year":"2017","journal-title":"Front. 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