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Thymoquinone (TQ), the main bioactive constituent of <jats:italic>Nigella sativa<\/jats:italic>, exhibits anti\u2010inflammatory and antineoplastic activities against various cancers. Therefore, TQ was tested as an inhibitor of the initial phase of diethylnitrosamine (DEN)\u2010induced HCC in rats.\u00a0Twenty\u2010four male Wistar albino rats were randomly placed into four equal groups. Group 1 received saline and acted as the negative control; Group 2 received TQ; Group 3 received DEN; and Group 4 received TQ for 7 days and DEN on the 8th day. After 24\u2009h of fasting, blood samples were taken from the slaughtered rats. Additionally, each rat's liver was dissected and separated into two halves for histological and biochemical investigation.\u00a0DEN\u2010induced hepatotoxicity was detected by elevated hepatic enzymes and HCC biomarkers reduced antioxidant and proapoptotic statuses. DEN administration caused a significant increase in the levels of glutathione, superoxide dismutase, malondialdehyde, caspase\u20103, alpha\u2010fetoprotein (AFP), AFPL3, glypican 3, and the expression of BAX. However, DEN significantly decreased glutathione peroxidase, catalase, and CYP2E1 and the expression of BCl\u20102. Furthermore, it caused histological changes and showed a strong positive GSH <jats:italic>S<\/jats:italic>\u2010transferase P expression in the hepatic parenchyma. Pretreatment with TQ prevented the histopathological and most of the biochemical changes and improved the antioxidant status.\u00a0TQ supplementation appears to suppress the development of DEN\u2010initiated liver cancer by reducing oxidative stress, activating the intrinsic mitotic apoptosis pathway, and retaining the antioxidant enzymes.<\/jats:p>","DOI":"10.1002\/jbt.23078","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T08:06:04Z","timestamp":1650355564000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Suppressive effects of thymoquinone on the initiation stage of diethylnitrosamine hepatocarcinogenesis in rats"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-9310","authenticated-orcid":false,"given":"Samar","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Clinical Pharmacy Practice Department, Faculty of Pharmacy Ahram Canadian University 6th of October City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally A.","family":"Fahim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Pharmacy Newgiza University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer A.","family":"Tadros","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy October University for Modern Sciences and Arts (MSA)  6th of October City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama A.","family":"Badary","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Practice Department, Faculty of Pharmacy The British University in Egypt (BUE) Cairo Egypt"},{"name":"Clinical Pharmacy Department, Faculty of Pharmacy Ain Shams University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.07.060"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.3055"},{"key":"e_1_2_7_5_1","first-page":"3697","volume":"17","author":"Intaraprasong P.","year":"2016","journal-title":"Asian Pac. 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