{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:32:03Z","timestamp":1777667523122,"version":"3.51.4"},"reference-count":83,"publisher":"SAGE Publications","issue":"12_suppl","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>Hepatocellular carcinoma (HCC) accounts for more than 5% of all human cancers. Diacerein (DIA), an interleukin (IL)-1\u03b2 inhibitor, is used for the treatment of osteoarthritis. DIA is a potential anticancer drug acting on several protein targets in the process of apoptosis. The present study aimed to explore the molecular mechanisms underlying the effect of DIA in the treatment of trichloroacetic acid (TCA)\u2013induced pre-neoplastic changes in rats. Rats were allocated into 5 groups and treated for 4 weeks. Group 1: control; received vehicle, Group 2: TCA group; received TCA (1\u00a0g\/kg, orally for 5 days). Group 3: DIA-treated group; received TCA +DIA (50\u00a0mg\/kg\/day, orally, for 4 weeks). Group 4: positive control group; received TCA (1\u00a0g\/kg, orally, for 5 days) + 5-fluorouracil (5-FU) (75\u00a0mg\/kg) intraperitoneally (i.p.), for 4 weeks as a standard anticancer drug. Group 5: received TCA (1\u00a0g\/kg, orally for 5 days) + DIA (50\u00a0mg\/kg\/day, orally, for 4 weeks) + 5-FU (75\u00a0mg\/kg, i.p., for 4 weeks). Serum liver enzymes, oxidative stress parameters, inflammatory parameter (IL-1\u03b2), and angiogenesis marker vascular endothelial growth factor (VEGF) were assessed along with histopathological evaluation. An apoptotic marker as caspase-3 expression was measured by western blot analysis. Immunoexpression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) was evaluated. Results and conclusion: The outcomes proved that at histological level, DIA ameliorated hepatic precancerous lesion via modulation of IL-1\u03b2\u2013HIF-1\u03b1\u2013VEGF pathway.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>IL-1\u03b2 mediates angiogenesis indirectly, as it has been shown to induce hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) which upregulates VEGF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271211056331","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T06:35:24Z","timestamp":1641796524000},"page":"S788-S803","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid\u2013induced hepatic pre-neoplastic lesions in 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