{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:07:58Z","timestamp":1792552078734,"version":"4.5.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Egyptian Atomic Energy Authority"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genes Nutr"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diethylnitrosamine (DEN) induces hepatic injury and can promote hepatocarcinogenesis. Quercetin (QR) and low-dose gamma irradiation (LDR) have been explored as hepatoprotective and anticancer-modulating agents, but their combined effects in DEN-induced liver cancer have not been previously examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To, for the first time, evaluate the novel combination of QR with LDR and compare its efficacy to QR or LDR alone in modulating DEN-induced liver cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hepatic injury was induced in ninety male rats by intraperitoneal DEN administration (75\u00a0mg\/kg weekly for 3 weeks, then 100\u00a0mg\/kg weekly for 3 weeks). After 6 weeks, hepatic injury establishment was confirmed histopathologically in a subset of rats. Animals were then randomized into five groups for an 8-week treatment period: (C) normal control; (DEN) no further treatment; (DEN\u2009+\u2009QR) quercetin (50\u00a0mg\/kg\/day, oral); (DEN\u2009+\u2009IR) fractionated low-dose \u03b3-irradiation (0.25\u00a0Gy once weekly for 4 weeks, total 1\u00a0Gy); (DEN\u2009+\u2009QR+IR) combined QR\u2009+\u2009IR. The total experimental duration was 14 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DEN induced severe hepatotoxicity, with significantly elevated serum ALT and AST compared to controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Markers of oxidative stress were markedly increased, while antioxidant enzymes and GSH were significantly reduced (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). DEN also led to substantial activation of inflammatory and growth signaling pathways, including NF-\u03baB, STAT-3, mTOR, and p38 MAPK (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Autophagy markers ULK-1, LC3-II, and ATG5 were significantly suppressed, and a pro-survival shift was evident with reduced caspase-3 activity and increased BCL-2 expression (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).Treatment with quercetin (DEN\u2009+\u2009QR) or low-dose \u03b3-irradiation (DEN\u2009+\u2009IR) alone significantly mitigated these alterations versus DEN, restoring liver enzymes, reducing oxidative stress and inflammation, and promoting apoptotic signaling (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The combination therapy (DEN\u2009+\u2009QR+IR) produced the most pronounced effects, with greater normalization of all biochemical and molecular parameters compared to DEN and to either monotherapy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). These changes were statistically superior to those observed with quercetin or irradiation alone (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Flow cytometry confirmed enhanced apoptosis and altered cell cycle dynamics in the combination group. Histopathological analysis showed markedly improved hepatic architecture and the lowest pathology scores with combination therapy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 vs. DEN).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals, for the first time, a combined hepatoprotective effect of quercetin with low-dose gamma irradiation in DEN-induced liver pathology, suggesting new mechanistic insights and promising translational potential for combined therapy in DEN-associated liver injury and hepatocarcinogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial<\/jats:title>\n                    <jats:p>This work isn\u2019t a clinical Trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12263-026-00810-2","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:50:54Z","timestamp":1781769054000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quercetin and low-dose gamma irradiation modulate oxidative stress, inflammation, autophagy, and apoptosis in DEN-induced hepatocarcinogenesis"],"prefix":"10.1186","volume":"21","author":[{"given":"Nayera S.","family":"Khatab","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nermeen M.","family":"Elbakary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rokaya E.","family":"Maarouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faten","family":"Zahran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"issue":"7","key":"810_CR1","first-page":"207","volume":"13","author":"N Amin","year":"2025","unstructured":"Amin N, Anwar J, Sulaiman A, Naumova NN, Anwar N. 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