{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:56:23Z","timestamp":1791669383023,"version":"4.3.4"},"reference-count":83,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Fish Biology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Elevated water hardness (HW) level could negatively impact the health of various kinds of fish, especially Nile tilapia. The current work aimed to explore the cytoprotective role of rutin (RUT), a natural antioxidant, against HW\u2010induced cell injury in Nile tilapia, and to find the possible mechanistic pathways underlying this protection. Sixty monosex fish were allocated into four different experimental groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915): control, RUT (1\u2009g\/kg), HW\u2010exposed group (300\u2009ppm) and HW\u2009+\u2009RUT group. The daily exposure of fish to elevated HW for 90\u2009days significantly altered the haematological profile, increased malondialdehyde (MDA) and nitric oxide (NO) levels and reduced the antioxidant enzyme activity. Additionally, it elevated the serum levels of both liver and kidney function biomarkers, alongside pronounced histopathological alterations in gills, the liver and kidneys. Mechanistically, the HW markedly increased the expression of either gene or protein levels of iNOS, casp\u20103,\n                    <jats:italic>CYP1A1<\/jats:italic>\n                    ,\n                    <jats:italic>MT\u20101<\/jats:italic>\n                    and\n                    <jats:italic>Hsp70<\/jats:italic>\n                    in both the liver and kidneys, alongside strong proliferating cell nuclear antigen (PCNA) immunoexpression in the gills. In contrast, dietary RUT effectively ameliorated the toxicological alterations induced by elevated HW, contributing to the enhancement of immune and antioxidant defence mechanisms, which therefore reduced the aforementioned cell signalling pathways. In conclusion, the potent antioxidant, anti\u2010apoptotic and immunostimulant properties of RUT can contribute to reducing HW\u2010induced toxicity in Nile tilapia.\n                  <\/jats:p>","DOI":"10.1111\/jfb.70457","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:44:52Z","timestamp":1776818692000},"page":"743-760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pathological, immunohistochemical and molecular studies on rutin's protective effects against water hardness\u2010induced cytotoxicity in Nile tilapia,\n                    <scp>\n                      <i>Oreochromis niloticus<\/i>\n                    <\/scp>"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-2114","authenticated-orcid":false,"given":"Wafaa A.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine Cairo University  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3670-6841","authenticated-orcid":false,"given":"Eman I.","family":"Hassanen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine Cairo University  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1261-9313","authenticated-orcid":false,"given":"Hanan S.","family":"Khalefa","sequence":"additional","affiliation":[{"name":"Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine Cairo University  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-4289","authenticated-orcid":false,"given":"Neven H.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Veterinary Medicine Cairo University  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7935-8379","authenticated-orcid":false,"given":"Marwa A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine Cairo University  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9385-2549","authenticated-orcid":false,"given":"Mahmoud A.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine Cairo University  Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2017.1387575"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/anu.13361"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-024-04199-0"},{"issue":"2","key":"e_1_2_10_5_1","first-page":"1207","article-title":"Restoration of heavy metals accumulation and hemato\u2010biochemical markers in puntins ticto fish with administration of ziziphus oxyphylla edgew extract","volume":"19","author":"Ahmad B.","year":"2023","journal-title":"Journal of Xi'an Shiyou University (Natural Science Edition)"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquaculture.2022.737934"},{"issue":"8","key":"e_1_2_10_7_1","first-page":"3800","article-title":"Comparative efficacy of anesthetic agents (clove oil and sodium bicarbonate) on cultured African catfish, Clarias gariepinus (Burchell, 1822) and Nile tilapia, Oreochromis niloticus (Linnaeus, 1758)","volume":"7","author":"Akinjogunla V. 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