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In the present study, the antibacterial, antibiofilm, toxicological, histopathological, and immunomodulatory effects of\n                    <jats:italic>Rhizophora apiculata<\/jats:italic>\n                    leaf extract were investigated against\n                    <jats:italic>Aeromonas hydrophila<\/jats:italic>\n                    using zebrafish (\n                    <jats:italic>Danio rerio<\/jats:italic>\n                    ) as a vertebrate model. The methanolic leaf extract was characterized by FTIR and GC\u2013MS analyses, which indicated the presence of diverse functional groups and putatively identified metabolites belonging to several chemical classes. The extract exhibited antibacterial activity against\n                    <jats:italic>A. hydrophila<\/jats:italic>\n                    , with a minimum inhibitory concentration (MIC) of 125\u2009\u03bcg\/mL, compared with 15.6\u2009\u03bcg\/mL for ampicillin. Quantitative crystal violet and confocal microscopy analyses demonstrated concentration\u2010 and time\u2010dependent inhibition and disruption of established biofilms, with the greatest effect observed at 500\u2009\u03bcg\/mL after 48\u2009h. Acute toxicity assessment revealed concentration\u2010dependent mortality, with 96\u2010h LC\n                    <jats:sub>50<\/jats:sub>\n                    values of 375\u2009\u03bcg\/mL for embryos and larvae and 200.5\u2009\u03bcg\/mL for adults, indicating greater sensitivity of adult fish. In\n                    <jats:italic>A. hydrophila<\/jats:italic>\n                    \u2010challenged zebrafish, treatment with the extract reduced infection\u2010associated gill and muscle alterations and improved the observed developmental morphology. The treatment was also associated with differential expression of\n                    <jats:italic>IL\u20108<\/jats:italic>\n                    ,\n                    <jats:italic>TNF\u2010\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>TGF\u2010\u03b2<\/jats:italic>\n                    , indicating modulation of immune\u2010related transcriptional responses. However, the treatment concentration of 250\u2009\u03bcg\/mL exceeded the estimated adult LC\n                    <jats:sub>50<\/jats:sub>\n                    , limiting interpretation of these protective responses as evidence of a safe therapeutic dose. Overall, the findings demonstrate antibacterial, antibiofilm, tissue\u2010protective, and transcriptional immunomodulatory activity of\n                    <jats:italic>R. apiculata<\/jats:italic>\n                    extract, while emphasizing the need for lower\u2010dose studies to establish a safer efficacy\u2013toxicity window for potential aquaculture applications.\n                  <\/jats:p>","DOI":"10.1002\/tox.70199","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:55:16Z","timestamp":1791345316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Toxicological and Immunological Evaluation of\n                    <scp>\n                      <i>Rhizophora apiculata<\/i>\n                    <\/scp>\n                    Leaf Extract Against\n                    <scp>\n                      <i>Aeromonas hydrophila<\/i>\n                    <\/scp>\n                    Infection in Zebrafish (\n                    <scp>\n                      <i>Danio rerio<\/i>\n                    <\/scp>\n                    )"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3031-8258","authenticated-orcid":false,"given":"Krishnamoorthy","family":"Santhosh","sequence":"first","affiliation":[{"name":"Centre for Marine and Aquatic Research (CMAR) Saveetha Institute of Medical and Technical Sciences, Saveetha University  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7032-1892","authenticated-orcid":false,"given":"Pitchiah","family":"Sivaperumal","sequence":"additional","affiliation":[{"name":"Centre for Marine and Aquatic Research (CMAR) Saveetha Institute of Medical and Technical Sciences, Saveetha University  Chennai Tamil Nadu India"},{"name":"Department of Marine Sciences, Saveetha Institute of Natural and Physical Sciences (SINAPS), Saveetha Institute of Medical and Technical Sciences Saveetha University  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10499\u2010026\u201002548\u20105"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.5004\/dwt.2023.30019"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/raq.70097"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201089465\u20104"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42770\u2010021\u201000624\u2010x"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microb.2024.100194"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms13122863"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.15698\/mic2023.11.807"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12275\u2010017\u20107274\u2010x"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11157\u2010024\u201009702\u20106"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo15040276"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13399\u2010023\u201004439\u20108"},{"key":"e_1_2_14_14_1","first-page":"1","volume-title":"Bioactive Compounds in Mangroves and Their Associates","author":"Valleti P. 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