{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:08:41Z","timestamp":1785413321694,"version":"3.56.0"},"reference-count":73,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Environmental and Toxicological Research"},{"name":"NIGMS-RISE R25","award":["GM061838"],"award-info":[{"award-number":["GM061838"]}]},{"name":"NIGMS-RISE R25","award":["U54 MD007600"],"award-info":[{"award-number":["U54 MD007600"]}]},{"name":"INBRE","award":["P20GM103475"],"award-info":[{"award-number":["P20GM103475"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>This study assesses the impact of sublethal levels of four marine toxins ciguatoxin (CTX-1), maitotoxin-2 (MTX-2), saxitoxin (STX) and brevetoxin-2 (BTX-2) on murine hepatic detoxification enzymes expressed in mouse liver. CTX-1, BTX-2, and STX altered hepatic detoxification responses, but their effects were generally more limited or temporally variable than those observed with MTX-2. CTX-1 produced time-dependent changes in cytochromes P450 (CYPs)-associated activities, BTX-2 induced early CYP1A2 and CYP3A11 responses followed by later suppression, and STX reduced CYP1A2 and CYP3A11 while increasing microsomal reductase activities. Of these toxins, MTX-2 exhibited the highest toxicity, notably decreasing key proteins such as CYPs, including CYP1A2 and CYP3A11. CYP enzymes are vital for metabolizing important endogenous and various xenobiotic substances, including therapeutic drugs. After MTX-2 exposure, both CYP1A2 and CYP3A11 levels dropped significantly at 12 h (p &lt; 0.0001 for CYP3A11, p &lt; 0.0001 for CYP1A2). Histopathological analysis revealed liver damage; however, albumin mRNA levels remained stable post-MTX-2 treatment, indicating that hepatotoxicity was not the sole cause of CYP3A11 reduction. Immunohistochemical analysis displayed uniform CYP3A11 distribution across liver regions after MTX-2 treatment. This suggests that MTX-2 exposure could augment the toxicity of drugs like Aldactone, Erythromycin, and Cyclosporine that utilize this metabolic pathway in humans. This is the first type of research performed of this nature, which could add to our understanding of marine toxin metabolism. These findings provide additional toxicological insights into the effects of four marine toxins on detoxification enzymes, with particular interest in MTX-2 toxicity, and potential implications for the treatment of fish poisoning, including ciguatera fish poisoning.<\/jats:p>","DOI":"10.3390\/toxins18080331","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:54Z","timestamp":1785411534000},"page":"331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Four Marine Toxins on Murine Hepatic Biotransformation Enzymes"],"prefix":"10.3390","volume":"18","author":[{"given":"Joanna","family":"Soto de Jesus","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gonz\u00e1lez-Keelan","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Mel\u00e9ndez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen L.","family":"Cadilla","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Contreras","sequence":"additional","affiliation":[{"name":"School of Medicine, Universidad Central del Caribe, Bayam\u00f3n, PR 00960, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7878-769X","authenticated-orcid":false,"given":"Braulio D.","family":"Jim\u00e9nez-V\u00e9lez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.hal.2008.08.006","article-title":"Eutrophication and Harmful Algal Blooms: A Scientific Consensus","volume":"8","author":"Heisler","year":"2008","journal-title":"Harmful Algae"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.3390\/toxins7041030","article-title":"Acute cardiotoxicity evaluation of the marine biotoxins OA, DTX-1 and YTX","volume":"7","author":"Ferreiro","year":"2015","journal-title":"Toxins"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.toxicon.2015.10.007","article-title":"Assessment of emerging biotoxins (pinnatoxin G and spirolides) at Europe\u2019s first marine reserve: Lough Hyne","volume":"108","author":"McCarthy","year":"2015","journal-title":"Toxicon"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101655","DOI":"10.1016\/j.hal.2019.101655","article-title":"Climate change and harmful benthic microalgae","volume":"91","author":"Tester","year":"2020","journal-title":"Harmful Algae"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Visciano, P., Schirone, M., Berti, M., Milandri, A., Tofalo, R., and Suzzi, G. 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