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The aim of the present study is to evaluate the combined toxicity of a serotonin reuptake inhibitor (FLX) and Zn<jats:sup>2+<\/jats:sup> on a non-target aquatic model organism <jats:italic>Daphnia magna<\/jats:italic>. Animals were exposed to single and binary combinations of FLX (20.5 and 41\u00a0\u00b5g\/L for subchronic and 41 and 82\u00a0\u00b5g\/L for acute exposures) and Zn<jats:sup>2+<\/jats:sup> (40\u00a0\u00b5g\/L for subchronic and 80\u00a0\u00b5g\/L for acute exposures).\u00a0In vivo\u00a0experiments were done for 7\u00a0days subchronic and 48\u00a0h acute exposure, while subcellular supernatants of whole Daphnia lysate (WDL) were directly treated with the same concentrations used in the acute experiments. Morphological characteristics, Ca<jats:sup>2+<\/jats:sup>-ATPase, antioxidant enzyme activities, and lipid peroxidation were examined. There was antioxidant system suppression and Ca<jats:sup>2+<\/jats:sup>-ATPase inhibition despite the diverse response patterns due to duration, concentration, and toxicant type. After acute exposure, biomarkers showed a diminishing trend compared to subchronic exposure. According to integrated biomarker response index (IBR) analysis,\u00a0in vivo\u00a0Zn<jats:sup>2+<\/jats:sup> exposure was reasonably effective on the health of <jats:italic>D. magna<\/jats:italic>, whereas exposure of WDL to Zn<jats:sup>2+<\/jats:sup> had a lesser impact. FLX toxicity increased in a concentration-dependent manner, reversed by the combined exposure. We concluded that potential pro-oxidative and adverse Ca<jats:sup>2+<\/jats:sup>-ATPase effects of FLX and Zn<jats:sup>2+<\/jats:sup> in <jats:italic>D. magna<\/jats:italic> may also have harmful impact on ecosystem levels. Pharmaceutical exposure (FLX) should be considered along with their potential to interact with other toxicants in aquatic biota.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s11356-024-32846-5","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T18:02:15Z","timestamp":1711389735000},"page":"27988-28006","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Binary effects of fluoxetine and zinc on the biomarker responses of the non-target model organism Daphnia magna"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0530-3751","authenticated-orcid":false,"given":"G\u00fcl\u00fczar","family":"Atli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuf","family":"Sevgiler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"32846_CR1","doi-asserted-by":"publisher","unstructured":"ASTM (2002) Standard guide for conducting acute toxicity tests on test materials with fishes, macroinvertebrates, and amphibians. 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