{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:11:07Z","timestamp":1791540667510,"version":"4.3.4"},"reference-count":98,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Pharmaceutical compounds frequently co-occur in environmental waters, but studies on their combined effects on animals and humans remain limited. The present study investigated the individual and combined short-term effects of ketoprofen (Kp, a nonsteroidal anti-inflammatory drug inhibiting cyclooxygenase-2), valproic acid (VPA, an anticonvulsant acting as a voltage-gated sodium channel modulator), and meropenem (Mp, a \u03b2-lactam antibiotic) at environmentally relevant concentrations on zebrafish behavior, acetylcholinesterase (AChE) activity, and oxidative status. Methods: Adult zebrafish were exposed for 4 days to Kp, VPA, Mp, and their binary and ternary mixtures. Behavioral effects were assessed using 3D novel tank and social behavior tests, while the oxidative stress response was assessed through malondialdehyde (MDA) content, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Results: Zebrafish exposed to Mp showed a notable increase in immobility, whereas those exposed to VPA and Mp + Kp exhibited a significant augmentation of average velocity and counter-clockwise rotations. All treated groups exhibited a notable increase in the time spent near the walls (thigmotaxis), and except for the control and Mp-exposed zebrafish, the other groups mostly stayed in the bottom tank zone (geotaxis). Kp, VPA + Kp, and VPA + Mp + Kp treatments impaired social behavior, with zebrafish displaying less interest in conspecifics. Biochemical analysis demonstrated that both the individual drugs and their combination caused oxidative stress, characterized by decreased GPx activity and increased SOD activity and MDA levels. Moreover, AChE activity was more strongly inhibited in zebrafish exposed to the binary and ternary mixtures than to individual drugs. Conclusions: The results indicate that acute exposure to individual and\/or combined pharmaceuticals induces behavioral changes, oxidative damage, and AChE inhibition in zebrafish, highlighting the need to assess the effects of pharmaceutical mixtures for comprehensive ecosystem risks evaluation.<\/jats:p>","DOI":"10.3390\/ph18081096","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T07:54:26Z","timestamp":1753343666000},"page":"1096","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Single and Combined Effects of Meropenem, Valproic Acid, and Ketoprofen on Adult Zebrafish Behavior, Oxidative Stress, and Acetylcholinesterase Activity"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0383-1799","authenticated-orcid":false,"given":"Ionut-Alexandru","family":"Chelaru","sequence":"first","affiliation":[{"name":"Doctoral School of Geosciences, Faculty of Geography and Geology, \u201cAlexandru Ioan Cuza\u201d University of Iasi, Bd. Carol I, 700505 Iasi, Romania"},{"name":"Department of Biology, Faculty of Sciences, \u201cVasile Alecsandri\u201d University of Bacau, Marasesti Street, 600115 Bacau, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0354-943X","authenticated-orcid":false,"given":"Roxana","family":"Strungaru-Jijie","sequence":"additional","affiliation":[{"name":"Research Center Advanced Materials and Technologies (RAMTECH), Department of Exact and Natural Sciences, Institute of Interdisciplinary Research, \u201cAlexandru Ioan Cuza\u201d University of Iasi, Bd. Carol I, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9755-6771","authenticated-orcid":false,"given":"Mircea","family":"Nicoara","sequence":"additional","affiliation":[{"name":"Doctoral School of Geosciences, Faculty of Geography and Geology, \u201cAlexandru Ioan Cuza\u201d University of Iasi, Bd. Carol I, 700505 Iasi, Romania"},{"name":"Department of Biology, Faculty of Biology, \u201cAlexandru Ioan Cuza\u201d University of Iasi, Bd. Carol I, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0922-740X","authenticated-orcid":false,"given":"Diana","family":"Mirila","sequence":"additional","affiliation":[{"name":"Department of Environmental Engineering, Mechanical Engineering and Agritourism, Faculty of Engineering, \u201cVasile Alecsandri\u201d University of Bacau, Marasesti Street, 600115 Bacau, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alin","family":"Ciobica","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Biology, \u201cAlexandru Ioan Cuza\u201d University of Iasi, Bd. Carol I, 700505 Iasi, Romania"},{"name":"\u201cIoan Haulica\u201d Institute, Apollonia University, Pacurari Street 11, 700511 Iasi, Romania"},{"name":"\u201cOlga Necrasov\u201d Center, Department of Biomedical Research, Romanian Academy, 010071 Iasi, Romania"},{"name":"Multidisciplinary Medical Research and Development Platform in the North-East Region (CENEMED), \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorel","family":"Ureche","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences, \u201cVasile Alecsandri\u201d University of Bacau, Marasesti Street, 600115 Bacau, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114993","DOI":"10.1016\/j.envpol.2020.114993","article-title":"Evaluation of ketoprofen toxicity in two freshwater species: Effects on biochemical, physiological and population endpoints","volume":"265","author":"Alkimin","year":"2020","journal-title":"Environ. 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