{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:05:06Z","timestamp":1787166306335,"version":"build-2736575974"},"reference-count":172,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Research, Innovation and Digitization","award":["PN-III-P4-PCE-2021-0639"],"award-info":[{"award-number":["PN-III-P4-PCE-2021-0639"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Environmental concerns have consistently been a focal point for the scientific community. Pollution is a critical ecological issue that poses significant threats to human health and agricultural production. Contamination with heavy metals and pesticides is a considerable concern, a threat to the environment, and warrants special attention. In this study, we investigated the significant issues arising from sub-chronic exposure to imidacloprid (IMI), mercury (Hg), and cadmium (Cd), either alone or in combination, using zebrafish (Danio rerio) as an animal model. Additionally, we assessed the potential protective effects of polyfloral honey enriched with natural ingredients, also called honey formulation (HF), against the combined sub-chronic toxic effects of the three contaminants. The effects of IMI (0.5 mg\u00b7L\u22121), Hg (15 \u03bcg\u00b7L\u22121), and Cd (5 \u03bcg\u00b7L\u22121), both individually and in combination with HF (500 mg\u00b7L\u22121), on zebrafish were evaluated by quantifying acetylcholinesterase (AChE) activity, lipid peroxidation (MDA), various antioxidant enzyme activities like superoxide dismutase and glutathione peroxidase (SOD and GPx), 2D locomotor activity, social behavior, histological and immunohistochemical factors, and changes in body element concentrations. Our findings revealed that all concentrations of pollutants may disrupt social behavior, diminish swimming performances (measured by total distance traveled, inactivity, and swimming speed), and elevate oxidative stress (OS) biomarkers of SOD, GPx, and MDA in zebrafish over the 21-day administration period. Fish exposed to IMI and Hg + Cd + IMI displayed severe lesions and increased GFAP (Glial fibrillary acidic protein) and S100B (S100 calcium-binding protein B) protein expression in the optic tectum and cerebellum, conclusively indicating astrocyte activation and neurotoxic effects. Furthermore, PCNA (Proliferating cell nuclear antigen) staining revealed reduced cell proliferation in the IMI-exposed group, contrasting with intensified proliferation in the Hg + Cd group. The nervous system exhibited significant damage across all studied concentrations, confirming the observed behavioral changes. Moreover, HF supplementation significantly mitigated the toxicity induced by contaminants and reduced OS. Therefore, the exposure to chemical mixtures offers a more complete picture of adverse impacts on aquatic ecosystems and the supplementation with bioactive compounds can help to reduce the toxicity induced by exposure to environmental pollutants.<\/jats:p>","DOI":"10.3390\/ijms252111730","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T12:31:32Z","timestamp":1730377892000},"page":"11730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Honey Enriched with Additives Alleviates Behavioral, Oxidative Stress, and Brain Alterations Induced by Heavy Metals and Imidacloprid in Zebrafish"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-5174","authenticated-orcid":false,"given":"Emanuela","family":"Paduraru","sequence":"first","affiliation":[{"name":"Doctoral School of Geosciences, Faculty of Geography and Geology, Alexandru Ioan Cuza University of Iasi, No. 20 A Carol I Avenue, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0354-943X","authenticated-orcid":false,"given":"Roxana","family":"Jijie","sequence":"additional","affiliation":[{"name":"Research Center on Advanced Materials and Technologies (RAMTECH), Department of Exact and Natural Sciences, Institute of Interdisciplinary Research, Alexandru Ioan Cuza University of Iasi, No. 11 Carol I Avenue, 700506 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira-Adeline","family":"Simionov","sequence":"additional","affiliation":[{"name":"Department of Food Science, Food Engineering, Biotechnologies and Aquaculture, Dunarea de Jos University of Galati, No. 47 Domneasc\u0103 Street, 800008 Galati, Romania"},{"name":"REXDAN Research Infrastructure, Dunarea de Jos University of Galati, No. 98 George Co\u0219buc Street, 800385 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina-Maria","family":"Gavrilescu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Grigore T. Popa University of Medicine and Pharmacy, No. 16 University Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tudor","family":"Ilie","sequence":"additional","affiliation":[{"name":"Synergy Plant Products, No. 12 Milano Street, Prejmer, 507165 Brasov, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3321-3398","authenticated-orcid":false,"given":"Diana","family":"Iacob","sequence":"additional","affiliation":[{"name":"Doctoral School of Geosciences, Faculty of Geography and Geology, Alexandru Ioan Cuza University of Iasi, No. 20 A Carol I Avenue, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2484-055X","authenticated-orcid":false,"given":"Andreea","family":"Lupitu","sequence":"additional","affiliation":[{"name":"Faculty of Food Engineering, Tourism and Environmental Protection, Institute for Research, Development and Innovation in Technical and Natural Sciences, Aurel Vlaicu University, No. 2 Elena Dragoi Street, 310330 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8487-4984","authenticated-orcid":false,"given":"Cristian","family":"Moisa","sequence":"additional","affiliation":[{"name":"Faculty of Food Engineering, Tourism and Environmental Protection, Institute for Research, Development and Innovation in Technical and Natural Sciences, Aurel Vlaicu University, No. 2 Elena Dragoi Street, 310330 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7512-2422","authenticated-orcid":false,"given":"Claudia","family":"Muresan","sequence":"additional","affiliation":[{"name":"Faculty of Food Engineering, Tourism and Environmental Protection, Institute for Research, Development and Innovation in Technical and Natural Sciences, Aurel Vlaicu University, No. 2 Elena Dragoi Street, 310330 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-200X","authenticated-orcid":false,"given":"Lucian","family":"Copolovici","sequence":"additional","affiliation":[{"name":"Faculty of Food Engineering, Tourism and Environmental Protection, Institute for Research, Development and Innovation in Technical and Natural Sciences, Aurel Vlaicu University, No. 2 Elena Dragoi Street, 310330 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-0473","authenticated-orcid":false,"given":"Dana M.","family":"Copolovici","sequence":"additional","affiliation":[{"name":"Faculty of Food Engineering, Tourism and Environmental Protection, Institute for Research, Development and Innovation in Technical and Natural Sciences, Aurel Vlaicu University, No. 2 Elena Dragoi Street, 310330 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Mihalache","sequence":"additional","affiliation":[{"name":"Integrated Center of Environmental Science Studies in the North-Eastern Development Region (CERNESIM), Department of Exact and Natural Sciences, Institute of Interdisciplinary Research, Alexandru Ioan Cuza University of Iasi, No. 11 Carol I Avenue, 700506 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2127-4225","authenticated-orcid":false,"given":"Florin Daniel","family":"Lipsa","sequence":"additional","affiliation":[{"name":"Department of Food Technologies, Ion Ionescu de la Brad University of Life Sciences, No. 3 Mihail Sadoveanu Alley, 700490 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3067-9574","authenticated-orcid":false,"given":"Gheorghe","family":"Solcan","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Ion Ionescu de la Brad University of Life Sciences, No. 8 Mihail Sadoveanu Alley, 700489 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela-Alexandra","family":"Danelet","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Ion Ionescu de la Brad University of Life Sciences, No. 8 Mihail Sadoveanu Alley, 700489 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, Alexandru Ioan Cuza University of Iasi, No. 20 A Carol I Avenue, 700505 Iasi, Romania"},{"name":"Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, No. 20A Carol I Avenue, 700505 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alin","family":"Ciobica","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, No. 20A Carol I Avenue, 700505 Iasi, Romania"},{"name":"Center of Biomedical Research, Romanian Academy, No. 8 Carol I Avenue, 700506 Iasi, Romania"},{"name":"Academy of Romanian Scientists, No. 54 Independence Street, Sector 5, 050094 Bucharest, Romania"},{"name":"\u201cIoan Haulica\u201d Institute, Apollonia University, No. 11 Pacurari Street, 700511 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-0296","authenticated-orcid":false,"given":"Carmen","family":"Solcan","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Ion Ionescu de la Brad University of Life Sciences, No. 8 Mihail Sadoveanu Alley, 700489 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tomczyk, M., Mi\u0142ek, M., Sidor, E., Kapusta, I., Litwi\u0144czuk, W., Puchalski, C., and D\u017cugan, M. 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