{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:18:50Z","timestamp":1787980730666,"version":"build-2784847793"},"reference-count":87,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Xenobiotics","JoX"],"abstract":"<jats:p>Chemical pollution from industrial, agricultural, and urban activities represents a major threat to freshwater ecosystems and aquatic organisms. This study evaluated hepatic biomarker responses in Oreochromis niloticus (Nile tilapia) maintained under chronic environmental exposure to water from the Igua\u00e7u River, one of the most polluted urban rivers in Brazil. Juvenile fish were kept in cages at three sites along the river, and hepatic biomarkers were assessed after 15 and 22 months of environmental exposure. Fish showed severe histopathological liver lesions, activation of antioxidant defenses, and oxidative stress responses accompanied by increased DNA damage. Immunological responses, particularly melanomacrophage proliferation and granuloma formation, were also observed across the monitored exposure scenarios. Alterations in plasma biochemical parameters, including AST, ALT, LDH, albumin, and globulin, were consistent with changes in hepatic function. Overall, the integrated biomarker responses revealed distinct patterns of biological alteration among the monitored exposure scenarios and were consistent with chronic exposure to complex environmental contaminant mixtures. These findings are consistent with alterations in liver integrity in fish maintained under long-term environmental exposure in the Igua\u00e7u River. The study highlights the sensitivity of Nile tilapia as a bioindicator species for aquatic biomonitoring and provides valuable information to support environmental monitoring, risk assessment, and conservation strategies for the Igua\u00e7u River Basin.<\/jats:p>","DOI":"10.3390\/jox16050162","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:58:21Z","timestamp":1787828301000},"page":"162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Monitoring Hepatic Biomarker Responses in Caged Oreochromis niloticus Under Chronic Exposure to Micropollutants in the Igua\u00e7u River"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1702-2284","authenticated-orcid":false,"given":"Lorena","family":"Bavia","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paran\u00e1, Curitiba CEP 81531-970, PR, Brazil"},{"name":"Faculdades Pequeno Pr\u00edncipe, Av. Igua\u00e7u, 333, Rebou\u00e7as, Curitiba CEP 80230-020, PR, Brazil"},{"name":"Instituto de Pesquisa Pel\u00e9 Pequeno Pr\u00edncipe, Av. Silva Jardim, 1632, \u00c1gua Verde, Curitiba CEP 80250-060, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2490-9769","authenticated-orcid":false,"given":"Rayanne Seibel","family":"Littig","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paran\u00e1, Curitiba CEP 81531-970, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-595X","authenticated-orcid":false,"given":"Manuela Santos","family":"Santana","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paran\u00e1, Curitiba CEP 81531-970, PR, Brazil"},{"name":"Laborat\u00f3rio de Ecologia Marinha, Centro de Estudos do Mar, Universidade Federal do Paran\u00e1, Pontal do Paran\u00e1 CEP 83255-000, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1077-1506","authenticated-orcid":false,"given":"Milena Carvalho","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo CEP 05508-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza Santos","family":"Barreto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paran\u00e1, Curitiba CEP 81531-970, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-5252","authenticated-orcid":false,"given":"Tha\u00eds Muniz","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Faculdades Pequeno Pr\u00edncipe, Av. 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Silva Jardim, 1632, \u00c1gua Verde, Curitiba CEP 80250-060, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-6843","authenticated-orcid":false,"given":"Marco Antonio Ferreira","family":"Randi","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paran\u00e1, Curitiba CEP 81531-970, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2515-5565","authenticated-orcid":false,"given":"Cesar Castro","family":"Martins","sequence":"additional","affiliation":[{"name":"Instituto Oceanogr\u00e1fico, Universidade de S\u00e3o Paulo, S\u00e3o Paulo CEP 05508-120, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4381-9908","authenticated-orcid":false,"given":"Andrea Pinto","family":"De Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidade Federal do Paran\u00e1, Curitiba CEP 81531-980, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iracema","family":"Opuskevitch","sequence":"additional","affiliation":[{"name":"Copel GeT-SOS\/DNGT, Jos\u00e9 Izidoro Biazetto, 185, Bloco a, Curitiba CEP 81200-240, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Cesar Alves","family":"Da Silva Ferreira","sequence":"additional","affiliation":[{"name":"Copel GeT-SOS\/DNGT, Jos\u00e9 Izidoro Biazetto, 185, Bloco a, Curitiba CEP 81200-240, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Esquivel-Muelbert","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3168-9272","authenticated-orcid":false,"given":"Ciro Alberto","family":"De Oliveira Ribeiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paran\u00e1, Curitiba CEP 81531-970, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6950-9900","authenticated-orcid":false,"given":"Maritana Mela","family":"Prodocimo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paran\u00e1, Curitiba CEP 81531-970, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ecoenv.2017.11.036","article-title":"Diffuse sources of contamination in freshwater fish: Detecting effects through active biomonitoring and multi-biomarker approaches","volume":"149","author":"Santana","year":"2018","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119360","DOI":"10.1016\/j.marpolbul.2026.119360","article-title":"Microplastic contamination in thirty commercially important fish species: Distribution, polymer composition, pollution indices, and human health risks","volume":"226","author":"Arivukumar","year":"2026","journal-title":"Mar. Pollut. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103682","DOI":"10.1016\/j.etap.2021.103682","article-title":"Exposure to pollutants present in Igua\u00e7u River Southern Brazil affect the health of Oreochromis niloticus (Linnaeus, 1758): Assessment histological, genotoxic and biochemical","volume":"87","author":"Neto","year":"2021","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"140812","DOI":"10.1016\/j.chemosphere.2023.140812","article-title":"Pollutant bioaccumulation in sentinel fish chronically exposed in Igua\u00e7u river reservoirs (Southern Brazil) and human health risk of fish consumption","volume":"349","author":"Randi","year":"2024","journal-title":"Chemosphere"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Santos, S.W., Cachot, J., Cormier, B., Mazzella, N., Gourves, P.Y., Cl\u00e9randeau, C., Morin, B., and Gonzalez, P. (2021). Environmentally relevant mixture of pesticides affect mobility and DNA integrity of early life stages of rainbow trout (Oncorhynchus mykiss). Toxics, 9.","DOI":"10.3390\/toxics9080174"},{"key":"ref_6","unstructured":"United Nations (2021). The United Nations World Water Development Report 2021: Valuing Water, UNESCO. Available online: https:\/\/unesdoc.unesco.org\/ark:\/48223\/pf0000375724."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kumar, A., Thakur, C., Thakur, K., Sharma, A.K., Daroch, R.K., Kumar, R., Kumar, S., and Sharma, A.K. (2026). A Systematic Review on Classification, Exposure Pathways of Micropollutants in the Aquatic Environment, and Its Associated Human Health Risks. J. Appl. Toxicol., 1\u201344.","DOI":"10.1002\/jat.70246"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0160-4120(03)00059-X","article-title":"Pollution correlated modifications of liver antioxidant systems and histopathology of fish (Cyprinidae) living in Seyhan Dam Lake, Turkey","volume":"30","author":"Doran","year":"2004","journal-title":"Environ. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1021\/acs.est.1c07176","article-title":"Effect of enterohepatic circulation on the accumulation of per- and polyfluoroalkyl substances: Evidence from experimental and computational studies","volume":"56","author":"Cao","year":"2022","journal-title":"Environ. Sci. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"128300","DOI":"10.1016\/j.envpol.2026.128300","article-title":"Chemical pollution alters detoxification capacity and behavior in the native freshwater fish Galaxias maculatus under in situ exposure","volume":"401","author":"Habit","year":"2026","journal-title":"Environ. Pollut."},{"key":"ref_11","first-page":"26","article-title":"Assessment of organochlorine pesticide residue levels and fat content in liver, gill and muscle tissues of catfish (Clarias spp.) and tilapia (Oreochromis spp.) obtained from River Kaduna and fish farms in Kaduna metropolis, Nigeria","volume":"15","author":"Akor","year":"2021","journal-title":"IOSR J. Environ. Sci. Toxicol. Food Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S1382-6689(02)00126-6","article-title":"Fish bioaccumulation and biomarkers in environmental risk assessment: A review","volume":"13","author":"Beyer","year":"2003","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18111","DOI":"10.1007\/s11356-016-6924-6","article-title":"Bioavailability of pollutants sets risk of exposure to biota and human population in reservoirs from Igua\u00e7u River (Southern Brazil)","volume":"23","author":"Yamamoto","year":"2016","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"48739","DOI":"10.1007\/s11356-023-26187-y","article-title":"Fish liver damage related to wastewater treatment plant effluents","volume":"30","author":"Popovic","year":"2023","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109673","DOI":"10.1016\/j.ecoenv.2019.109673","article-title":"Seasonal variations in the dose-response relationship of acetylcholinesterase activity in freshwater fish exposed to chlorpyrifos and glyphosate","volume":"187","author":"Cantera","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1111\/faf.12228","article-title":"Neotropical freshwater fishes imperilled by unsustainable policies","volume":"18","author":"Pelicice","year":"2017","journal-title":"Fish. Fish."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103596","DOI":"10.1016\/j.etap.2021.103596","article-title":"Micropollutants impair the survival of Oreochromis niloticus and threaten local species from Igua\u00e7u River, Southern Brazil","volume":"83","author":"Gemusse","year":"2021","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_18","first-page":"167","article-title":"Monitoring water quality in reservoirs for human supply through multi-biomarker evaluation in tropical fish","volume":"14","author":"Yamamoto","year":"2012","journal-title":"J. Environ. Monit."},{"key":"ref_19","unstructured":"(2025, December 16). IBGE\u2014Brazilian Institute of Geography and Statistics. Home Page, Available online: https:\/\/www.ibge.gov.br."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.envpol.2018.04.019","article-title":"Alterations of cytochrome P450 and the occurrence of persistent organic pollutants in tilapia caged in the reservoirs of the Igua\u00e7u River","volume":"240","author":"Yamamoto","year":"2018","journal-title":"Environ. Pollut."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3897\/zookeys.1041.63884","article-title":"Ichthyofauna in the Last Free-Flowing River of the Lower Igua\u00e7u Basin: Endemic Species","volume":"1041","author":"Pini","year":"2021","journal-title":"ZooKeys"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"134989","DOI":"10.1016\/j.chemosphere.2022.134989","article-title":"Organic and inorganic pollutants in Jord\u00e3o and Igua\u00e7u rivers, southern Brazil, impact early phases of Rhamdia quelen and represent a risk for population","volume":"303","author":"Golin","year":"2022","journal-title":"Chemosphere"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/j.scitotenv.2019.07.187","article-title":"Biochemical and histological alterations in Aequidens metae (Pisces, Cichlidae) and Astyanax gr. bimaculatus (Pisces, Characidae) as indicators of river pollution","volume":"692","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"124661","DOI":"10.1016\/j.envpol.2024.124661","article-title":"A critical review of pollution active biomonitoring using sentinel fish: Challenges and opportunities","volume":"360","author":"Bancel","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1039\/b608862g","article-title":"The effect of different holding conditions for environmental monitoring with caged rainbow trout (Oncorhynchus mykiss)","volume":"8","author":"Hanson","year":"2006","journal-title":"J. Environ. Monit."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.aquatox.2006.03.010","article-title":"Caging techniques for field exposures of fish to chemical contaminants","volume":"78","author":"Oikari","year":"2006","journal-title":"Aquat. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104034","DOI":"10.1016\/j.etap.2022.104034","article-title":"BDE-99 (2,2\u2032,4,4\u2032,5-pentain polybrominated diphenyl ether) induces toxic effects in Oreochromis niloticus after sub-chronic and oral exposure","volume":"97","author":"Brito","year":"2023","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"143193","DOI":"10.1016\/j.chemosphere.2024.143193","article-title":"Effects of inorganic and organic pollution on development of Steindachneridion melanodermatum from the Igua\u00e7u River, Brazil","volume":"364","author":"Barreto","year":"2024","journal-title":"Chemosphere"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1439-0426.2006.00805.x","article-title":"Cube law, condition factor and weight\u2013length relationships: History, meta-analysis and recommendations","volume":"22","author":"Froese","year":"2006","journal-title":"J. Appl. Ichthyol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.ecoenv.2017.08.009","article-title":"Implications of biological factors on accumulation of persistent organic pollutants in Antarctic notothenioid fish","volume":"145","author":"Lana","year":"2017","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109907","DOI":"10.1016\/j.ecoenv.2019.109907","article-title":"Urban effluents affect the early development stages of Brazilian fish species with implications for their population dynamics","volume":"188","author":"Barreto","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1016\/j.marpolbul.2006.09.011","article-title":"Assessment of contamination by polychlorinated biphenyls and aliphatic and aromatic hydrocarbons in sediments of the Santos and S\u00e3o Vicente Estuary System, S\u00e3o Paulo, Brazil","volume":"52","author":"Taniguchi","year":"2006","journal-title":"Mar. Pollut. Bull."},{"key":"ref_33","unstructured":"MacLeod, W., Brown, D., Friedman, A., Burrows, D., Maynes, O., Pearce, R., Wigren, C., and Bogar, R. (1985). Standard Analytical Procedures of the NOAA National Analytical Facility, 1985\u20131986, NOAA National Analytical Facility. U.S. Department of Commerce, NOAA Technical Memo NMFS F\/NWC-92."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein\u2013dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"Catalase in vitro","volume":"Volume 105","author":"Aebi","year":"1984","journal-title":"Methods in Enzymology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0003-9861(78)90479-4","article-title":"Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase","volume":"186","author":"Kono","year":"1978","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1016\/S0021-9258(20)81842-0","article-title":"Mechanism for the several activities of the glutathione S-transferases","volume":"251","author":"Keen","year":"1976","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/0003-2697(92)90122-N","article-title":"Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low-density lipoprotein","volume":"202","author":"Jiang","year":"1992","journal-title":"Anal. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"Anal. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"200168","DOI":"10.1016\/j.cirep.2024.200168","article-title":"Health status biomarkers and hemato-biochemical indices in Nile tilapia","volume":"7","author":"Bavia","year":"2024","journal-title":"Comp. Immunol. Rep."},{"key":"ref_41","unstructured":"Burtis, C.A., and Bruns, D.E. (2016). Tietz: Fundamentos de Qu\u00edmica Cl\u00ednica e Diagn\u00f3stico Molecular, Elsevier. [7th ed.]."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1046\/j.1365-2761.1999.00134.x","article-title":"Histopathology in fish: Proposal for a protocol to assess aquatic pollution","volume":"22","author":"Bernet","year":"1999","journal-title":"J. Fish. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ecoenv.2004.03.002","article-title":"Effects of dietary Pb(II) and tributyltin on neotropical fish, Hoplias malabaricus: Histopathological and biochemical findings","volume":"60","author":"Rabitto","year":"2005","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/tox.2530100309","article-title":"Evaluation of the genotoxicity of environmental contaminants in sediments to rainbow trout hepatocytes","volume":"10","author":"Blaise","year":"1995","journal-title":"Environ. Toxicol. Water Qual."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1002\/etc.3823","article-title":"Pseudoreplication and the usage of biomarkers in ecotoxicological bioassays","volume":"36","author":"Tincani","year":"2017","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2307\/2529204","article-title":"A cluster analysis method for grouping means in the analysis of variance","volume":"30","author":"Scott","year":"1974","journal-title":"Biometrics"},{"key":"ref_47","unstructured":"R Core Team (2013). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: http:\/\/www.R-project.org\/."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.5540\/tema.2014.015.01.0003","article-title":"ScottKnott: A package for performing the Scott-Knott clustering algorithm in R","volume":"15","author":"Jelihovschi","year":"2014","journal-title":"TEMA"},{"key":"ref_49","unstructured":"Morales, M. (2025, December 16). Sciplot: Scientific Graphing Functions for Factorial Designs. R Package Version 1.2-0, 2020. Available online: https:\/\/CRAN.R-project.org\/package=sciplot."},{"key":"ref_50","unstructured":"Brasil Minist\u00e9rio do Meio Ambiente, Conselho Nacional do Meio Ambiente (CONAMA) (2025, December 16). Resolu\u00e7\u00e3o n\u00ba 357, de 17 de Mar\u00e7o de 2005, Available online: https:\/\/conama.mma.gov.br\/?id=450&option=com_sisconama&task=arquivo.download."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s10695-015-0171-5","article-title":"Contaminant-induced oxidative stress in fish: A mechanistic approach","volume":"42","author":"Lushchak","year":"2016","journal-title":"Fish. Physiol. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1038\/s41423-020-00558-8","article-title":"Hepatic macrophages in liver homeostasis and diseases","volume":"18","author":"Wen","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_53","first-page":"359","article-title":"Gonadosomatic index (GSI), hepatosomatic index (HSI) and proportion of oocytes stadia as an indicator of rainbowfish Melanotaenia boesemani spawning season","volume":"2","author":"Hismayasari","year":"2015","journal-title":"Int. J. Fish. Aquat. Stud."},{"key":"ref_54","first-page":"524","article-title":"Determination of condition factor (K), somatic condition factor (Ks), hepatic and gonado somatic indices in the freshwater fish Notopterus notopterus","volume":"2","author":"Sudarshan","year":"2013","journal-title":"Int. J. Sci. Res."},{"key":"ref_55","first-page":"e17003","article-title":"Oxidative stress and histopathologic biomarkers of exposure to bisphenol-A in the freshwater fish Ctenopharyngodon idella","volume":"53","author":"Faheem","year":"2017","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Braunbeck, T., Hinton, D.E., and Streit, B. (1998). Cytological alterations in fish hepatocytes following in vivo and in vitro sublethal exposure to xenobiotics: Structural biomarkers of environmental contamination. Fish Ecotoxicology, Birkh\u00e4user.","DOI":"10.1007\/978-3-0348-8853-0_3"},{"key":"ref_57","first-page":"101863","article-title":"Using antioxidant changes in liver and gonads of Oreochromis niloticus as biomarkers for the assessment of heavy metals pollution at Sharkia Province, Egypt","volume":"46","author":"Ghobashy","year":"2021","journal-title":"Reg. Stud. Mar. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.chemosphere.2017.03.131","article-title":"Histological changes, lipid metabolism and oxidative stress in the liver of Bufo gargarizans exposed to cadmium concentrations","volume":"179","author":"Wu","year":"2017","journal-title":"Chemosphere"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Abdel-Latif, H.M.R., Dawood, M.A.O., Mahmoud, S.F., Shukry, M., Noreldin, A.E., Ghetas, H.A., and Khallaf, M.A. (2021). Copper oxide nanoparticles alter serum biochemical indices, induce histopathological alterations, and modulate transcription of cytokines, hsp70, and oxidative stress genes in Oreochromis niloticus. Animals, 11.","DOI":"10.20944\/preprints202101.0485.v1"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"126946","DOI":"10.1016\/j.chemosphere.2020.126946","article-title":"Insights into the development of hepatocellular fibrillar inclusions in European flounder (Platichthys flesus) from UK estuaries","volume":"256","author":"Bignell","year":"2020","journal-title":"Chemosphere"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"115095","DOI":"10.1016\/j.marpolbul.2023.115095","article-title":"Revealing the environmental pollution of two estuaries through histopathological biomarkers in five fishes from different trophic guilds of northeastern Brazil","volume":"192","author":"Lira","year":"2023","journal-title":"Mar. Pollut. Bull."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4067\/S0717-95022014000200055","article-title":"Morphology and histochemistry of the liver of carnivorous fish Hemisorbim platyrhynchos","volume":"32","author":"Faccioli","year":"2014","journal-title":"Int. J. Morphol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1177\/0748233713513490","article-title":"Enzymatic and histopathologic biomarkers in the flatfish Euryglossa orientalis from the northwestern Persian Gulf","volume":"32","author":"Chupani","year":"2016","journal-title":"Toxicol. Ind. Health"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ecoenv.2017.11.007","article-title":"Modulatory effects of green tea extract against the hepatotoxic effects of 4-nonylphenol in catfish (Clarias gariepinus)","volume":"149","author":"Sayed","year":"2018","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.envpol.2019.01.074","article-title":"Protective effects of a novel pyrazolecarboxamide derivative against lead nitrate\u2013induced oxidative stress and DNA damage in Clarias gariepinus","volume":"247","author":"Soliman","year":"2019","journal-title":"Environ. Pollut."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S0045-6535(03)00667-2","article-title":"Evaluation of impact of PAH on a tropical fish, Oreochromis mossambicus using multiple biomarkers","volume":"53","author":"Shailaja","year":"2003","journal-title":"Chemosphere"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1007\/s11356-012-1459-y","article-title":"Glutathione and its dependent enzymes\u2019 modulatory responses to toxic metals and metalloids in fish\u2014A review","volume":"20","author":"Srikanth","year":"2013","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.toxlet.2014.02.013","article-title":"Organochlorine pesticides and antioxidant enzymes are inversely correlated with liver enzyme gene expression in Cyprinus carpio","volume":"230","author":"Karaca","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"116600","DOI":"10.1016\/j.envres.2023.116600","article-title":"Review of cadmium toxicity effects on fish: Oxidative stress and immune responses","volume":"236","author":"Lee","year":"2023","journal-title":"Environ. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrgentox.2011.10.017","article-title":"DNA damage in fish (Anguilla anguilla) exposed to a glyphosate-based herbicide: Elucidation of organ specificity and the role of oxidative stress","volume":"743","author":"Guilherme","year":"2012","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3390\/jox12030018","article-title":"Pesticide pollution: Detrimental outcomes and possible mechanisms of fish exposure to common organophosphates and triazines","volume":"12","author":"Khatib","year":"2022","journal-title":"J. Xenobiotics"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.marpolbul.2018.04.028","article-title":"Liver melanomacrophage centres and CYP1A expression as response biomarkers to environmental pollution in European anchovy (Engraulis encrasicolus) from the western Mediterranean Sea","volume":"131","author":"Basilone","year":"2018","journal-title":"Mar. Pollut. Bull."},{"key":"ref_73","first-page":"e711","article-title":"Histopathological changes in Lithobates catesbeianus tadpoles used as biomarkers of pesticide poisoning","volume":"48","author":"Marcantonio","year":"2022","journal-title":"Bol. Inst. Pesca"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1095-8649.2000.tb02184.x","article-title":"Macrophage aggregates in gilthead sea bream fed copper, iron and zinc enriched diets","volume":"57","author":"Manera","year":"2000","journal-title":"J. Fish. Biol."},{"key":"ref_75","first-page":"473","article-title":"Effect of cadmium chloride on liver, spleen and kidney melano macrophage centres in Tilapia mossambica","volume":"30","author":"Suresh","year":"2009","journal-title":"J. Environ. Biol."},{"key":"ref_76","first-page":"11","article-title":"Melanomacrophage proliferation in the spleen of Nile tilapia (Oreochromis niloticus L.) as biomarker of insecticides loading from the waters of Laguna de Bay, Municipality of Bay, Laguna, Philippines","volume":"11","author":"Ocampo","year":"2015","journal-title":"Int. J. Agric. Resour. Gov. Ecol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/jfd.12102","article-title":"Liver melanomacrophage centres as indicators of Atlantic bluefin tuna, Thunus thynnus L. well-being","volume":"37","author":"Passantino","year":"2014","journal-title":"J. Fish. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0141-1136(02)00212-X","article-title":"Histopathological biomarkers in estuarine fish species for the assessment of biological effects of contaminants","volume":"55","author":"Stentiford","year":"2003","journal-title":"Mar. Environ. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3354\/meps07947","article-title":"Site-specific disease profiles in fish and their use in environmental monitoring","volume":"381","author":"Stentiford","year":"2009","journal-title":"Mar. Ecol. Prog. Ser."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3354\/meps08693","article-title":"Effect of age on liver pathology and other diseases in flatfish: Implications for assessment of marine ecological health status","volume":"411","author":"Stentiford","year":"2010","journal-title":"Mar. Ecol. Prog. Ser."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.marenvres.2015.02.004","article-title":"Histopathological assessment of liver and gonad pathology in continental slope fish from the northeast Atlantic Ocean","volume":"106","author":"Feist","year":"2015","journal-title":"Mar. Environ. Res."},{"key":"ref_82","unstructured":"Lala, V., Zubair, M., and Minter, D.A. (2024). Liver Function Tests, StatPearls Publishing."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/00004836-199409000-00008","article-title":"Serum lactic dehydrogenase in the differential diagnosis of acute hepatocellular injury","volume":"19","author":"Cassidy","year":"1994","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"108885","DOI":"10.1016\/j.fsi.2023.108885","article-title":"Liver fibrosis in fish research: From an immunological perspective","volume":"139","author":"Cao","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_85","unstructured":"Walker, H.K., Hall, W.D., and Hurst, J.W. (1990). Serum albumin and globulin. Clinical Methods: The History, Physical, and Laboratory Examinations, Butterworths. [3rd ed.]. Chapter 99."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jpen.1451","article-title":"Hypoalbuminemia: Pathogenesis and clinical significance","volume":"43","author":"Soeters","year":"2019","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.aquatox.2006.12.006","article-title":"A long-term copper exposure on freshwater ecosystem using lotic mesocosms: Primary producer community responses","volume":"81","author":"Roussel","year":"2007","journal-title":"Aquat. Toxicol."}],"container-title":["Journal of Xenobiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4713\/16\/5\/162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:42:36Z","timestamp":1787978556000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4713\/16\/5\/162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":87,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jox16050162"],"URL":"https:\/\/doi.org\/10.3390\/jox16050162","relation":{},"ISSN":["2039-4713"],"issn-type":[{"value":"2039-4713","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}