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Sex-specific effects of fluoride and lead exposures on histology, antioxidant physiology, and immune system in the liver of zebrafish (Danio rerio)

Abstract

Fluoride and Pb are both toxic to organisms; however, their combination effects and the corresponding toxic mechanisms remain unclear. In this study, male and female zebrafish (1:1) were evaluated to understand the effects of F and Pb alone and combined on growth, tissue microstructure, oxidative stress, and immune system functions of the liver. Four different groups and two exposure periods were compared: control group (C group), 80 mg/L fluoride group (F group), 60 mg/L lead group (Pb group), and 80 mg/L fluoride + 60 mg/L lead group (F + Pb group) for 45 and 90 days. The results indicated that F and Pb reduced growth performances; F + Pb treatment inhibited the growth performance traits of male zebrafish more than those of female zebrafish. Histopathological examination revealed large areas with focal necrosis, hepatocytes with karyolysis, and pycnotic nuclei in zebrafish exposed to F and Pb. The oxidative balance indices in the liver in the F and Pb groups were disturbed. F + Pb co-exposure aggravated oxidative stress in a time-dependent manner. The most serious oxidative stress was observed in the male zebrafish of the F + Pb group. Moreover, F and Pb exposure of male zebrafish increased pro-inflammatory and anti-inflammatory cytokines expression, which was decreased after 90 days of exposure. These results demonstrated that both F and Pb could damage the liver via downstream alterations in the activities of immune-related enzymes and in the levels of immune-related genes. F and Pb showed synergistic or additive effects. Male zebrafish were found to be more sensitive to F and Pb than female zebrafish.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Agalakova NI, Gusev GP (2012) Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. ISRN Cell Biol 2012:1–16. https://doi.org/10.5402/2012/403835

  • Almaida-Pagan PF, Lucas-Sanchez A, Tocher DR (2014) Changes in mitochondrial membrane composition and oxidative status during rapid growth, maturation and aging in zebrafish, Danio rerio. Biochim Biophys Acta 1841(7):1003–1011. https://doi.org/10.1016/j.bbalip.2014.04.004

  • Annabi Berrahal A, Nehdi A, Hajjaji N, Gharbi N, El-Fazaa S (2007) Antioxidant enzymes activities and bilirubin level in adult rat treated with lead. C R Biol 330(8):581–588. https://doi.org/10.1016/jcrvi200705007

  • Barbier L, Ferhat M, Salame E, Robin A, Herbelin A, Gombert JM, Barbarin A (2019) Interleukin-1 family cytokines: keystones in liver inflammatory diseases. Front Immunol 10:2014. https://doi.org/10.3389/fimmu201902014

  • Bohnacker S, Hildenbrand K, Aschenbrenner I, Muller SI, Bieren JE, Feige MJ (2020) Influence of glycosylation on IL-12 family cytokine biogenesis and function. Mol Immunol 126:120–128. https://doi.org/10.1016/jmolimm202007015

  • Borah KK, Bhuyan B, Sarma HP (2010) Lead, arsenic, fluoride, and iron contamination of drinking water in the tea garden belt of Darrang district, Assam, India. Environ Monit Assess 169(1–4):347–352. https://doi.org/10.1007/s10661-009-1176-2

  • Boskabady M, Marefati N, Farkhondeh T, Shakeri F, Farshbaf A, Boskabady MH (2018) The effect of environmental lead exposure on human health and the contribution of inflammatory mechanisms, a review. Environ Int 120:404–420. https://doi.org/10.1016/jenvint201808013

  • Cao J, Chen J, Wang J, Jia R, Xue W, Luo Y, Gan X (2013) Effects of fluoride on liver apoptosis and Bcl-2, Bax protein expression in freshwater teleost, Cyprinus carpio. Chemosphere 91(8):1203–1212. https://doi.org/10.1016/jchemosphere201301037

  • Cao J, Chen J, Wang J, Klerks P, Xie L (2014) Effects of sodium fluoride on MAPKs signaling pathway in the gills of a freshwater teleost, Cyprinus carpio. Aquat Toxicol 152:164–172. https://doi.org/10.1016/jaquatox201404007

  • Cao J, Feng C, Xie L, Li L, Chen J, Yun S, Luo Y (2020) Sesamin attenuates histological alterations, oxidative stress and expressions of immune-related genes in liver of zebrafish (Danio rerio) exposed to fluoride. Fish Shellfish Immunol 106:715–723. https://doi.org/10.1016/jfsi202008039

  • Cao X, Bi R, Song Y (2017) Toxic responses of cytochrome P450 sub-enzyme activities to heavy metals exposure in soil and correlation with their bioaccumulation in Eisenia fetida. Ecotoxicol Environ Saf 144:158–165. https://doi.org/10.1016/jecoenv201706023

  • Chaplin DD (2010) Overview of the immune response. J Allergy Clin Immunol 125(2 Suppl 2):S3–23. https://doi.org/10.1016/jjaci200912980

  • Charkiewicz AE, Backstrand JR (2020) Lead toxicity and pollution in Poland. Int J Environ Res Public Health 17(12). https://doi.org/10.3390/ijerph17124385

  • Chen J, Cao J, Wang J, Jia R, Xue W, Xie L (2015) Fluoride-induced apoptosis and expressions of caspase proteins in the kidney of carp (Cyprinus carpio). Environ Toxicol 30(7):769–781. https://doi.org/10.1002/tox21956

  • Chen X, Choi IY, Chang TS, Noh YH, Shin CY, Wu CF, Kim WK (2009) Pretreatment with interferon-gamma protects microglia from oxidative stress via up-regulation of Mn-SOD. Free Radic Biol Med 46(8):1204–1210. https://doi.org/10.1016/jfreeradbiomed200901027

  • Chen S, Chen H, Du Q, Shen J (2020) Targeting myeloperoxidase (MPO) mediated oxidative stress and inflammation for reducing brain ischemia injury: potential application of natural compounds. Front Physiol 11:433. https://doi.org/10.3389/fphys202000433

  • Chen J, Luo Y, Cao J, Xie L (2021) Fluoride exposure changed the expression of microRNAs in gills of male zebrafish (Danio rerio). Aquat Toxicol 233. https://doi.org/10.1016/jaquatox2021105789

  • Chen QL, Sun YL, Liu ZH, Li YW (2017) Sex-dependent effects of subacute mercuric chloride exposure on histology, antioxidant status and immune-related gene expression in the liver of adult zebrafish (Danio rerio). Chemosphere 188:1–9. https://doi.org/10.1016/jchemosphere201708148

  • Chen J, Xue W, Cao J, Song J, Jia R, Li M (2016) Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio). Aquat Toxicol 171:48–58. https://doi.org/10.1016/jaquatox201512010

  • Chen L, Zhu B, Guo Y, Xu T, Lee JS, Qian PY, Zhou B (2016) High-throughput transcriptome sequencing reveals the combined effects of key e-waste contaminants, decabromodiphenyl ether (BDE-209) and lead, in zebrafish larvae. Environ Pollut 214:324–333. https://doi.org/10.1016/jenvpol201604040

  • Dai W, Liu S, Fu L, Du H, Xu Z (2012) Lead (Pb) accumulation, oxidative stress and DNA damage induced by dietary Pb in tilapia (Oreochromis niloticus). Aquac Res 43(2):208–214. https://doi.org/10.1111/j1365-2109201102817x

  • Eder K, Clifford M, Hedrick R, Kohler H, Werner I (2008) Expression of immune-regulatory genes in juvenile Chinook salmon following exposure to pesticides and infectious hematopoietic necrosis virus (IHNV). Fish Shellfish Immunol 25(5):508–516. https://doi.org/10.1016/jfsi200807003

  • Flohé L, Günzler AW (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–120. https://doi.org/10.1016/s0076-6879(84)05015-1

  • Fordyce FM, Vrana K, Zhovinsky E, Povoroznuk V, Toth G, Hope BC, Baker J (2007) A health risk assessment for fluoride in Central Europe. Environ Geochem Health 29(2):83–102. https://doi.org/10.1007/s10653-006-9076-7

  • Fu F, Wang L (2020) Molecular cloning, characterization of JunB in Schizothorax prenanti and its roles in responding to Aeromonas hydrophila infection. Int J Biol Macromol 164:2788–2794. https://doi.org/10.1016/jijbiomac202008012

  • Fu Q, Zeng Q, Li Y, Yang Y, Li C, Liu S, Liu Z (2017) The chemokinome superfamily in channel catfish: I CXC subfamily and their involvement in disease defense and hypoxia responses. Fish Shellfish Immunol 60:380–390. https://doi.org/10.1016/jfsi201612004

  • Gabay C (2006) Interleukin-6 and chronic inflammation. Arthritis Res Ther 8(Suppl 2):S3. https://doi.org/10.1186/ar1917

  • Gagnon MM, Rawson CA (2017) Bioindicator species for EROD activity measurements: a review with Australian fish as a case study. Ecol Indic 73:166–180. https://doi.org/10.1016/jecolind201609015

  • Geier DA, Kern JK, Geier MR (2017) Blood lead levels and learning disabilities: a cross-sectional study of the 2003–2004 National Health and Nutrition Examination Survey (NHANES). Int J Environ Res Public Health 14(10). https://doi.org/10.3390/ijerph14101202

  • Gobi N, Vaseeharan B, Chen JC, Rekha R, Vijayakumar S, Anjugam M, Iswarya A (2018) Dietary supplementation of probiotic Bacillus licheniformis Dahb1 improves growth performance, mucus and serum immune parameters, antioxidant enzyme activity as well as resistance against Aeromonas hydrophila in tilapia Oreochromis mossambicus. Fish Shellfish Immunol 74:501–508.8. https://doi.org/10.1016/jfsi201712066

  • Heinrich P, Braunbeck T (2020) Microplastic particles reduce EROD-induction specifically by highly lipophilic compounds in RTL-W1 cells. Ecotoxicol Environ Saf 189:110041. https://doi.org/10.1016/jecoenv2019110041

  • Hemdan NY, Emmrich F, Adham K, Wichmann G, Lehmann I, El-Massry A, Sack U (2005) Dose-dependent modulation of the in vitro cytokine production of human immune competent cells by lead salts. Toxicol Sci 86(1):75–83. https://doi.org/10.1093/toxsci/kfi177

  • Janssens L, Stoks R, Costantini D (2020) Oxidative stress mediates rapid compensatory growth and its costs. Funct Ecol 34(10):2087–2097. https://doi.org/10.1111/1365-243513616

  • Jin H, Ji C, Ren F, Aniagu S, Tong J, Jiang Y, Chen T (2020) AHR-mediated oxidative stress contributes to the cardiac developmental toxicity of trichloroethylene in zebrafish embryos. J Hazard Mater 385:121521. https://doi.org/10.1016/jjhazmat2019121521

  • Kasten-Jolly J, Lawrence DA (2017) Sex-specific effects of developmental lead exposure on the immune-neuroendocrine network. Toxicol Appl Pharmacol 334:142–157. https://doi.org/10.1016/jtaap201709009

  • Kataba A, Botha TL, Nakayama SMM, Yohannes YB, Ikenaka Y, Wepener V, Ishizuka M (2020) Acute exposure to environmentally relevant lead levels induces oxidative stress and neurobehavioral alterations in larval zebrafish (Danio rerio). Aquat Toxicol 227:105607. https://doi.org/10.1016/jaquatox2020105607

  • Kaur R, Saxena A, Batra M (2017) A review study on fluoride toxicity in water and fishes: current status, toxicology and remedial measures. Int J Environ Agric Biotechnol 2(1):456–466. https://doi.org/10.22161/ijeab/2158

  • Khandare AL, Validandi V, Gourineni SR, Gopalan V, Nagalla B (2018) Dose-dependent effect of fluoride on clinical and subclinical indices of fluorosis in school going children and its mitigation by supply of safe drinking water for 5 years: an Indian study. Environ Monit Assess 190(3):110. https://doi.org/10.1007/s10661-018-6501-1

  • Kim JH, Kang JC (2016) The immune responses in juvenile rockfish, Sebastes schlegelii for the stress by the exposure to the dietary lead (II). Environ Toxicol Pharmacol 46:211–216. https://doi.org/10.1016/jetap201607022

  • Kumar A, Kumar AMMSC, Chaturvedi AK, Shabnam AA, Subrahmanyam G, Yadav, KK (2020) Lead toxicity: health hazards, influence on food chain, and sustainable remediation approaches. Int J Environ Res Public Health 17(7). https://doi.org/10.3390/ijerph17072179

  • Lau KH, Baylink DJ (1998) Molecular mechanism of action of fluoride on bone cells. J Bone Miner Res 13(11):1660–1667. https://doi.org/10.1359/jbmr199813111660

  • Lee JW, Choi H, Hwang UK, Kang JC, Kang YJ, Kim KI, Kim JH (2019) Toxic effects of lead exposure on bioaccumulation, oxidative stress, neurotoxicity, and immune responses in fish: a review. Environ Toxicol Pharmacol 68:101–108. https://doi.org/10.1016/jetap201903010

  • Li M, Cao J, Chen J, Song J, Zhou B, Feng C, Wang J (2016) Waterborne fluoride exposure changed the structure and the expressions of steroidogenic-related genes in gonads of adult zebrafish (Danio rerio). Chemosphere 145:365–375. https://doi.org/10.1016/jchemosphere201511041

  • Li Y, Liu Z, Li M, Jiang Q, Wu D, Huang Y, Zhao Y (2020) Effects of nanoplastics on antioxidant and immune enzyme activities and related gene expression in juvenile Macrobrachium nipponense. J Hazard Mater 398:122990. https://doi.org/10.1016/jjhazmat2020122990

  • Liu Z, Yu P, Cai M, Wu D, Zhang M, Chen M, Zhao Y (2019) Effects of microplastics on the innate immunity and intestinal microflora of juvenile Eriocheir sinensis. Sci Total Environ 685:836–846. https://doi.org/10.1016/jscitotenv201906265

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408. https://doi.org/10.1006/meth20011262

  • Lopez Nadal A, Ikeda-Ohtsubo W, Sipkema D, Peggs D, McGurk C, Forlenza M, Brugman S (2020) Feed, microbiota, and gut immunity: using the zebrafish model to understand fish health. Front Immunol 11:114. https://doi.org/10.3389/fimmu202000114

  • Lu Y, Luo Q, Cui H, Deng H, Kuang P, Liu H, Zhao L (2017) Sodium fluoride causes oxidative stress and apoptosis in the mouse liver. Aging 9(6):1623–1639. https://doi.org/10.18632/aging101257

  • Maratta A, Vázquez S, López A, Augusto M, Pacheco PH (2016) Lead preconcentration by solid phase extraction using oxidized carbon xerogel and spectrophotometric determination with dithizone. Microchem J 128:166–171. https://doi.org/10.1016/jmicroc201604017

  • Martin-Mateos R, Alvarez-Mon M, Albillos A (2019) Dysfunctional immune response in acute-on-chronic liver failure: it takes two to tango. Front Immunol 10:973. https://doi.org/10.3389/fimmu201900973

  • Maruyama K (2003) Structure and characterization of hamster IL-12 p35 and p40. Mol Immunol 40(6):319–326. https://doi.org/10.1016/s0161-5890(03)00165-2

  • Mondal P, Shaw P, Bandyopadhyay A, Dey Bhowmik A, Chakraborty A, Sudarshan M, Chattopadhyay A (2019) Mixture effect of arsenic and fluoride at environmentally relevant concentrations in zebrafish (Danio rerio) liver: Expression pattern of Nrf2 and related xenobiotic metabolizing enzymes. Aquat Toxicol 213:105219. https://doi.org/10.1016/jaquatox201906002

  • Moreno-Navarrete JM, Latorre J, Lluch A, Ortega FJ, Comas F, Arnoriaga-Rodriguez M, Fernandez-Real JM (2020) Lysozyme is a component of the innate immune system linked to obesity associated-chronic low-grade inflammation and altered glucose tolerance. Clin Nutr. https://doi.org/10.1016/jclnu202008036

  • Mukhopadhyay D, Chattopadhyay A (2014) Induction of oxidative stress and related transcriptional effects of sodium fluoride in female zebrafish liver. Bull Environ Contam Toxicol 93(1):64–70. https://doi.org/10.1007/s00128-014-1271-0

  • Niu R, Sun Z, Cheng Z, Li Z, Wang J (2009) Decreased learning ability and low hippocampus glutamate in offspring rats exposed to fluoride and lead. Environ Toxicol Pharmacol 28:254–258. https://doi.org/10.1016/j.etap.2009.04.012

  • Olmo R, Teijon C, Muniz E, Beneit JV, Villarino AL, Blanco MD (2012) Modulation of lysozyme activity by lead administered by different routes. In vitro study and analysis in blood, kidney, and lung. Biol Trace Elem Res 149:405–411. https://doi.org/10.1007/s12011-012-9446-1

  • Ozsvath DL (2008) Fluoride and environmental health: a review. Rev Environ Sci Bio/Technol 8(1):59–79. https://doi.org/10.1007/s11157-008-9136-9

  • Panov VG, Katsnelson BA, Varaksin AN, Privalova LI, Kireyeva EP, Sutunkova MP, Beresneva OY (2015) Further development of mathematical description for combined toxicity: a case study of lead-fluoride combination. Toxicol Rep 2:297–307. https://doi.org/10.1016/jtoxrep201502002

  • Park K, Han EJ, Ahn G, Kwak IS (2020) Effects of thermal stress-induced lead (Pb) toxicity on apoptotic cell death, inflammatory response, oxidative defense, and DNA methylation in zebrafish (Danio rerio) embryos. Aquat Toxicol 224:105479. https://doi.org/10.1016/j.aquatox.2020.105479

    CAS  Article  Google Scholar 

  • Pasupuleti VR, Arigela CS, Gan SH, Salam SKN, Krishnan KT, Rahman NA, Jeffree MS (2020) A review on oxidative stress, diabetic complications, and the roles of honey polyphenols. Oxid Med Cell Longev 2020:8878172. https://doi.org/10.1155/2020/8878172

  • Patnaik A, Axford L, Deng L, Cohick E, Ren X, Loi S, Patterson AW (2020) Discovery of a novel indole pharmacophore for the irreversible inhibition of myeloperoxidase (MPO). Bioorg Med Chem 28:12. https://doi.org/10.1016/jbmc2020115548

  • Pukanha K, Yimthiang S, Kwanhian W (2020) The immunotoxicity of chronic exposure to high levels of lead: an ex vivo investigation. Toxics 8(3). https://doi.org/10.3390/toxics8030056

  • Radbin R, Vahedi F, Chamani J (2014) The influence of drinking-water pollution with heavy metal on the expression of IL-4 and IFN-gamma in mice by real-time polymerase chain reaction. Cytotechnology 66(5):769–777. https://doi.org/10.1007/s10616-013-9626-7

  • Saurabh S, Sahoo PK (2008) Lysozyme: an important defence molecule of fish innate immune system. Aquac Res 39(3):223–239. https://doi.org/10.1111/j1365-2109200701883x

  • Sawan RMM, Leite GAS, Saraiva MCP, Barbosa F, Tanus-Santos JE, Gerlach RF (2010) Fluoride increases lead concentrations in whole blood and in calcified tissues from lead-exposed rats. Toxicology 271(1–2):21–26. https://doi.org/10.1016/jtox201002002

  • Shen J, Gagliardi S, McCoustra MRS, Arrighi V (2016) Effect of humic substances aggregation on the determination of fluoride in water using an ion selective electrode. Chemosphere 159:66–71. https://doi.org/10.1016/jchemosphere201605069

  • Shi L, Wang N, Hu X, Yin D, Wu C, Liang H, Cao H (2020) Acute toxic effects of lead (Pb(2+)) exposure to rare minnow (Gobiocypris rarus) revealed by histopathological examination and transcriptome analysis. Environ Toxicol Pharmacol 78:103385. https://doi.org/10.1016/jetap2020103385

  • Shi X, Zhuang P, Zhang L, Feng G, Chen L, Liu J, Qu L, Wang R (2009) The bioaccumulation of fluoride ion (F-) in Siberian sturgeon (Acipenser baerii) under laboratory conditions. Chemosphere 75:376–380. https://doi.org/10.1016/j.chemosphere.2008.12.042

    CAS  Article  Google Scholar 

  • Si LF, Wang CC, Guo SN, Zheng JL, Xia H (2019) The lagged effects of environmentally relevant zinc on non-specific immunity in zebrafish. Chemosphere 214:85–93. https://doi.org/10.1016/jchemosphere201809050

  • Singaram G, Harikrishnan T, Chen FY, Bo J, Giesy JP (2013) Modulation of immune-associated parameters and antioxidant responses in the crab (Scylla serrata) exposed to mercury. Chemosphere 90(3):917–928. https://doi.org/10.1016/jchemosphere201206031

  • Strunecka A, Strunecky O (2020) Mechanisms of fluoride toxicity: from enzymes to underlying integrative networks. Appl Sci 10(20). https://doi.org/1103390/app10207100

  • Tiberio L, Del Prete A, Schioppa T, Sozio F, Bosisio D, Sozzani S (2018) Chemokine and chemotactic signals in dendritic cell migration. Cell Mol Immunol 15(4):346–352. https://doi.org/10.1038/s41423-018-0005-3

  • Wang T, Wen X, Hu Y, Zhang X, Wang D, Yin S (2019) Copper nanoparticles induced oxidation stress, cell apoptosis and immune response in the liver of juvenile Takifugu fasciatus. Fish Shellfish Immunol 84:648–655. https://doi.org/10.1016/j.fsi.2018.10.053

    CAS  Article  Google Scholar 

  • Whyte JJ, Jung RE, Schmitt CJ, Tillitt DE (2000) Ethoxyresorufin-O-deethylase (EROD) activity in fish as a biomarker of chemical exposure. Crit Rev Toxicol 30(4):347–570. https://doi.org/10.1080/10408440091159239

  • Wu Q, Leung JY, Geng X, Chen S, Huang X, Li H, Huang Z, Zhu L, Chen J, Lu Y (2015) Heavy metal contamination of soil and water in the vicinity of an abandoned e-waste recycling site: implications for dissemination of heavy metals. Sci Total Environ 506-507:217–225. https://doi.org/10.1016/j.scitotenv.2014.10.121

    CAS  Article  Google Scholar 

  • Wu L, Yu Q, Zhang G, Wu F, Zhang Y, Yuan C, Zhang T, Wang Z (2019) Single and combined exposures of waterborne Cu and Cd induced oxidative stress responses and tissue injury in female rare minnow (Gobiocypris rarus). Comp Biochem Physiol C Toxicol Pharmacol 222:90–99. https://doi.org/10.1016/j.cbpc.2019.04.013

    CAS  Article  Google Scholar 

  • Xu X, Cui Z, Wang S (2018) Joint toxicity on hepatic detoxication enzymes in goldfish (Carassius auratus) exposed to binary mixtures of lead and paraquat. Environ Toxicol Pharmacol 62:60–68. https://doi.org/10.1016/jetap201806005

  • Yamaguchi S, Miura C, Ito A, Agusa T, Iwata H, Tanabe S, Miura T (2007) Effects of lead, molybdenum, rubidium, arsenic and organochlorines on spermatogenesis in fish: monitoring at Mekong Delta area and in vitro experiment. Aquat Toxicol 83(1):43–51. https://doi.org/10.1016/jaquatox200703010

  • Yan W, Hamid N, Deng S, Jia PP, Pei DS (2020) Individual and combined toxicogenetic effects of microplastics and heavy metals (Cd, Pb, and Zn) perturb gut microbiota homeostasis and gonadal development in marine medaka (Oryzias melastigma). J Hazard Mater 397:122795. https://doi.org/10.1016/jjhazmat2020122795

  • Yu Y, Duan J, Li Y, Li Y, Jing L, Yang M, Sun Z (2017) Silica nanoparticles induce liver fibrosis via TGF-beta1/Smad3 pathway in ICR mice. Int J Nanomed 12:6045–6057. https://doi.org/10.2147/IJNS132304

  • Yu L, Yu Y, Yin R, Duan H, Qu D, Tian F, Zhai Q (2021) Dose-dependent effects of lead induced gut injuries: an in vitro and in vivo study. Chemosphere 266:129130. https://doi.org/10.1016/jchemosphere2020129130

  • Yu H, Zhang Y, Zhang P, Shang X, Lu Y, Fu Y, Li Y (2021) Effects of fluorine on intestinal structural integrity and microbiota composition of common carp. Biol Trace Elem Res 199:3489–3496. https://doi.org/10.1007/s12011-020-02456-6

  • Yu YM, Zhou BH, Yang YL, Guo CX, Zhao J, Wang HW (2021) Estrogen deficiency aggravates fluoride-induced liver damage and lipid metabolism disorder in rats. Biol Trace Elem Res 48:377–385. https://doi.org/10.1007/s12011-021-02857-1

    CAS  Article  Google Scholar 

  • Zhang D, Tang J, Zhang J, Zhang L, Hu CX (2019) Responses of pro- and anti-inflammatory cytokines in zebrafish liver exposed to sublethal doses of Aphanizomenon flosaquae DC-1 aphantoxins. Aquat Toxicol 215:105269. https://doi.org/10.1016/jaquatox2019105269

  • Zhang Y, Zhang P, Shang X, Lu Y, Li Y (2020) Exposure of lead on intestinal structural integrity and the diversity of gut microbiota of common carp. Comp Biochem Physiol C Toxicol Pharmacol 239:108877. https://doi.org/10.1016/j.cbpc.2020.108877

  • Zhu QL, Li WY, Zheng JL (2018) Life-cycle exposure to cadmium induced compensatory responses towards oxidative stress in the liver of female zebrafish. Chemosphere 210:949–957. https://doi.org/10.1016/jchemosphere201807095

  • Zuo H, Chen L, Kong M, Qiu L, Lu P, Wu P, Chen K (2018) Toxic effects of fluoride on organisms. Life Sci 198:18–24. https://doi.org/10.1016/jlfs201802001

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Acknowledgements

This study was supported by the Shanxi Scholarship Council of China (2020-061), the Shanxi Provincial Key Research and Development Project (201903D221009), and the National Natural Science Foundation of China (31502141; 31440087).

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GW: data curation, writing—original draft preparation, methodology. TW: data curation, conceptualization, methodology. XZ: formal analysis, validation. JC: data curation, methodology; CF: conceptualization; SY: formal analysis; YC: formal analysis; FC: methodology; JC: supervision, project administration, writing—reviewing and editing.

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Correspondence to Jinling Cao.

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Wang, G., Wang, T., Zhang, X. et al. Sex-specific effects of fluoride and lead exposures on histology, antioxidant physiology, and immune system in the liver of zebrafish (Danio rerio). Ecotoxicology 31, 396–414 (2022). https://doi.org/10.1007/s10646-022-02519-5

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Keywords

  • Fluoride
  • Lead
  • Liver
  • Sex-specific effect
  • Antioxidant physiology
  • Immune systems