Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

The Effect of Sub-chronic Linuron Exposure on Thyroid, Liver, and Kidney Function in Male Wistar Rats

Author(s): Ifriqya Medila*, Ikram Toumi, Aicha Adaika, Aya Amrani, Messaouda Riab and Ouafa Boudebia

Volume 23, Issue 13, 2023

Published on: 05 June, 2023

Page: [1621 - 1627] Pages: 7

DOI: 10.2174/1871530323666230331104739

Price: $65

Abstract

Background: Herbicides are routinely used to control noxious plants. Most of these chemicals may cause toxicity and endocrine disruption in humans and wildlife.

Objective: This study aimed to evaluate the influence of linuron on thyroid hormone levels and some hepatic and renal parameters and organ (thyroid, liver and kidney) structures to assume their toxicity toward experimental animals and to evaluate the endocrine disrupting capacity of this chemical.

Methods: Two groups (8 rats each) were used for an in vivo study. The lot I served as control. Lot II was exposed to 40 mg/200 mg/day pesticide for 50 days. Changes in hepatic and renal parameters and histological structure were investigated in different treated groups.

Results: Data from this study showed that linuron altered thyroid function as evidenced by abnormal TSH, T4, and T3 levels. Furthermore, exposure to linuron induces a significant decrease in body weight and a significant increase in aspartate aminotransferase, alanine transaminase, total bilirubin, uric acid, creatinine, glutathione, and malondialdehyde. Previous data were confirmed through the histopathological examination of different organs.

Conclusions: The most used phenylurea herbicide, linuron, disrupted thyroid function at a 40 mg/200 mg/day dose and produced oxidative stress in the liver and kidney in male Wistar rats. The data of this study warrant further investigation.

Graphical Abstract

[1]
Gupta PK. Toxicity of Herbicides. (3rd ed.), Elsevier Inc. 2018.
[http://dx.doi.org/10.1016/B978-0-12-811410-0.00044-1]
[2]
Cycoń M.; Piotrowska-Seget, Z.; Kozdrój, J. Linuron effects on microbiological characteristics of sandy soils as determined in a pot study. Ann Microbiol 2010; 60(3): 439-49.
[http://dx.doi.org/10.1007/s13213-010-0061-0]
[3]
Dejonghe W, Berteloot E, Goris J, et al. Synergistic degradation of linuron by a bacterial consortium and isolation of a single linuron-degrading variovorax strain. Appl Environ Microbiol 2003; 69(3): 1532-41.
[http://dx.doi.org/10.1128/AEM.69.3.1532-1541.2003] [PMID: 12620840]
[4]
Albert O. Antiandrogens. Encycl Reprod 2018; 1(2001): 594-601.
[http://dx.doi.org/10.1016/B978-0-12-801238-3.64380-5]
[5]
Araújo EA. Determination of haloxyfop-methyl, linuron, and procymidone pesticides in carrot using SLE-LTP extraction and GC-MS. Food Anal Methods 2015; 9: 1344-52.
[http://dx.doi.org/10.1007/s12161-015-0315-3]
[6]
Caux P, Kent RA, Fan GT, Grande C. Canadian water quality guidelines for linuron. Environmental Toxicology and Water Quality. John Wiley & Sons, Inc 1997; pp. 1-41.
[7]
Maharaj S, El Ahmadie N, Rheingold S, et al. Sub-lethal toxicity assessment of the phenylurea herbicide linuron in developing zebrafish (Danio rerio) embryo/larvae. Neurotoxicol Teratol 2020; 81: 106917.
[http://dx.doi.org/10.1016/j.ntt.2020.106917] [PMID: 32712134]
[8]
Breugelmans P, Horemans B, Hofkens J, Springael D. Response to mixed substrate feeds of the structure and activity of a linuron-degrading triple-species biofilm. Res Microbiol 2010; 161(8): 660-6.
[http://dx.doi.org/10.1016/j.resmic.2010.06.006] [PMID: 20600856]
[9]
Spirhanzlova P, De Groef B, Nicholson FE, et al. Using short-term bioassays to evaluate the endocrine disrupting capacity of the pesticides linuron and fenoxycarb. Comp Biochem Physiol C Toxicol Pharmacol 2017; 200(June): 52-8.
[http://dx.doi.org/10.1016/j.cbpc.2017.06.006] [PMID: 28634053]
[10]
Calsolaro V, Pasqualetti G, Niccolai F, Caraccio N, Monzani F. Thyroid disrupting chemicals. Int J Mol Sci 2017; 18(12): 2583.
[http://dx.doi.org/10.3390/ijms18122583] [PMID: 29194390]
[11]
Requena M, López-Villén A, Hernández AF, Parrón T, Navarro Á, Alarcón R. Environmental exposure to pesticides and risk of thyroid diseases. Toxicol Lett 2019; 315: 55-63.
[http://dx.doi.org/10.1016/j.toxlet.2019.08.017] [PMID: 31445060]
[12]
Orton F, Lutz I, Kloas W, Routledge EJ. Endocrine disrupting effects of herbicides and pentachlorophenol: In vitro and in vivo evidence. Environ Sci Technol 2009; 43(6): 2144-50.
[http://dx.doi.org/10.1021/es8028928] [PMID: 19368227]
[13]
Shrestha S, Parks CG, Goldner WS, et al. Pesticide use and incident hypothyroidism in pesticide applicators in the agricultural health study. Environ Health Perspect 2018; 126(9): 097008.
[http://dx.doi.org/10.1289/EHP3194] [PMID: 30256155]
[14]
Chi HC, Tsai CY, Tsai MM, Yeh CT, Lin KH. Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases. J Biomed Sci 2019; 26(1): 24.
[http://dx.doi.org/10.1186/s12929-019-0517-x] [PMID: 30849993]
[15]
Cook JC, Mullin LS, Frame SR, Biegel LB. Investigation of a mechanism for Leydig cell tumorigenesis by linuron in rats. Toxicol Appl Pharmacol 1993; 119(2): 195-204.
[http://dx.doi.org/10.1006/taap.1993.1060] [PMID: 8480329]
[16]
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues thiobarbituric acid reaction. Anal Biochem 1979; 358: 351-8.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[17]
Beutler E, Kelly BM. The effect of sodium nitrite on red cell GSH. Experientia 1963; 19(2): 96-7.
[http://dx.doi.org/10.1007/BF02148042] [PMID: 13967892]
[18]
Landrigan PJ, Fuller R. Global health and environmental pollution. Int J Public Health 2015; 60(7): 761-2.
[http://dx.doi.org/10.1007/s00038-015-0706-7] [PMID: 26135237]
[19]
Nwozo S, Akpodono E, Oyinloye B. Plasma, erythrocyte membrane bound enzymes and tissue histopathology in male Wistar rats exposed to common insecticides. J Pestic Sci 2015; 40(1): 13-8.
[http://dx.doi.org/10.1584/jpestics.D14-065]
[20]
Hodge HC, Downs WL, Smith DW, Maynard EA, Clayton JW Jr, Pease HL. Oral toxicity of linuron (3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) in rats and dogs. Food Cosmet Toxicol 1968; 6(2): 171-83.
[http://dx.doi.org/10.1016/0015-6264(68)90199-5] [PMID: 5677664]
[21]
Kundu S, Pramanik M, Roy S, De J, Biswas A, Ray AK. Maintenance of brain thyroid hormone level during peripheral hypothyroid condition in adult rat. Life Sci 2006; 79(15): 1450-5.
[http://dx.doi.org/10.1016/j.lfs.2006.04.006] [PMID: 16698041]
[22]
Hernández AF, Bennekou SH, Hart A, Mohimont L, Wolterink G. Mechanisms underlying disruptive effects of pesticides on the thyroid function. Curr Opin Toxicol 2020; 19: 34-41.
[http://dx.doi.org/10.1016/j.cotox.2019.10.003]
[23]
Diamanti-Kandarakis E, Jean-Pierre B, Linda CG, et al. Endocrine-disrupting chemicals: An endocrine society scientific statement. Endocr Rev 2009; 30(4): 293-342.
[http://dx.doi.org/10.1210/er.2009-0002]
[24]
Schmutzler C. Endocrine disruptors and the thyroid gland-a combined in vitro and in vivo analysis of potential new biomarkers. Environ Health Perspect 2007; 115(S1): 77-83.
[http://dx.doi.org/10.1289/ehp.9369]
[25]
Lech JW. Interlaboratory validation of the 15-day adult intact male rat assay with linuron and phénobarbital. 2006. Available from: http://www.epa.gov/endo/pubs/interlab_charlesriver_fmal.pdf
[26]
Seidlová-Wuttke D, Jarry H, Christoffel J, Rimoldi G, Wuttke W. Effects of bisphenol-A (BPA), dibutylphtalate (DBP), benzophenone-2 (BP2), procymidone (Proc), and linurone (Lin) on fat tissue, a variety of hormones and metabolic parameters: A 3 months comparison with effects of estradiol (E2) in ovariectomized (ovx) rats. Toxicology 2005; 213(1-2): 13-24.
[http://dx.doi.org/10.1016/j.tox.2005.05.001] [PMID: 15951094]
[27]
Leemans M, Couderq S, Demeneix B, Fini JB. Pesticides with potential thyroid hormone-disrupting effects: A review of recent data. Front Endocrinol 2019; 10: 743.
[http://dx.doi.org/10.3389/fendo.2019.00743] [PMID: 31920955]
[28]
Ghassabian A. Disruption in thyroid signaling pathway  A mechanism for the effect of endocrine-disrupting chemicals on child neurodevelopment. Front Endocrinol 2018; 9: 204.
[http://dx.doi.org/10.3389/fendo.2018.00204]
[29]
Zhang J, Kamstra JH, Ghorbanzadeh M, Weiss JM, Hamers T, Andersson PL. In silico approach to identify potential thyroid hormone disruptors among currently known dust contaminants and their metabolites. Environ Sci Technol 2015; 49(16): 10099-107.
[http://dx.doi.org/10.1021/acs.est.5b01742] [PMID: 26207645]
[30]
Dong H, Wade MG. Application of a nonradioactive assay for high throughput screening for inhibition of thyroid hormone uptake via the transmembrane transporter MCT8. Toxicol In Vitro 2017; 40: 234-42.
[http://dx.doi.org/10.1016/j.tiv.2017.01.014] [PMID: 28119167]
[31]
Yang FW, Li YX, Ren FZ, Luo J, Pang GF. Assessment of the endocrine-disrupting effects of organophosphorus pesticide triazophos and its metabolites on endocrine hormones biosynthesis, transport and receptor binding in silico. Food Chem Toxicol 2019; 133(17): 110759.
[http://dx.doi.org/10.1016/j.fct.2019.110759] [PMID: 31421215]
[32]
Hofmann PJ, Schomburg L, Köhrle J. Interference of endocrine disrupters with thyroid hormone receptor-dependent transactivation. Toxicol Sci 2009; 110(1): 125-37.
[http://dx.doi.org/10.1093/toxsci/kfp086] [PMID: 19403856]
[33]
de Souza JS, Kizys MML, da Conceição RR, et al. Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats. Toxicology 2017; 377: 25-37.
[http://dx.doi.org/10.1016/j.tox.2016.11.005] [PMID: 27916585]
[34]
Mahjoubi-Samet A, Soussia L, Fadhel G, Zeghal N. Dimethoate effects on thyroid function in suckling rats. Ann Endocrinol 2005; 66(2 Pt. 1): 96-104.
[http://dx.doi.org/10.1016/S0003-4266(05)81705-6]
[35]
Lu M, Du J, Zhou P, Chen H, Lu C, Zhang Q. Endocrine disrupting potential of fipronil and its metabolite in reporter gene assays. Chemosphere 2015; 120: 246-51.
[http://dx.doi.org/10.1016/j.chemosphere.2014.07.015] [PMID: 25112704]
[36]
Benedetti AL, Vituri CL, Trentin AG, Domingues MAC, Alvarez-Silva M. The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate-Biocarb®. Toxicol Lett 2004; 153(2): 227-32.
[http://dx.doi.org/10.1016/j.toxlet.2004.04.008] [PMID: 15451553]
[37]
Duff B. Veterinary clinical pathology. Aust Vet J 1976; 52(5): 227-7.
[http://dx.doi.org/10.1111/j.1751-0813.1976.tb00073.x]
[38]
Dedeke GA, Owagboriaye FO, Ademolu KO, Olujimi OO, Aladesida AA. Comparative assessment on mechanism underlying renal toxicity of commercial formulation of roundup herbicide and glyphosate alone in male albino rat. Int J Toxicol 2018; 37(4): 285-95.
[http://dx.doi.org/10.1177/1091581818779553] [PMID: 29890881]
[39]
Refaie AA, Shalby AB, Kassem SM, Khalil WKB. DNA damage and expression profile of genes associated with nephrotoxicity induced by butralin and ameliorating effect of arabic gum in female rats. Appl Biochem Biotechnol 2021; 193(11): 3454-68.
[http://dx.doi.org/10.1007/s12010-021-03607-8] [PMID: 34240313]
[40]
Owagboriaye FO, Dedeke GA, Ademolu KO, Olujimi OO, Ashidi JS, Adeyinka AA. Reproductive toxicity of Roundup herbicide exposure in male albino rat. Exp Toxicol Pathol 2017; 69(7): 461-8.
[http://dx.doi.org/10.1016/j.etp.2017.04.007] [PMID: 28473188]
[41]
Uren Webster TM, Perry MH, Santos EM. The herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout. Environ Sci Technol 2015; 49(5): 3110-8.
[http://dx.doi.org/10.1021/es505498u] [PMID: 25633873]
[42]
Gokcimen A, Gulle K, Demirin H, Bayram D, Kocak A, Altuntas I. Effects of diazinon at different doses on rat liver and pancreas tissues. Pestic Biochem Physiol 2007; 87(2): 103-8.
[http://dx.doi.org/10.1016/j.pestbp.2006.06.011]
[43]
Oulmi Y, Negele RD, Braunbeck T. Cytopathology of liver and kidney in rainbow trout Oncorhynchus mykiss after long-term exposure to sublethal concentrations of linuron. Dis Aquat Organ 1995; 21: 35-52.
[http://dx.doi.org/10.3354/dao021035]
[44]
U.S. EPA, 2007d.. 15-Day intact adult male rat assay, EDSP integrated summary report; U.S. Environmental Protection Agency, 2007. Available from: https://www.epa.gov/sites/default/files/2015-08/documents/edsp_comprehesive_management_plan_021414_f.pdf
[45]
Lambright C, Ostby J, Bobseine K, et al. Cellular and molecular mechanisms of action of linuron: An antiandrogenic herbicide that produces reproductive malformations in male rats. Toxicol Sci 2000; 56(2): 389-99.
[http://dx.doi.org/10.1093/toxsci/56.2.389] [PMID: 10910998]
[46]
O’Connor JC, Frame SR, Ladics GS. Evaluation of a 15-day screening assay using intact male rats for identifying antiandrogens. Toxicol Sci 2002; 69(1): 92-108.
[http://dx.doi.org/10.1093/toxsci/69.1.92] [PMID: 12215663]
[47]
Ashby J, Lefevre PA, Tinwell H, Odum J, Owens W. Testosterone-stimulated weanlings as an alternative to castrated male rats in the hershberger anti-androgen assay. Regul Toxicol Pharmacol 2004; 39(2): 229-38.
[http://dx.doi.org/10.1016/j.yrtph.2004.02.001] [PMID: 15041151]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy