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Tibial growth plate vascularization is inhibited by the dithiocarbamate pesticide thiram in chickens: potential relationship to peripheral platelet counts alteration

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Abstract

The widespread use of thiram has raised concerns for health and its toxic effects, but the underlying toxicity mechanism on platelets and bones is poorly defined. Here, we found a significant increase in the number of platelets in chickens with the thiram intake, due to the increased expression of thrombopoietin mRNA in the dysfunction liver. Furthermore, the decreased vascular distribution and cell death of chondrocytes in the tibial growth plates (TGPs) were observed, resulting in bone growth inhibition, which is associated with the abnormal activation of platelets leading to the extraordinary decrease of vascular endothelial growth factor A (VEGFA) and angiopoietin-1 protein were released and their corresponding receptors VEGFR2 and Tie-2 expressions were also reduced in the TGPs. Taken together, these findings revealed that thiram has an adverse effect on bones and platelets, which may have a high risk of thrombosis and osteoarthritis.

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Abbreviations

AA chickens:

Arbor Acres chickens

ALT:

Alanine aminotransferase

AST:

Aspartate transaminase

ALP:

Alkaline phosphatase

Ang-1:

Angiopoietin-1

CBCs:

Complete blood counts

CDW:

Chondrocyte distribution width

ELISA:

Enzyme-linked immunosorbent assay

qRT-PCR:

Quantitative RT-PCR

H&E:

Hematoxylin and eosin

HPCs:

Hematopoietic progenitor cells

HZ:

Hypertrophic chondrocyte zone

IL-1:

Interleukin-1

MPV:

Mean platelet volume

PCT:

Plateletcrit

PDW:

Platelet distribution width

PLT:

Platelet

SDH:

Succinate dehydrogenase

TPO:

Thrombopoietin

TGPs:

Tibial growth plates

VEGFA:

Vascular endothelial growth factor A

References

  • Almontebecerril M, Navarrogarcia F, Gonzalezrobles A, Vegalopez MA, Lavalle C, Kouri JB (2010) Cell death of chondrocytes is a combination between apoptosis and autophagy during the pathogenesis of osteoarthritis within an experimental model. Apoptosis 15:631–638

    CAS  Google Scholar 

  • Bambace NM, Levis JE, Holmes CE (2010) The effect of p2y-mediated platelet activation on the release of vegf and endostatin from platelets. Platelets 21:85–93

    CAS  Google Scholar 

  • Charlier E, Relic B, Deroyer C, Malaise O, Neuville S, Collée J, Malaise MG, De Seny D (2016) Insights on molecular mechanisms of chondrocytes death in osteoarthritis. Int J Mol Sci 17(12):2146

    Google Scholar 

  • Colnot C, Sidhu SS, Balmain N, Poirier F (2001) Uncoupling of chondrocyte death and vascular invasion in mouse galectin 3 null mutant bones. Dev Biol 229(1):203–214

    CAS  Google Scholar 

  • Dalvi PS, Wilder-Kofie T, Mares B, Dalvi RR, Billups LH (2002) Toxicologic implications of the metabolism of thiram, dimethyldithiocarbamate and carbon disulfide mediated by hepatic cytochrome p450 isozymes in rats. Pestic Biochem Physiol 74(2):85–90

    CAS  Google Scholar 

  • Eaton DL, de Sauvage FJ (1997) Thrombopoietin: the primary regulator of megakaryocytopoiesis and thrombopoiesis. Exp Hematol 25(1):1–7

    CAS  Google Scholar 

  • Edwards IR, Ferry DG, Temple WA (1991) Fungicides and related compounds. In: Hayes WJ, Laws ER, editors. Handbook of pesticide toxicology. New York: Academic.

  • Godoy P, Hewitt NJ, Albrecht U, Andersen ME, Ansari N, Bhattacharya S, Bode JG, Bolleyn J, Borner C, Böttger J, Braeuning A, Budinsky RA, Burkhardt B, Cameron NR, Camussi G, Cho CS, Choi YJ, Craig Rowlands J, Dahmen U, Damm G, Dirsch O, Donato MT, Dong J, Dooley S, Drasdo D, Eakins R, Ferreira KS, Fonsato V, Fraczek J, Gebhardt R, Gibson A, Glanemann M, Goldring CE, Gómez-Lechón MJ, Groothuis GM, Gustavsson L, Guyot C, Hallifax D, Hammad S, Hayward A, Häussinger D, Hellerbrand C, Hewitt P, Hoehme S, Holzhütter HG, Houston JB, Hrach J, Ito K, Jaeschke H, Keitel V, Kelm JM, Kevin Park B, Kordes C, Kullak-Ublick GA, LeCluyse E, Lu P, Luebke-Wheeler J, Lutz A, Maltman DJ, Matz-Soja M, McMullen P, Merfort I, Messner S, Meyer C, Mwinyi J, Naisbitt DJ, Nussler AK, Olinga P, Pampaloni F, Pi J, Pluta L, Przyborski SA, Ramachandran A, Rogiers V, Rowe C, Schelcher C, Schmich K, Schwarz M, Singh B, Stelzer EH, Stieger B, Stöber R, Sugiyama Y, Tetta C, Thasler WE, Vanhaecke T, Vinken M, Weiss TS, Widera A, Woods CG, Xu JJ, Yarborough KM, Hengstler JG (2013) Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol 87(8):1315–1530

    CAS  Google Scholar 

  • Gutiérrez AM, Montalti D, Reboredo GR, Salibián A, Catalá A (1998) Lindane distribution and fatty acid profiles of uropygial gland and liver of columba livia after pesticide treatment. Pestic Biochem Physiol 59(3):137–141

    Google Scholar 

  • Hayashi H, Beppu T, Shirabe K, Maehara Y, Baba H (2014) Management of thrombocytopenia due to liver cirrhosis: a review. World J Gastroenterol 20(10):2595–2605

    CAS  Google Scholar 

  • Hernández AF, Gil F, Lacasaña M, Rodríguezbarranco M, Tsatsakis AM, Requena M, Parrón T, Alarcón R (2013) Pesticide exposure and genetic variation in xenobiotic-metabolizing enzymes interact to induce biochemical liver damage. Food Chem Toxicol 61:144–151

    Google Scholar 

  • Huang SC, Rehman MU, Lan YF, Qiu G, Zhang H, Iqbal MK, Luo HQ, Mehmood K, Zhang LH, Li JK (2017a) Tibial dyschondroplasia is highly associated with suppression of tibial angiogenesis through regulating the hif-1ɑ/vegf/vegfr signaling pathway in chickens. Sci Rep 7(1):9089

    Google Scholar 

  • Huang S, Tong X, Rehman MU, Wang M, Zhang L, Wang L, Li J, Yang S (2017b) Oxygen supplementation ameliorates tibial development via stimulating vascularization in tibetan chickens at high altitudes. Int J Biol Sci 13(12):1547–1559

    CAS  Google Scholar 

  • Huang S, Zhang L, Rehman MU, Iqbal MK, Lan Y, Mehmood K, Zhang H, Qiu G, Nabi F, Yao W, Wang M, Li J (2017c) High altitude hypoxia as a factor that promotes tibial growth plate development in broiler chickens. PLoS One 12(3):e0173698

    Google Scholar 

  • Huang S, Kong A, Cao Q, Tong Z, Wang X (2019) The role of blood vessels in broiler chickens with tibial dyschondroplasia. Poult Sci. https://doi.org/10.3382/ps/pez497

    Google Scholar 

  • Kaushansky K (1995) Thrombopoietin the primary regulator of platelet production. Blood 86(2):419–431

    CAS  Google Scholar 

  • Kusumbe AP, Ramasamy SK, Adams RH (2014) Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507(7492):323–328

    CAS  Google Scholar 

  • Kuter DJ, Begley CG (2001) Recombinant human thrombopoietin: basic biology and evaluation of clinical studies. Blood 100(10):3457–3469

    Google Scholar 

  • Laine O, Joutsi-Korhonen L, Lassila R, Huhtala H, Vaheri A, Mäkelä S, Mustonen J (2016) Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection. Medicine 95(52):e5689

    CAS  Google Scholar 

  • Li JJ, Huang YQ, Basch R, Karpatkin S (2001) Thrombin induces the release of angiopoietin-1 from platelets. Thromb Haemost 85(2):204–206

    CAS  Google Scholar 

  • Li R, Hoffmeister KM, Falet H (2016) Glycans and the platelet life cycle. Platelets 27(6):505–511

    CAS  Google Scholar 

  • Liu H, Yang J, Huang S, Liu R, He Y, Zheng D, Liu C (2017) Mulberry crude extracts induce nrf2 activation and expression of detoxifying enzymes in rat liver: implication for its protection against np-induced toxic effects. J Funct Foods 32:367–374

    Google Scholar 

  • Lopez-Antia A, Ortiz-Santaliestra ME, Blas EG, Camarero PR, Mougeot F, Mateo R (2015) Adverse effects of thiram-treated seed ingestion on the reproductive performance and the offspring immune function of the red-legged partridge. Environ Toxicol Chem 34(6):1320–1329

    CAS  Google Scholar 

  • Matsuura S, Mi R, Koupenova M, Eliades A, Patterson S, Toselli P, Thon J, Italiano JE Jr, Trackman PC, Papadantonakis N, Ravid K (2016) Lysyl oxidase is associated with increased thrombosis and platelet reactivity. Blood 127(11):1493–1501

    CAS  Google Scholar 

  • Mishra VK, Srivastava MK, Raizada RB (1993) Testicular toxicity of thiram in rat: morphological and biochemical evaluations. Ind Health 31(2):59–67

    CAS  Google Scholar 

  • Molina-Ruiz JM, Cieslik E, Walkowska I (2015) Optimization of the quechers method for determination of pesticide residues in chicken liver samples by gas chromatography-mass spectrometry. Food Anal Method 8(4):898–906

    Google Scholar 

  • Ndoe MG, Herve A, Kamdje N, Ntungwen CF, Michel A, Nloga N (2015) Nutritional state impact on the liver detoxification function in patients infected by hiv under antiretroviral drugs at the bertoua day hospital of cameroon. J Dis Med Plant 1:37–41

    Google Scholar 

  • Peck-Radosavljevic M (2017) Thrombocytopenia in chronic liver disease. Liver Int 37(6):778–793

    Google Scholar 

  • Radomski JL, Deichmann WB, Clizer EE (1968) Pesticide concentrations in the liver, brain and adipose tissue of terminal hospital patients. Fd Cosmet Toxicol 6(2):209–220

    CAS  Google Scholar 

  • Ramasamy SK, Kusumbe AP, Wang L, Adams RH (2014) Endothelial notch activity promotes angiogenesis and osteogenesis in bone. Nature 507(7492):376–380

    CAS  Google Scholar 

  • Sancho E, Ferrando MD, Gamon M, Andreu-Moliner E (1998) Uptake and elimination kinetics of a pesticide in the liver of the european eel. J Environ Sci Health B 33(1):83–98

    CAS  Google Scholar 

  • Saqib TA, Naqvi SN, Siddiqui PA, Azmi MA (2005) Detection of pesticide residues in muscles, liver and fat of 3 species of labeo found in kalri and haleji lakes. J Environ Biol 26(2 Suppl):433–438

    CAS  Google Scholar 

  • Saran U, Piperni SG, Chatterjee S (2014) Role of angiogenesis in bone repair. Arch Biochem Biophys 561:109–117

    CAS  Google Scholar 

  • Shim MY, Karnuah AB, Anthony NB, Pesti GM, Aggrey SE (2012) The effects of broiler chicken growth rate on valgus, varus, and tibial dyschondroplasia. Poult Sci 91(1):62–65

    CAS  Google Scholar 

  • Siemensma NP, Bathal PS, Penington DG (1975) The effect of massive liver resection on platelet kinetics in the rat. J Lab Clin Med 86(5):817–833

    CAS  Google Scholar 

  • Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB (2013) Profiling 976 toxcast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol 26(6):878–895

    CAS  Google Scholar 

  • Sungaran R, Markovic B, Chong BH (1997) Localization and regulation of thrombopoietin mRNa expression in human kidney, liver, bone marrow, and spleen using in situ hybridization. Blood 89(1):101–107

    CAS  Google Scholar 

  • Svoboda O, Bartunek P (2015) Origins of the vertebrate erythro/megakaryocytic system. Biomed Res Int 2015:632171

    Google Scholar 

  • Verheul HM, Hoekman K, Luykx-De BS, Eekman CA, Folman CC, Broxterman HJ, Pinedo HM (1997) Platelet: transporter of vascular endothelial growth factor. Clin Cancer Res 3:2187–2190

    CAS  Google Scholar 

  • Wartiovaara U, Salven P, Mikkola H, Lassila R, Kaukonen J, Joukov V, Orpana A, Ristimäki A, Heikinheimo M, Joensuu H, Alitalo K, Palotie A (1998) Peripheral blood platelets express vegf-c and vegf which are released during platelet activation. Thromb Haemost 80(1):171–175

    CAS  Google Scholar 

  • Xin G, Wei Z, Ji C et al (2016) Metformin uniquely prevents thrombosis by inhibiting platelet activation and mtdna release. Sci Rep 6:36222

    CAS  Google Scholar 

  • Zhang H, Mehmood K, Jiang X, Yao W, Iqbal M, Waqas M, Rehman MU, Li A, Shen Y, Li J (2018) Effect of tetramethyl thiuram disulfide (thiram) in relation to tibial dyschondroplasia in chickens. Environ Sci Pollut R 25(28):28264–28274

    CAS  Google Scholar 

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Acknowledgments

The authors would like to thank the anonymous reviewers for their careful reading of our manuscript and helpful suggestions.

Funding

This work was supported by the National Key R&D Program of China (No. 2017YFD0502200) and the National Natural Science Foundation of China (No. 31460682).

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Authors and Affiliations

  1. College of Animals Husbandry and Veterinary Medicine, Tibet Agricultural and Animal Husbandry University, Nyingchi, 860000, Tibet, China

    Shu-Cheng Huang & Jia-kui Li

  2. College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China

    Lei Li, Mujeeb Ur Rehman, Jin-dong Gao, Li-hong Zhang, Xiao-le Tong, Muhammad Waqas & Jia-kui Li

  3. College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, 450002, China

    Shu-Cheng Huang

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  1. Shu-Cheng Huang
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Correspondence to Jia-kui Li.

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Huang, SC., Li, L., Rehman, M.U. et al. Tibial growth plate vascularization is inhibited by the dithiocarbamate pesticide thiram in chickens: potential relationship to peripheral platelet counts alteration. Environ Sci Pollut Res 26, 36322–36332 (2019). https://doi.org/10.1007/s11356-019-06664-z

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