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Effect of tetramethyl thiuram disulfide (thiram) in relation to tibial dyschondroplasia in chickens

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Abstract

Tetramethyl thiuram disulfide (thiram) is one of the important pesticides, which is extensively used in agriculture, but if it is combined with the cell membrane, then it causes membrane damage, bone morphogenic inactivation, and inhibited angiogenesis. Thiram has been considered a common cause of tibial dyschondrolplasia (TD) in various avian species, because it becomes the part of feed due to environmental contamination and its overuse in agriculture as pesticides or fungicide. However, there is no systematic study on the changes of the correlation indexes with toxic effect of the thiram in chickens. Therefore, we evaluated the toxic effects of thiram on growth performance of chickens, viscera organ index, pathological changes in tissue, and gene expression associated with osteoblast differentiation, vascularization, and tibial bone development. For this study, 1-day chickens (n = 300) were randomly distributed into two equal groups, control group (normal basal diet) and thiram group (adding thiram 40 mg/kg in basal diet). The result presented that thiram group chickens were looking unhealthy, lazy, and showing clinical symptoms like lameness. Thiram treatment significantly reduced the performance of chickens, liver index, and tibial length compared with control group. The toxic effect of thiram increased the visceral organ index (spleen and cardiac), tibia index, and TD severity considerably. It also increased serum Ca2+ and P3+ concentration and decreased tibial density compared to control chickens but the difference was not significant. Histopathology of tibia and liver showed that there were severe lesions due to toxic effect of thiram. Furthermore, HIF-1α and VEGF antibody localizations were increased and WNT4 localization was reduced significantly in immunohistochemical analysis. This systemic study of toxic effects of thiram in chicken concluded that thiram reduced the growth performance of chickens through decreasing liver index, whereas increasing kidney, cardiac, and spleen index, and induced TD by changing the expressions of VEGF, HIF-1α, and WNT4.

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References

  • Andres JA, Correa NS, Rosas SB (1997) Survival and symbiotic properties of Bradyrhizobium japonicum in the presence of thiram: isolation of fungicide resistant strains. Biol Fertil Soils 26(2):141–145

    Article  Google Scholar 

  • Araldi E, Schipani E (2010) Hypoxia, HIFs and bone development. Bone 47:190–196

    Article  CAS  Google Scholar 

  • Beckmann R, Houben A, Tohidnezhad M, Kweider N, Fragoulis A, Wruck CJ, Brandenburg LO, Hermanns-Sachweh B, Goldring MB, Pufe T, Jahr H (2014) Mechanical forces induce changes in VEGF and VEGFR-1/sFlt-1 expression in human chondrocytes. Int J Mol Sci 15(9):5456–15474

    Article  CAS  Google Scholar 

  • Bencko V, Foong FYL (2017) The history of organic arsenical pesticides and health risks related to the use of agent blue. Ann Agric Environ Med 24(2):312–316

    Article  Google Scholar 

  • Bo Y, Jia C, Liu Y, Li J, Kevork K, Alhezaimi K et al (2014) Wnt4 signaling prevents skeletal aging and inflammation by inhibiting nuclear factor-κB. Nat Med 20(9):1009–1017

    Article  CAS  Google Scholar 

  • Bose S, Tarafder S, Bandyopadhyay A (2016) Effect of chemistry on osteogenesis and angiogenesis towards bone tissue engineering using 3d printed scaffolds. Ann Biomed Eng:1–12

  • Dan H, Simsa-Maziel S, Reich A, Sela-Donenfeld D, Monsonego-Ornan E (2012) The role of matrix gla protein in ossification and recovery of the avian growth plate. Front Endocrinol 3:79

    Article  Google Scholar 

  • Genin O, Hasdai A, Shinder D, Pines M (2012) The effect of inhibition of heat-shock proteins on thiram-induced tibial dyschondroplasia. Poult Sci 91:1619–1626

    Article  CAS  Google Scholar 

  • Houshmand M, Azhar K, Zulkifli I, Bejo MH, Meimandipour A, Kamyab A (2011) Effects of non-antibiotic feed additives on performance, tibial dyschondroplasia incidence and tibia characteristics of broilers fed low-calcium diets. J Anim Physiol Anim Nutr 95(3):351–358

    Article  CAS  Google Scholar 

  • Hudson RH, Tucker RK, Haegele MA (1984) Handbook of toxicity of pesticides to wildlife, Resource publication 153. US Department of the Interior, Fish and Wildlife Service, Washington DC

    Google Scholar 

  • Iqbal MK, Liu J, Nabi F, Rehman MU, Zhang H, Tahir AH, Li J (2016) Recovery of chicken growth plate by heat-shock protein 90 inhibitors epigallocatechin-3-gallate and apigenin in thiram-induced tibial dyschondroplasia. Avian Dis 60:773–778

    Article  Google Scholar 

  • Jr LR, Monsonego-Ornan E (2007) Tibial dyschondroplasia 40 years later. Poult Sci 86(10):2053–2058

    Article  Google Scholar 

  • Kaukonen E, Norring M, Valros A (2016) Perches and elevated platforms in commercial broiler farms: use and effect on walking ability, incidence of tibial dyschondroplasia and bone mineral content. Animal 11(5):864–871

    Article  CAS  Google Scholar 

  • Khan SH, Shahid R, Mian AA, Sardar R, Anjum MA (2010) Effect of the level of cholecalciferol supplementation of broiler diets on the performance and tibial dyschondroplasia. J Anim Physiol Anim Nutr 94(5):584–593

    Article  CAS  Google Scholar 

  • Kronenberg HM (2003) Developmental regulation of the growth plate. Nature 423:332–336

    Article  CAS  Google Scholar 

  • Kunkur VK, Hunje R, Biradar Patil NK, Vyakarnhal BS (2007) Effect of seed coating with polymer, fungicide and insecticide on seed quality in cotton during storage. Karnataka J Agric Sci 20(1):137–139

    Google Scholar 

  • Li J, Bi D, Pan S, Zhang Y (2007) Effect of diet with thiram on liver antioxidant capacity and tibial dyschondroplasia in broilers. Br Poult Sci 48(6):724–728

    Article  CAS  Google Scholar 

  • Liu H, Yao G, Liu X, Liu C, Zhan J, Liu D, Wang P, Zhou Z (2017) Approach for pesticide residue analysis for metabolite prothioconazole-desthio in animal origin food. J Agric Food Chem 65(11):2481–2487

    Article  CAS  Google Scholar 

  • Lopezantia A, Ortizsantaliestra ME, Garcíade BE, 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

    Article  CAS  Google Scholar 

  • Me GDES, Marrama L, Ndiaye K, Coly M, Faye O (2002) Investigation of deaths in an area of groundnut plantations in casamance, south of Senegal after exposure to carbofuran, thiram and benomyl. J Expo Anal Environ Epidemiol 12(5):381

    Article  CAS  Google Scholar 

  • Mehmood K, Zhang H, Iqbal MK, Rehman MU, Shahzad M, Li K, Huang S, Nabi F, Zhang L, Li J (2017) In vitro effect of Apigenin and Danshen in Tibial dyschondroplasia through inhibition of Hsp90 and VEGF expressions in avian growth plate cells. Avian Dis 61(3):372–377

    Article  Google Scholar 

  • Mehmood K, Zhang H, Iqbal MK, Rehman MU, Li K, Huang S, Shahzad M, Nabi F, Iqbal M, Li J (2018a) Tetramethylpyrazine mitigates toxicity and liver oxidative stress in tibial dyschondroplasia chickens. Pak Vet J 38:76–80

    Article  Google Scholar 

  • Mehmood K, Zhang H, Li K, Wang L, Rehman MU, Nabi F, Iqbal MK, Luo H, Shahzad M, Li J (2018b) Effect of tetramethylpyrazine on tibial dyschondroplasia incidence, tibial angiogenesis, performance and characteristics via HIF-1α/VEGF signaling pathway in chickens. Sci Rep 8:2495

    Article  CAS  Google Scholar 

  • Nabi F, Li K, Shahzad M et al (2016a) Gambogic acid inhibits Hsp90 expressions in thiram-induced tibial dyschondroplasia. Pak Vet J 36:224–226

    CAS  Google Scholar 

  • Nabi F, Shahzad M, Liu J, Li K, Han Z, Zhang D, Iqbal MK, Li J (2016b) Hsp90 inhibitor celastrol reinstates growth plate angiogenesis in thiram-induced tibial dyschondroplasia. Avian Pathol 45:187–193

    Article  CAS  Google Scholar 

  • National Research Council (NRC) (2001) Nutrient requirements of poultry, 9th edn. National Academy Press, Washington DC

    Google Scholar 

  • Orth MW, Cook ME (1994) Avian tibial dyschondroplasia: a morphological and biochemical review of the growth plate lesion and its causes. Vet Pathol 31:403–414

    Article  CAS  Google Scholar 

  • Oruc HH (2009) Fungicides and their effects on animals. J Vet Diagn Investig 17:349–362

    Google Scholar 

  • Osman AG, Sherif AM, Elhussein AA, Mohamed AT (2012) Sensitivity of some nitrogen fixers and the target pest fusarium oxysporum to fungicide thiram. Interdiscip Toxicol 5(1):25

    Article  CAS  Google Scholar 

  • Paliwal A, Gurjar RK, Sharma HN (2009) Analysis of liver enzymes in albino rat under stress of λ-cyhalothrin and nuvan toxicity. Biol Med 1(2):70–73

    CAS  Google Scholar 

  • Palumbi SR (2001) Humans as the world's greatest evolutionary force. Science 293(5536):1786–1790

    Article  CAS  Google Scholar 

  • Philippart C, Tzehoval E, Moricard Y, Bringuier AF, Seebold C, Lemoine FM, Arys A, Dourov N, Labat ML (1993) Immune cell defects affect bone remodelling in osteopetrotic op/op mice. Bone Miner 23(3):317–332

    Article  CAS  Google Scholar 

  • Portoles T, Ibáñez M, Garlito B, Nácher-Mestre J, Karalazos V, Silva J et al (2017) Comprehensive strategy for pesticide residue analysis through the production cycle of gilthead sea bream and Atlantic salmon. Chemosphere 179:242–253

    Article  CAS  Google Scholar 

  • Rasul AR, Howell JM (1974) The toxicity of some dithiocarbamate compounds in young and adult domestic fowl. Toxicol Appl Pharmacol 30:63–78

    Article  CAS  Google Scholar 

  • Rath NC, Huff WE, Balog JM, Huff GR (2004) Comparative efficacy of different dithiocarbamates to induce tibial dyschondroplasia in poultry. Poult Sci 83:266–274

    Article  CAS  Google Scholar 

  • Rath NC, Huff WE, Huff GR (2007) Thiram-induced changes in the expression of genes relating to vascularization and tibial dyschondroplasia. Poult Sci 86:2390–2395

    Article  CAS  Google Scholar 

  • Rolle VL, Richard PY, Carrault G (2008) An autonomic nervous system model applied to the analysis of orthostatic tests. Model Simul Eng 2008:2

    Google Scholar 

  • Saeki S (1957) Studies on the influences of steroid hormones upon the cellular blood elements and blood-forming organs of the rats. Folia Endocrinologica Japonica 33(8):701–720

    Article  Google Scholar 

  • Simsa S, Hasdai A, Dan H, Ornan EM (2007) Induction of tibial dyschondroplasia in turkeys by tetramethylthiuram disulfide (thiram). Poult Sci 86(8):1766–1771

    Article  CAS  Google Scholar 

  • Tian WX, Li J, Qin P, Wang R, Ning GB, Qiao JG, Li HQ, Bi DR, Pan SY, Guo DZ (2013) Screening of differentially expressed genes in the growth plate of broiler chickens with tibial dyschondroplasia by microarray analysis. BMC Genomics 14:276

    Article  CAS  Google Scholar 

  • Velada I, Capela-Silva F, Reis F, Pires E, Egas C, Rodrigues-Santos P, Barros MT (2011) Expression of genes encoding extracellular matrix macromolecules and metalloproteinases in avian tibialdyschondroplasia. J Comp Pathol 145:174–186. https://doi.org/10.1016/j.jcpa.2010.12.008

    Article  CAS  Google Scholar 

  • Walia S, Sharma RK, Parmar BS (2009) Isolation and simultaneous lc analysis of thiram and its less toxic transformation product in ds formulation. Bull Environ Contam Toxicol 83(3):363–368

    Article  CAS  Google Scholar 

  • Weppelman RM, Long RA, van Iderstine A, Taylor JE, Tolman RL, Peterson L, Olson G (1980) Antifertility effects of dithiocarbamates in laying hens. Biol Reprod 23:40–46

    Article  CAS  Google Scholar 

  • Yang BH, Lei RH, Wu CQ (2009) Oxidative damage in livers and kidneys induced by nano-copper particles in rats. J Environ Health:411–413

  • Zhang JP, Deng YF, Zhou ZL, Hou JF (2013) Expression and identification of recombinant chicken vascular endothelial growth factor in Pichia pastoris and its role in the pathogenesis of tibial dyschondroplasia. Poult Sci 92:3214–3227

    Article  CAS  Google Scholar 

  • Zhang H, Mehmood K, Li K, Rehman MU, Jiang X, Huang S, Wang L, Zhang L, Tong X, Nabi F, Yao W, Iqbal MK, Shahzad M, Li J (2018a) Icariin ameliorate thiram-induced tibial dyschondroplasia via regulation of WNT4 and VEGF expression in broiler chickens. Front Pharmacol 9:123

    Article  Google Scholar 

  • Zhang H, Mehmood K, Jiang X, Yao W, Iqbal M, Li K, Tong X, Wang L, Wang M, Zhang L, Nabi F, Rehman MU, Li J (2018b) Effect of icariin on Tibial dyschondroplasia incidence and Tibial characteristics by regulating P2RX7 in chickens. Biomed Res Int 2018:6796271

    Google Scholar 

  • Zhang H, Chang Z, Mehmood K, Rao ZA, Nabi F, Rehman MU et al (2018c) Nano copper induces apoptosis in pk-15 cells via a mitochondria-mediated pathway. Biol Trace Elem Res 181(1):62–70

    Article  CAS  Google Scholar 

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Funding

The study was supported by the National Key R&D Program of China (Project No. 2017YFD0502200) and supported by the Fundamental Research Funds for the Central Universities (No. 2662017QD015).

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  1. Hui Zhang and Khalid Mehmood contributed equally to this work.

Authors and Affiliations

  1. College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China

    Hui Zhang, Khalid Mehmood, Xiong Jiang, Wangyuan Yao, Mujahid Iqbal, Muhammad Waqas, Mujeeb Ur Rehman, Aoyun Li, Yaoqin Shen & Jiakui Li

  2. University College of Veterinary and Animal Sciences, Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan

    Khalid Mehmood

  3. College of Animals Husbandry and Veterinary Medicine, Tibet Agricultural and Animal Husbandry University, Linzhi, Tibet, 860000, People’s Republic of China

    Jiakui Li

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  1. Hui Zhang
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Correspondence to Jiakui Li.

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Zhang, H., Mehmood, K., Jiang, X. et al. Effect of tetramethyl thiuram disulfide (thiram) in relation to tibial dyschondroplasia in chickens. Environ Sci Pollut Res 25, 28264–28274 (2018). https://doi.org/10.1007/s11356-018-2824-2

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