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Effect of Excess Fluoride Exposure on Radiographic and Histopathological Changes in Long Bones of Rabbit

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Abstract

The present study aimed to investigate the effects of excess fluoride exposure on long bones in young rabbits (Oryctolagus cuniculus). New Zealand White rabbits (n = 30) were randomly divided into five equal groups and were provided drinking water containing 0, 50, 100, 200, and 400 µg added fluoride per ml ad lib for a period of 90 days. Blood samples were collected on days 0, 45, and 90 of the experiment, and femur samples were collected for fluoride estimation on day 90 after radiography of long bone before sacrifice. Study revealed significant increase in serum fluoride concentration following oral intake of excess fluoride. Alterations in activities of alkaline phosphatase, aspartate transaminase, alanine transaminase, and concentrations of creatinine and urea nitrogen in blood plasma were also recorded in animals receiving excess fluoride, though changes revealed inconsistent pattern. Radiographic changes in long bones in fluoride exposed rabbits included widening of metaphysis, thinning of cortical region, and a variety of osteopenic changes like osteoporosis and osteomalacia that were more prominent in animals receiving 200 ppm or more than 200 ppm fluoride in drinking water. Important changes in histomorphology of growth plate in long bones recorded in excess fluoride (> 100 ppm) exposed rabbits included irregular thickening of epiphyseal growth plate with haphazard orientation of chondrocytes forming nodular protrusion into metaphysis. Fluoride exposure induced both osteogenesis and osteoporosis to a degree varying with dose of fluoride exposure.

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References

  1. Ranjan R, Swarup D, Patra RC (2009) Oxidative stress indices in erythrocytes, liver and kidneys of fluoride-exposed rabbits. Fluoride 42:83–88

    Google Scholar 

  2. Boivin G, Chavassieux P, Chapuy MC, Baud CA, Meunier PJ (1989) Skeletal fluorosis: histomorphometric analysis of bone changes and bone fluoride content in 29 patients. Bone 10:89–99. https://doi.org/10.1016/8756-3282(89)90004-5

    Article  CAS  PubMed  Google Scholar 

  3. Khandare AL, Suresh P, Kumar PU, Lakshmaiah N, Manjula N, Rao GS (2005) Beneficial effect of copper supplementation on deposition of fluoride in bone in fluoride and molybdenum fed rabbits. Calcif Tissue Int 77:233–238. https://doi.org/10.1007/s00223-005-0071-2

    Article  CAS  PubMed  Google Scholar 

  4. Jiang N, Guo F, Xu W, Xhang Z, Jin H, Shi L, Zhang X, Gao J, Xu H (2020) Effect of fluoride on osteocyte-driven osteoclastic differentiation. Toxicol 436:152429. https://doi.org/10.1016/j.tox.2020.152429

    Article  CAS  Google Scholar 

  5. Ranjan R, Ranjan A (2015) Fluoride Toxicity in Animals. Springer International Publishing AG Switzerland. ISBN 798–3–319–175H-9 PPI-105

  6. Turkekul R, Arihan SK, Yildirim S, Arihan O, Oto G, Ekin S, Yildiz D (2019) Effect of acute and chronic fluoride administration on bone histopathology, bone fluoride accumulation, and locomotor activity in an animal model of paleopathological fluorosis. Fluoride 53:77–89

    Google Scholar 

  7. Kant V, Verma PK, Pankaj NK, Raina R (2009) Experimental osteo-fluorosis in goats of Jammu and Kashmir. Vet Scan 4(2):45

    Google Scholar 

  8. Yesildag A, Heybeli N, Candir O, Oyar O, Baykal B, Mumcu EF, Gulsoy UK (2004) Effects of fluoride on growth plate cartilage in rats: radiological and histopathological findings. Fluoride 37:221–230

    CAS  Google Scholar 

  9. Kurtul I, Atalgin H, Bozkurt EU (2007) Postnatal osteological development of the cervical vertebrae in the New Zealand White Rabbit. Vet Res Commun 31:643–651. https://doi.org/10.1007/s11259-007-3474-x

    Article  CAS  PubMed  Google Scholar 

  10. WHO (1984) Fluorine and Fluorides. Environmental Health Criteria 36. World Health Organization, Geneva

  11. Mikaelian I, Qualls-Jr CW, Guise SD, Whaley MW, Martineau D (1999) Bone fluoride concentrations in Beluga whales from Canada. J Wildl Dis 35:356–360. https://doi.org/10.7589/0090-3558-35.2.356

    Article  CAS  PubMed  Google Scholar 

  12. Kardinaal AF, Hoorneman G, Vaananen K, Charles P, Ando S, Maggiolini M, Charzewska J, Rotily M, Deloraine A, Heikkinen J, Juvin R, Schaafsma G (2000) Determinants of bone mass and bone geometry in adolescent and young adult women. Calcif Tissue Int 66:81–89. https://doi.org/10.1007/pl00005834

    Article  CAS  PubMed  Google Scholar 

  13. Culling CFA (1974) Handbook of histopathological and histochemical techniques (including museum techniques), 3rd edn. Butterworths, London

    Google Scholar 

  14. Snedecor GW, Cocharan WG (1994) Statistical methods, 8th edn. Iowa State University Press, Ames, Iowa

    Google Scholar 

  15. Isaksson H, Harjula T, Koistinen A, Ivarinen J, Seppanen K, Arokoski JPA, Jurvelin JS, Helminen HJ (2010) Collagen and mineral deposition in rabbit cortical bone during maturation and growth: effects on tissue properties. J Orthop Res 28:1626–1633. https://doi.org/10.1002/jor.21186

    Article  CAS  PubMed  Google Scholar 

  16. WHO (2002) Fluorides. Environmental Health Criteria 227. World Health Organization, Geneva

  17. She YX, Gesang DZ, Tian FY, Suo LZ, She YX, Gesang DZ, Tain FY, Suo LZ (2002) Analysis of fluorine concentration in rabbit blood and trace elements in its muscles. Chin J Anim Quar 19:23–24

    Google Scholar 

  18. Reddy GB, Khandare AL, Reddy PY, Rao GS, Balakrishna N, Srivalli I (2003) Antioxidant defense system and lipid peroxidation in patients with skeletal fluorosis and in fluoride intoxicated rabbits. Toxicol Sci 72:363–368. https://doi.org/10.1093/toxsci/kfg030

    Article  CAS  PubMed  Google Scholar 

  19. Chlubek D (2003) Fluoride and oxidative stress (Editorial Review). Fluoride 36:217–228

    CAS  Google Scholar 

  20. Bouaziz H, Ammar E, Ghorbel H, Ketala S, Jamoussi K, Ayadi F, Guermazi F, Zeghal N (2004) Effect of fluoride ingested by lactating mice on the thyroid function and bone maturation of their suckling pups. Fluoride 37:133–142

    CAS  Google Scholar 

  21. Singh PK, Sahoo N, Ray SK (2002) Clinico-pathological features of fluorosis in goats. Indian Vet J 79:776–779

    Google Scholar 

  22. Kapoor V, Prasad T, Bhatia KC (1993) Effect of dietary fluoride on histopathological changes in calves. Fluoride 26:105–110

    CAS  Google Scholar 

  23. Upadhyay SR, Roy S, Pandey PK, Mishra N, Roy M, Nair S, Bhui A, Yadav S (2005) Studies on haemato-biochemical changes during bovine fluorosis. Indian J Vet Med 25:19–23

    Google Scholar 

  24. Sahoo N, Singh PK, Ray SK, Bisoi PC, Mahapatra HK (2003) Fluorosis in sheep around an aluminium factory. Indian Vet J 80:617–621

    Google Scholar 

  25. Patra RC, Dwivedi SK, Bhardwaj B, Swarup D (2000) Industrial fluorosis in cattle and buffalo around Udaipur, India. Sci Total Environ 253:145–150. https://doi.org/10.1016/s0048-9697(00)00426-5

    Article  CAS  PubMed  Google Scholar 

  26. Maiti SK, Das PK (2004) Biochemical changes in endemic dental fluorosis in cattle. Indian J Anim Sci 74:169–171

    CAS  Google Scholar 

  27. Shivashankara AR, Shankara YMS, Rao SH, Bhat PG (2000) A clinical and biochemical study of chronic fluoride toxicity in children of Keru Thanda of Gulbarga district, Karnataka, India. Fluoride 33:66–73

    CAS  Google Scholar 

  28. Shashi A (2003) In vivo studies concerning toxic effects of sodium fluoride on hepatic function in rabbits. Fluoride 36:30–37

    CAS  Google Scholar 

  29. Shashi A, Thapar SP (2000) Histopathology of fluoride-induced hepatotoxicity in rabbits. Fluoride 34:34–42

    Google Scholar 

  30. Akdogan M, Bilgili A, Karoz E, Gokcimen A, Eraslan G, Ustuner E (2002) The structural and biochemical changes of kidney tissue on fluorosis in rabbits. Turk J Vet Anim Sci 26:71–77

    Google Scholar 

  31. Birkner E, Grucka-Mamczar E, Zwirska-Korczala K, Zalejska-Fiolka J, Stawiarska-Pieta B, Kasperczyk S, Kasperczyk A (2006) Influence of sodium fluoride and caffeine on the kidney function and free-radical processes in that organ in adult rats. Biol Trace Elem Res 109:35–48

    Article  CAS  PubMed  Google Scholar 

  32. Szkoda J, Juszkiewicz T (1991) Fluorine distribution in tissues following multiple administration of sodium fluoride in rabbits. Medycyna-Weberynaryjna 47:27–28

    Google Scholar 

  33. Roholm K (1937) Fluoride intoxication: A clinical-hygienic study with a review of the literature and some experimental investigations. London. H.K. Lewis and Co., Ltd, pp 141–143

    Google Scholar 

  34. Wang Y, Yin Y, Gilula LA, Wilson AJ (1994) Endemic fluorosis of the skeleton: Radiographic features in 127 patients. AJR Am J Roentgenol 162:93–98. https://doi.org/10.2214/ajr.162.1.8273699

    Article  CAS  PubMed  Google Scholar 

  35. Xu JC, Wang YZ, Xue DM, Xin SZ, Dai RT, Zhang ZL, Cheng X (1987) X-ray findings and pathological basis of bone fluorosis. Chin Med J 100:8–16

    CAS  PubMed  Google Scholar 

  36. Christie DP (1980) The spectrum of radiographic bone changes in children with fluorosis. Radiology 136:85–90. https://doi.org/10.1148/radiology.136.1.7384528

    Article  CAS  PubMed  Google Scholar 

  37. Zong CL, Wu EH (1986) Osteoporosis: an early radiographic sign of endemic fluorosis. Skeletal Radiol 15:350–353. https://doi.org/10.1007/BF00348860

    Article  Google Scholar 

  38. Soriano M (1968) Periostitis deformans due to wine fluorosis. Fluoride 1:56–64

    Google Scholar 

  39. Susheela AK, Mukherjee D (1981) Fluoride poisoning and the effect on collagen biosynthesis of osseus and non-osseous tissues of rabbit. Toxicol Eur Res 3:99–104

    CAS  PubMed  Google Scholar 

  40. Yan X, Hao X, Nie Q, Feng C, Wang H, Sun Z, Niu R, Wang J (2015) Effects of fluoride on the ultrastructure and expression of Type I collagen in rat hard tissue. Chemosphere 128:36–41. https://doi.org/10.1016/j.chemosphere.2014.12.090

    Article  CAS  PubMed  Google Scholar 

  41. Jiang N, Guo F, Sun B, Zhang X, Xu H (2020) Different effects of fluoride exposure on the three major bone cell types. Biol Trace Elem Res 193:226–233. https://doi.org/10.1007/s12011-019-01684-9

    Article  CAS  PubMed  Google Scholar 

  42. Schultz M, Kierdorf U, Sedlacek F, Kierdorf H (1998) Pathological bone changes in the mandibles of wild red deer (Cervus elaphus L.) exposed to high environmental levels of fluoride. J Anat 193:431–442. https://doi.org/10.1046/j.1469-7580.1998.19330431.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are thankful to the Director, ICAR-Indian Veterinary Research Institute, Izatnagar, for providing the required necessary facilities.

Funding

The authors received research funding from the Director, ICAR-Indian Veterinary Research Institute, Izatnagar.

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Authors and Affiliations

  1. ICAR-Indian Veterinary Research Institute, Izatnagar, 243122, U.P., India

    Rakesh Ranjan, Devendra Swarup, Anil Kumar Sharma & Hari Prasad Aithal

  2. Department of Veterinary Pharmacology and Toxicology, College of Veterinary and Animal Sciences, RAJUVAS, Bikaner, 334001, Rajasthan, India

    Amita Ranjan

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  1. Rakesh Ranjan
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Contributions

RR and DS contributed to the study conception and design. AKS and HPA performed histopathology and radiography. Data analysis and interpretation were performed by RR, AKS, HPA, and AR. The first draft of the manuscript was written by RR, and AR revised it critically and updated references. All authors read and approved the final manuscript.

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Correspondence to Amita Ranjan.

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Ranjan, R., Swarup, D., Sharma, A.K. et al. Effect of Excess Fluoride Exposure on Radiographic and Histopathological Changes in Long Bones of Rabbit. Biol Trace Elem Res 202, 990–1000 (2024). https://doi.org/10.1007/s12011-023-03740-x

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  • DOI: https://doi.org/10.1007/s12011-023-03740-x

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