, Volume 42, Issue 4, pp 258–264

Effects of Epiphyseal Proteins and Melatonin on Blood Biochemical Parameters of Fluoride-Intoxicated Rats


We examined the effects of fluoride intoxication on certain blood plasma biochemical indices in rats. Fortyeight adult female Wistar rats weighing 123-142 g were divided into eight groups: two control groups (0 and 28 days) and six experimental groups, namely sham-injected animals (vehicle), injected with pineal proteins (PP) and melatonin (Mel), intoxicated with fluoride (F), and also F+PP and F+Mel groups. Fluoride (150 ppm, per os administration with drinking water), melatonin (10 mg/kg, i.p.), and PP (100 μg/kg, i.p.) were administered daily for 28 days. Blood samples were collected at the end of experiments to estimate plasma [Na+] and [K+], alkaline phosphatase (ALP) activity, and levels of glucose and proteins in different animal groups. The plasma [K+] and [Na+], and ALP activity were significantly (P < 0.05) elevated in F-treated animals, as compared with others. Administration of PP and Mel in F-treated rats caused significant (P < < 0.05) reduction of [Na+], [K+], and ALP levels. Interestingly, PP and Mel administrations resulted in noticeable (P < 0.05) increases in the plasma glucose level in F-intoxicated animals, as compared to other groups. These findings convincingly indicate that PP and Mel exert ameliorative effects on fluoride-induced adverse changes in certain biochemical parameters in rats.


fluoride oxidative stress plasma biochemical composition melatonin pineal proteins alkaline phosphatase 


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  1. 1.
    R. J. Collier, D. K. Beede, W. W. Thatcher, et al., “Influences of environment and its modification on dairy animal health and production,” J. Dairy Sci., 65, 2213–2227 (1982).CrossRefPubMedGoogle Scholar
  2. 2.
    J. W. West, “Effects of heat stress on production of dairy cattle,” J. Dairy Sci., 86, 2131–2144 (2003).CrossRefPubMedGoogle Scholar
  3. 3.
    R. K. Ringer, “Effects on domestic animals,” in: Ecotoxicology and Climate, J. A. Bourdeau, W. K. Haines, and C. R. K. Murti (eds.), John Wiley and Sons Ltd. (1989), pp. 225–232.Google Scholar
  4. 4.
    V. K. Bharti, “Fluorosis: A serious health problem of domestic animals,” Livestock Int., 10, No. 12, 17–20 (2006).Google Scholar
  5. 5.
    R. Rzeuski, D. Chlubek, and Z. Machoy, “Interactions between fluoride and biological free-radical reactions,” Fluoride, 31, 43–45 (1998).Google Scholar
  6. 6.
    X. Y. Guo, G. F. Sun, and Y. C. Sun, “Oxidative stress from fluoride induced hepatotoxicity in rats,” Fluoride, 36, No. 1, 25–29 (2003).Google Scholar
  7. 7.
    S. L. Chawla, R. Yadav, D. Shah, and M. V. Rao, “Protective action of melatonin against fluoride-induced hepatotoxicity in adult female mice,” Fluoride, 41, No. 1, 44–51 (2008).Google Scholar
  8. 8.
    V. K. Bharti and R. S. Srivastava, “Fluoride-induced oxidative stress in rat’s brain and its amelioration by buffalo (Bubalus bubalis) pineal proteins and melatonin,” Biol. Trace Elem. Res., 130, No. 2, 131–140 (2009).CrossRefPubMedGoogle Scholar
  9. 9.
    P. Celi, A. D. Trana, and A. Quaranta, “Metabolic profile and oxidative status in goats during the peripartum period,” Aust. J. Exp. Agric., 48, No. 7, 1004–1008 (2008).CrossRefGoogle Scholar
  10. 10.
    W.H.O. Environmental Health Criteria, 36: Fluorine and Fluoride. WHO. Geneva. (1984).Google Scholar
  11. 11.
    C. Rodriguez, J. C. Mayo, R. M. Sainz, et al., “Regulation of antioxidant enzymes: a significant role for melatonin,” J. Pineal Res., 36, No. 1, 1–9 (2004).CrossRefPubMedGoogle Scholar
  12. 12.
    M. Diaz-Munoz, R. Hernandez-Munoz, J. Suarez, et al., “Day-night cycle of lipid peroxidation in rat cerebral cortex and their relationship to the glutathione cycle and superoxide dismutase activity,” Neuroscience, 16, 859–863 (1985).CrossRefPubMedGoogle Scholar
  13. 13.
    P. J. Mullenix, P. K. Denbesten, A. Schunior, and W. J. Kernan, “Neurotoxicity of sodium fluoride in rats,” Neurotoxicol. Teratol., 17, 169–177 (1995).CrossRefPubMedGoogle Scholar
  14. 14.
    M. L. Vani and K. P. Reddy, “Effects of fluoride accumulation on some enzymes of brain and gastrocnemius muscle of mice,” Fluoride, 33, 17–26 (2000).Google Scholar
  15. 15.
    H. J. Romijn, “The pineal: a tranquillizing organ,” Life Sci., 23, 2257–2274 (1978).CrossRefPubMedGoogle Scholar
  16. 16.
    P. Voisin, M. G. Harrington, J. L. Weller, et al., “Noradrenergic control of the synthesis of two rat pineal proteins,” Brain Res., 517, Nos. 1/2, 25–34 (1990).CrossRefPubMedGoogle Scholar
  17. 17.
    R. J. Reiter, D. Melchiorri, E. Sewerynek, and B. Poeggler, “A review of the evidence supporting melatonin’s role as an antioxidant,” J. Pineal Res., 23, 43–50 (1995).Google Scholar
  18. 18.
    R. J. Reiter, “Pineal melatonin: cell biology of its synthesis and of its physiological interactions,” Endocrinol. Rev., 12, 151–180 (1991).CrossRefGoogle Scholar
  19. 19.
    D. E. Blask, M. K. Vaughan, and R. J. Reiter, in: The Pineal Gland, R. Relkin (ed.), Elsevier, Amsterdam (1983), pp. 201–224.Google Scholar
  20. 20.
    M. Tandon, R. S. Srivastava, S. K. Meur, and M. Saini, “Proteins and peptides present in pineal gland and other brain structures of buffaloes,” Indian J. Animal Sci., 76 (5), 383–394 (2006).Google Scholar
  21. 21.
    V. Sejian, Studies on Pineal-Adrenal Relationship in Goats (Capra hircus) Under Thermal Stress, Ph.D. Thesis, Indian Veterinary Research Institute, Izatnagar, India (2006).Google Scholar
  22. 22.
    V. K. Bharti and R. S. Srivastava “Pineal proteins up-regulate specific antioxidant defense systems in the brain,” Oxid. Med. Cell. Longev., 2, No. 2, 88–92 (2009).CrossRefPubMedGoogle Scholar
  23. 23.
    V. K. Bharti and R. S. Srivastava, “Protective role of pineal proteins at different dose level on fluoride-induced changes in plasma biochemicals and blood antioxidants enzymes in rats,” Biol. Trace Elem. Res., DOI: 10.1007/s12011-010-8733-y (2010).
  24. 24.
    B. L. Oser, Hawk’s Physiological Chemistry, McGraw-Hill Book Co., New York (1965).Google Scholar
  25. 25.
    J. A. Varner, K. F. Jenson, W. Horvath, and R. L. Isaacson, “Chronic administration of aluminum fluoride or sodium fluoride to rats in drinking water: alteration in neuronal and cerebrovascular integrity,” Brain Res., 784, 284–298 (1998).CrossRefPubMedGoogle Scholar
  26. 26.
    V. K. Bharti, M. Gupta, and D. Lall, “Ameliorative effects of boron on serum profile in buffalo (Bubalus bubalis) fed a high fluoride ration,” Trop. Anim. Health Prod., 40, No. 2, 111–116 (2008).CrossRefPubMedGoogle Scholar
  27. 27.
    R. J. Verma and D. M. Guna Sherlin, “Sodium fluorideinduced hypoproteinemia and hypoglycemia in parental and F (1)-generation rats and amelioration by vitamins,” Food Chem. Toxicol., 40, No. 12, 1781–1788 (2002).CrossRefPubMedGoogle Scholar
  28. 28.
    L. I. Ding, “The nervous systemic complications of chronic fluorosis,” Chin. J. Endemiol., 2, 97–98 (1983).Google Scholar
  29. 29.
    J. A. Luke, The Effect of Fluoride on the Physiology of the Pineal Gland, Ph.D. Thesis, School of Biological Sciences, University of Surrey, England (1997).Google Scholar
  30. 30.
    D. Shanthakumari, S. Srinivasalu, and S. Subramanian, “Effects of fluoride intoxication on lipid peroxidation and antioxidant status in experimental rats,” Toxicology, 204, 219–228 (2004).CrossRefPubMedGoogle Scholar
  31. 31.
    S. M. Farley, J. E. Wrgedal, L. Smith, et al., “Fluoride therapy for osteoporosis: Characterization of the skeletal response by serial measurement of serum alkaline phosphatase activity,” Metabolism, 36, 211–218 (1987).CrossRefPubMedGoogle Scholar
  32. 32.
    S. P. S. Teotia and M. Teotia, “Endemic fluoride: bone and teeth-update,” Indian J. Environ. Toxicol., 1, 1 (1991).Google Scholar
  33. 33.
    V. Menon, M. Ram, J. Dorn, et al., “Oxidative stress and glucose levels in a population-based sample,” Diabetic Med., 21, 1346–1352 (2004).CrossRefPubMedGoogle Scholar
  34. 34.
    B. Benson and I. Ebels, “Pineal peptides,” J. Neural Transm., Suppl., 13, 157–173 (1978).Google Scholar
  35. 35.
    B. Bojková, M. Marková, E. Ahlersová, et al., “Metabolic effects of prolonged melatonin administration and shortterm fasting in laboratory rats,” Acta Vet. Brno, 75, 21–32 (2006).CrossRefGoogle Scholar
  36. 36.
    M. Ogeturk, I. Kus, A. Kavakli, et al., “Effects of melatonin on carbon tetrachloride-induced changes in rat serum,” J. Physiol. Biochem., 60, 205–210 (2004).CrossRefPubMedGoogle Scholar
  37. 37.
    V. Sejian and R. S. Srivastava, “Effects of melatonin on adrenal cortical functions of Indian goats under thermal stress,” Vet. Med. Int., 2010, 1–6. DOI:10.4061/2010/348919 (2010).CrossRefGoogle Scholar
  38. 38.
    M. Ramasamy, Studies on Bubaline Pineal Proteins/Peptides below 20 kDa and Their Immunopotentiation in Guinea Pigs, Ph.D. Thesis, Indian Veterinary Research Institute, Izatnagar, India (2006).Google Scholar
  39. 39.
    D. Swarup, S. Dey, S. R. C. Patra, et al., “Clinicoepidemiological observations of industrial bovine fluorosis in India,” Indian J. Anim. Sci., 71, 1111–1115 (2001).Google Scholar
  40. 40.
    D. Chlubek, H. E. Grucka, R. Polaniak, et al., “Activity of pancreatic antioxidant enzymes and malondialdehyde concentrations in rats with hyperglycemia caused by fluoride intoxication,” J. Trace Element Med. Biol., 17, No. 1, 57–60 (2003).CrossRefGoogle Scholar
  41. 41.
    V. K. Bharti, M. Gupta, D. Lall, and V. Kapoor, “Effect of boron on haemogram and biochemical profile of urine in buffalo calves fed a high fluoride ration,” Fluoride, 40, No. 4, 238–243 (2007).Google Scholar
  42. 42.
    A. K. Susheela, “Fluorosis management programme in India,” Curr. Sci., 77, No. 10, 1050–1056 (1999).Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2011

Authors and Affiliations

  1. 1.Indian Veterinary Research InstituteIzatnagarIndia
  2. 2.Nutrition and Toxicology Laboratory, Defence Institute of High Altitude Research (DIHAR)DRDO, Ministry of DefenceLehIndia

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