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Silymarin and quercetin abrogates fluoride induced oxidative stress and toxic effects in rats

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Abstract

Flavonoids have been extensively studied and reported to possess widespread biological activities, including antioxidant and chelating properties. They have been proposed to exert beneficial effects in a multitude of diseased states generated due to oxidative stress. Therapeutic efficacy of oral administration of Silymarin and Quercetin after fluoride exposure (50 ppm in drinking water for 45 days) was investigated in rats. Animals exposed to fluoride showed a marked enhancement in reactive oxygen species (ROS), a significant decrease in reduced glutathione (GSH) in blood. In brain and kidney also, a significant elevation in ROS and Thiobarbituric Acid Substances (TBARS) level was noted accompanied by a significant decline in reduced/oxidized glutathione (GSH: GSSG) ratio. Furthermore, significant protection was observed in altered neurotransmitters level following the administration of Silymarin and Quercetin. Interestingly, both the flavonoids were able to reduce the level of fluoride from blood and kidney suggesting that the two flavonoids have the ability to bind fluoride ion too. It can be concluded from the results that, posttreatment with these flavonoids not only significantly protects against fluoride-induced oxidative stress but reduce its burden too from blood and tissues.

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References

  1. Whitford, G. M. The metabolism and toxicity of fluoride, 2nd rev. ed. Basel, Karger, pp. 156–170 (1996).

    Google Scholar 

  2. Eren, E., Ozturk, M., Mumcu, E. F. & Canatan, D. Fluorosis and its hematological effects. Toxicol Ind Hlth 21:255–258 (2005).

    Article  CAS  Google Scholar 

  3. Cicek, E., Aydin, G., Akdogan, M. & Okutan, H. Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats. Hum Exp Toxicol 24:79–87 (2005).

    Article  PubMed  CAS  Google Scholar 

  4. Guan, Z. et al. Changed cellular membrane lipid composition and lipid peroxidation of kidney in rats with chronic fluorosis. Arch Toxicol 74:602–608 (2000).

    Article  PubMed  CAS  Google Scholar 

  5. Chinoy, N. J. & Patel, T. N. Reversible toxicity of fluoride and aluminium in liver and gastrocinemius muscle of female mice. Fluoride 32:215–229 (1999).

    CAS  Google Scholar 

  6. Chinoy, N. J. & Patel, T. N. Effects of sodium fluoride and Aluminium Chloride on ovary and uterus of mice and their reversal by some antidotes. Fluoride 34:9–20 (2001).

    CAS  Google Scholar 

  7. Ghosh, D., Das Sarkar, S., Maiti, R., Jana, D. & Das, U. B. Testicular toxicity in sodium fluoride treated rats: association with oxidative stress. Reprod Toxicol 6:385–390 (2002).

    Article  Google Scholar 

  8. Guan, Z. Z. et al. Influence of chronic fluorosis on membrane lipids in rat brain. Neurotoxicol Teratol 20:537–542 (1999)

    Article  Google Scholar 

  9. Chouhan, S. & Flora, S. J. S. Effects of fluoride on the tissue oxidative stress and apoptosis in rats: Biochemical assays supported by IR spectroscopy data. Toxicology 254:61–67 (2008).

    Article  PubMed  CAS  Google Scholar 

  10. Chouhan, S., Lomash, V. & Flora, S. J. S. Fluorideinduced changes in haem biosynthesis pathway, neurological variables and tissue histopathology of rats. J App Toxicol 30:63–73 (2010).

    Article  CAS  Google Scholar 

  11. Pietta, P. G. Flavonoids as antioxidants. J Nat Prod 63:1035–1042 (2000)

    Article  PubMed  CAS  Google Scholar 

  12. Kren, V. & Walterová, D. Silybin and silymarin-new effects and applications. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 149:29–41 (2005).

    PubMed  CAS  Google Scholar 

  13. Ross, J. A. & Kasum, C. M. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22:19–34 (2002).

    Article  PubMed  CAS  Google Scholar 

  14. Boots, A. W. et al. The quercetin paradox. Toxicol Appl Pharmacol 222:89–96 (2007)

    Article  PubMed  CAS  Google Scholar 

  15. Rice-Evans, C. Flavonoid antioxidants. Curr Med Chem 8:797–807 (2001).

    PubMed  CAS  Google Scholar 

  16. Morales, A. I. et al. Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties. Food Chem Toxicol 44:2092–2100 (2006).

    Article  PubMed  CAS  Google Scholar 

  17. Mishra, D. & Flora, S. J. S. Quercetin administration during chelation therapy protects arsenic induced oxidative stress in mouse. Biol Trace Elem Res 122:137–147 (2008).

    Article  PubMed  CAS  Google Scholar 

  18. Abascal, K. & Yarnell, E. The many faces of silybum marianum (milk thistle). Alt Comp Ther 9:251–256 (2003)

    Article  Google Scholar 

  19. Pradhan, S. C. & Girish, C. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res 124:491–504 (2006).

    PubMed  CAS  Google Scholar 

  20. Osuchowski, M. F., Johnson, V. J., He, Q. & Sharma, R. P. Alterations in regional brain neurotransmitters by silymarin, a natural antioxidant flavonoid mixture, in BALB/c mice. Pharm Biol 42:384–389 (2004).

    Article  CAS  Google Scholar 

  21. Faria, A. et al. Flavonoid transport across RBE4 cells: A blood-brain barrier model. Cell Mol Biol Lett 15:234–241 (2010).

    Article  PubMed  CAS  Google Scholar 

  22. Czerny, A., Put, A., Myśliwiec, Z. & Juzyszyn, Z. The influence of quercetin on some biochemical parameters in rats exposed to environmental contamination with fluorine compounds b. Polish J Env Stud 9:157–161 (2000).

    CAS  Google Scholar 

  23. Juzyszyn, Z., Czerny, B., Myśliwiec, Z. & Put, A. Enhancement of kidney and liver respiratory activity by quercetin sulfonate in rats chronically exposed to ammonium fluoride. Fluoride 35:161–167 (2002).

    CAS  Google Scholar 

  24. Schmitt-schillig, S., Schaffer, S., Weber, C. C., Eckert, G. P. & Müller, W. E. Flavonoids and the aging brain. J Physiol Pharmacol 56:23–36 (2005).

    PubMed  Google Scholar 

  25. Nencini, C., Giorgi, G. & Micheli, L. Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine 14:129–135 (2007).

    Article  PubMed  CAS  Google Scholar 

  26. Pradeep, K., Mohan, C. V. R., Gobianand, K. & Karthikeyan, S. Silymarin modulates the oxidant-antioxidant imbalance during diethyl nitrosamine induced oxidative stress in rats. Eur J Pharmacol 560:110–116 (2007).

    Article  PubMed  CAS  Google Scholar 

  27. Muthukumaran, S., Sudheer, A. R., Menon, V. P. & Nalini, N. Protective effect of quercetin on nicotineinduced prooxidant and antioxidant imbalance and DNA damage in Wistar rats. Toxicology 14:207–215 (2008).

    Article  Google Scholar 

  28. Campos, R., Garrido, A., Guerra, R. & Valenzuela, A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 55:417–419 (1989).

    Article  PubMed  CAS  Google Scholar 

  29. Valenzuela, A., Lagos, C., Schmidt, K. & Videla, K. Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochem Pharmacol 3:2209–2212 (1985).

    Article  Google Scholar 

  30. Prior, R. L., Wu, X. & Gu, L. Flavonoid metabolism and challenges to understanding mechanisms of health effects. J Sci Food Agric 86:2487–2491 (2006).

    Article  CAS  Google Scholar 

  31. Bors, W., Michel, C. & Saran, M. Flavonoid antioxidants: rate constants for reactions with oxygen radicals. Methods Enzymol 234:420–429 (1994).

    Article  PubMed  CAS  Google Scholar 

  32. Yanni, Y. et al. Neurotransmitter and receptor changes in the brains of fetuses from areas of endemic fluorosis. Translated research report. Fluoride 41:134–138 (2008).

    Google Scholar 

  33. Dajas, F. et al. Neuroprotection by flavonoids. Braz. J Med. Biol Res 3:1613–1620 (2003).

    Article  Google Scholar 

  34. Bors, W., Heller, W., Michel, C. & Saran, M. Flavonoids as antioxidants: determination of radical scavenging efficiencies. Meth. Enzymol 186:343–355 (1990).

    Article  PubMed  CAS  Google Scholar 

  35. Ellman, G. L. Tissue sulphydryl groups. Arch Biochem 82:70–77 (1959).

    Article  PubMed  CAS  Google Scholar 

  36. Jollow, D. J., Mitchell, J. R., Zamppaglione, Z. & Gillette, J. R. Bromobenzene induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolites. Pharmacol 11:151–169 (1974).

    Article  CAS  Google Scholar 

  37. Socci, D. J., Bjugstad, K. B., Jones, H. C., Pattisapu, J. V. & Arendash, G.W. Evidence that oxidative stress is associated with the pathophysiology of inherited hydrocephalus in the H-Tx rat model. Exp Neurol 155:109–117 (1999).

    Article  PubMed  CAS  Google Scholar 

  38. Hissin, P. J. & Hilf, R. A fluorometric method for the determination of oxidized and reduced glutathione in tissue. Anal Biochem 74:214–226 (1973).

    Article  Google Scholar 

  39. Ohkawa, H., Onishi, N. & Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358 (1979).

    Article  PubMed  CAS  Google Scholar 

  40. Jacobwitz, D. W. & Richardson, J. S. Method for rapid determination of norepinephrine, dopamine and serotonin in the same brain region. Pharmacol Biochem Behav 8:515–519 (1978).

    Article  Google Scholar 

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Authors and Affiliations

  1. Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India

    Swapnila Chouhan, Abhishek Yadav, Pramod Kushwah, Ramesh K. Kaul & Swaran J. S. Flora

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  1. Swapnila Chouhan
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  2. Abhishek Yadav
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  3. Pramod Kushwah
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  4. Ramesh K. Kaul
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  5. Swaran J. S. Flora
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Correspondence to Swaran J. S. Flora.

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Chouhan, S., Yadav, A., Kushwah, P. et al. Silymarin and quercetin abrogates fluoride induced oxidative stress and toxic effects in rats. Mol. Cell. Toxicol. 7, 25–32 (2011). https://doi.org/10.1007/s13273-011-0004-2

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  • DOI: https://doi.org/10.1007/s13273-011-0004-2

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