Skip to main content
SpringerLink
Log in

Protective Role of Tetrahydrocurcumin: an Active Polyphenolic Curcuminoid on Cadmium-InducedOxidative Damage in Rats

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

In the present work, protective effect of tetrahydrocurcumin (THC) against oxidative damages in cadmium (Cd)-induced toxicity in rats was evaluated. Cd is an important environmental and industrial toxicant that affects almost all the organs, especially liver. Liver is the major organ responsible for the metabolism and the primary target for many toxic chemicals and drugs. Effect of THC, the curcumin-derived polyphenolic compound on Cd-induced oxidative stress and hepatic damage was evaluated using male albino Wistar rats. In Cd-administered rats (5 mg/kg body weight (b.w.), orally for 4 weeks), activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) were significantly increased in serum with the elevated level of bilirubin. Red blood cells (RBC), haemoglobin contents and haematocrit values were also significantly decreased in Cd-treated rats. In addition, the levels of lipid peroxidation markers like thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LHP), protein carbonyl contents (PCC) and conjugated dienes (CD) were significantly increased followed by the significant decrease in the levels of reduced glutathione (GSH), total sulphydryl groups (TSH), ascorbic acid (vitamin C) and vitamin E in liver of Cd-administered rats. Oral administration of THC (20, 40 and 80 mg/kg b.w.) followed by Cd for 4 weeks showed a significant restoration of the above changes to near normal. Histopathological changes observed in Cd intoxicated hepatic tissues were minimized on treatment with THC. This study suggests that THC at the dose of 80 mg/kg b.w. effectively subdues the Cd-induced toxicity and controls the free radical-induced liver damage in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Xiao, P., Jia, X. D., Zhong, W. J., Jin, X. P., & Nordberg, G. U. N. N. A. R. (2002). Restorative effects of zinc and selenium on cadmium-induced kidney oxidative damage in rats. Biomedical and Environmental Science, 15(1), 67–74.

    Google Scholar 

  2. Bernard, A. (2008). Cadmium and its adverse effects on human health. Indian Journal of Medical Research, 128, 557–564.

    CAS  Google Scholar 

  3. Thijssen, S., Cuypers, A., Maringwa, J., Smeets, K., Horemans, N., Lambrichts, I., & Van Kerkhove, E. (2007). Low cadmium exposure triggers a biphasic oxidative stress response in mice kidneys. Toxicology, 236(1), 29–41.

    Article  CAS  Google Scholar 

  4. Kara, H., Cevik, A., Konar, V., Dayangac, A., & Yilmaz, M. (2007). Protective effects of antioxidants against cadmium-induced oxidative damage in rat testes. Biological Trace Element Research, 120(1–3), 205–211.

    Article  CAS  Google Scholar 

  5. Konar, V., Kara, H., Yilmaz, M., Dayangac, A., & Karatas, F. (2007). Effects of selenium and vitamin E, in addition to melatonin, against oxidative stress caused by cadmium in rats. Biological Trace Element Research, 118(2), 131–137.

    Article  CAS  Google Scholar 

  6. Everett, C. J., & Frithsen, I. L. (2008). Association of urinary cadmium and myocardial infarction. Environmental Research, 106(2), 284–286.

    Article  CAS  Google Scholar 

  7. Yiin, S. J., Chern, C. L., Sheu, J. Y., Tseng, W. C., & Lin, T. H. (1999). Cadmium-induced renal lipid peroxidation in rats and protection by selenium. Journal of Toxicology and Environmental Health, A, 57(6), 403–413.

    Article  CAS  Google Scholar 

  8. Pandey, S., Parvez, S., Ansari, R. A., Ali, M., Kaur, M., Hayat, F., et al. (2008). Effects of exposure to multiple trace metals on biochemical, histological and ultrastructural features of gills of a freshwater fish, Channa punctata Bloch. Chemico-Biological Interactions, 174(3), 183–192.

    Article  CAS  Google Scholar 

  9. Nawrot, T., Plusquin, M., Hogervorst, J., Roels, H. A., Celis, H., Thijs, L., et al. (2006). Environmental exposure to cadmium and risk of cancer: a prospective population-based study. Lancet Oncology, 7(2), 119–126.

    Article  CAS  Google Scholar 

  10. Eybl, V., Kotyzová, D., & Bludovská, M. (2004). The effect of curcumin on cadmium-induced oxidative damage and trace elements level in the liver of rats and mice. Toxicology Letters, 151(1), 79–85.

    Article  CAS  Google Scholar 

  11. Prakash, A. S., Tran, H. P., Peng, C., Koyalamudi, S. R., & Dameron, C. T. (2000). Kinetics of DNA alkylation, depurination and hydrolysis of anti diol epoxide of benzo (a) pyrene and the effect of cadmium on DNA alkylation. Chemico-Biological Interactions, 125(2), 133–150.

    Article  CAS  Google Scholar 

  12. Youdim, K. A., & Joseph, J. A. (2001). A possible emerging role of phytochemicals in improving age-related neurological dysfunctions: a multiplicity of effects. Free Radical Biology and Medicine, 30(6), 583–594.

    Article  CAS  Google Scholar 

  13. Shagirtha, K., & Pari, L. (2011). Hesperetin, a citrus flavonone, attenuates cadmium-induced nephrotoxicity in rat. Biomedicine and Preventive Nutrition, 1(2), 139–145.

    Article  Google Scholar 

  14. Anand, P., Kunnumakkara, A. B., Newman, R. A., & Aggarwal, B. B. (2007). Bioavailability of curcumin: problems and promises. Molecular Pharmaceutics, 4(6), 807–818.

    Article  CAS  Google Scholar 

  15. Majeed, M., Badmaev, V., Uma, S., & Rajenderan, J. R. (1995). Curcuminoids: antioxidant Phytonutrients (pp. 1–24). New Jersey: Nutreiscience publishers.

    Google Scholar 

  16. Sugiyama, Y., Kawakishi, S., & Osawa, T. (1996). Involvement of the β-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin. Biochemical Pharmacology, 52(4), 519–525.

    Article  CAS  Google Scholar 

  17. Lai, C. S., Wu, J. C., Yu, S. F., Badmaev, V., Nagabhushanam, K., Ho, C. T., & Pan, M. H. (2011). Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis. Molecular Nutrition & Food Research, 55(12), 1819–1828.

    Article  CAS  Google Scholar 

  18. Lin, J. K., & Lin-Shiau, S. Y. (2001). Mechanisms of cancer chemoprevention by curcumin. Pro. Nat. Sci. Coun. Rep China Part B, Life Sciences, 25(2), 59–66.

    CAS  Google Scholar 

  19. Naito, M., Wu, X., Nomura, H., Kodama, M., Kato, Y., Kato, Y., & Osawa, T. (2002). The protective effects of tetrahydrocurcumin on oxidative stress in cholesterol-fed rabbits. Journal of Atherosclerosis and Thrombosis, 9(5), 243–250.

    Article  CAS  Google Scholar 

  20. Pari, L., & Murugan, P. (2004). Protective role of tetrahydrocurcumin against erythromycin estolate-induced hepatotoxicity. Pharmaceutical Research, 49(5), 481–486.

    Article  CAS  Google Scholar 

  21. Renugadevi, J., & Prabu, S. M. (2009). Naringenin protects against cadmium-induced oxidative renal dysfunction in rats. Toxicology, 256(1), 128–134.

    Article  CAS  Google Scholar 

  22. Amudha, K., & Pari, L. (2011). Beneficial role of naringin, a flavanoid on nickel induced nephrotoxicity in rats. Chemico-Biological Interactions, 193(1), 57–64.

    Article  CAS  Google Scholar 

  23. Shirley, R. L., Benne, E. J., & Miller, E. J. (1949). Cadmium in biological materials and foods. Analytical Chemistry, 21(2), 300–303.

    Article  CAS  Google Scholar 

  24. Malloy, H. T., & Evelyn, K. A. (1937). The determination of bilirubin with the photoelectric colorimeter. The Journal of Biological Chemistry, 119(2), 481–490.

    CAS  Google Scholar 

  25. Niehaus, W. G., & Samuelsson, B. (1968). Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. European Journal of Biochemistry, 6(1), 126–130.

    Article  CAS  Google Scholar 

  26. Jiang, Z. Y., Hunt, J. V., & Wolff, S. P. (1992). Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Analytical Chemistry, 202(2), 384–389.

    CAS  Google Scholar 

  27. Levine, R. L., Garland, D., Oliver, C. N., Amici, A., Climent, I., Lenz, A.-G., Ahn, B.-W., Shaltiel, S., & Stadtman, E. R. (1990). Determination of carbonyl content in oxidatively modified proteins. Methods Enzymology, 186, 465–478.

    Google Scholar 

  28. Rao, K. S., & Recknagel, R. O. (1968). Early onset of lipoperoxidation in rat liver after carbon tetrachloride administration. Experimental and Molecular Pathology, 9(2), 271–278.

    Article  CAS  Google Scholar 

  29. Kakkar, P., Das, B., & Viswanathan, P. N. (1984). A modified spectrophotometric assay of superoxide dismutase. Indian Journal of Biochemistry and Biophysics, 21(2), 130–132.

    CAS  Google Scholar 

  30. Sinha, A. K. (1972). Colorimetric assay of catalase. Analytical Chemistry, 47(2), 389–394.

    CAS  Google Scholar 

  31. Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., & Hoekstra, W. (1973). Selenium: biochemical role as a component of glutathione peroxidase. Science, 179(4073), 588–590.

    Article  CAS  Google Scholar 

  32. Habig, W. H., Pabst, M. J., & Jakoby, W. B. (1974). Glutathione S-transferases the first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 249(22), 7130–7139.

    CAS  Google Scholar 

  33. Horn, H. D., & Burns, F. H. (1978). Assay of glutathione reductase activity. In H. V. Bergemeyer (Ed.), Methods of enzymatic analysis (pp. 142–146). New York: Academic Press.

    Google Scholar 

  34. Beutler, E. (1983). Active transport of glutathione disulfide from erythrocytes. In A. Larson, S. Orrenius, A. Holmgren, & B. Mannerwik (Eds.), Functions of glutathione-biochemical, physiological (pp. 65–74). New York: Toxicological and Clinical Aspects. Raven Press.

    Google Scholar 

  35. Omaye, S. T., Turnbull, J. D., & Sauberlich, H. E. (1979). Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods in enzymology, 62, 3–11.

    Article  CAS  Google Scholar 

  36. Desai, I. D. (1984). Vitamin E analysis methods for animal tissues [Alpha tocopherol]. Methods in Enzymology (USA).

  37. Zahler, W. L., & Cleland, W. W. (1968). A specific and sensitive assay for disulfides. Journal of Biological Chemistry, 243(4), 716–719.

    CAS  Google Scholar 

  38. Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1–2), 248–254.

    Article  CAS  Google Scholar 

  39. Duncan, D. B. (1957). Multiple range tests for correlated and heteroscedastic means. Biometrics, 13(2), 164–176.

    Article  Google Scholar 

  40. Pari, L., & Murugavel, P. (2005). Role of diallyl tetrasulfide in ameliorating the cadmium induced biochemical changes in rats. Environmental Toxicology and Pharmacology, 20(3), 493–500.

    Article  CAS  Google Scholar 

  41. Girault, L., Boudou, A., & Dufourc, E. J. (1998). 113 Cd-, 31 P-NMR and fluorescence polarization studies of cadmium (II) interactions with phospholipids in model membranes. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1414(1), 140–154.

    Article  CAS  Google Scholar 

  42. Sundberg, A., Appelkvist, E. L., Dallner, G., & Nilsson, R. (1994). Glutathione transferases in the urine: sensitive methods for detection of kidney damage induced by nephrotoxic agents in humans. Environmental Health Perspectives, 102(Suppl 3), 293.

    Article  CAS  Google Scholar 

  43. Drozdz, R., Parmentier, C., Hachad, H., Leroy, P., Gérard Siest, G., & Wellman, M. (1998). γ-glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radical Biology and Medicine, 25(7), 786–792.

    Article  CAS  Google Scholar 

  44. Whitfield, J. B. (2001). Gamma glutamyl transferase. Critical Reviews in Clinical Laboratory Sciences, 38(4), 263–355.

    Article  CAS  Google Scholar 

  45. Lee, D. H., Blomhoff, R., & Jacobs, D. R. (2004). Review is serum gamma glutamyltransferase a marker of oxidative stress? Free Radical Research, 38(6), 535–539.

    Article  CAS  Google Scholar 

  46. Sarkar, S., Yadav, P., & Bhatnagar, D. (1998). Lipid peroxidative damage on cadmium exposure and alterations in antioxidantsystem in rat erythrocytes: a study with relation to time. Biometals, 11(2), 153–157.

    Article  CAS  Google Scholar 

  47. Luchese, C., Zeni, G., Rocha, J. B., Nogueira, C. W., & Santos, F. W. (2007). Cadmium inhibits δ-aminolevulinate dehydratase from rat lung in vitro: interaction with chelating and antioxidant agents. Chemico-Biological Interactions, 165(2), 127–137.

    Article  CAS  Google Scholar 

  48. Hamada, T., Tanimoto, A., Arima, N., Ide, Y., Sasaguri, T., Shimajiri, S., & Sasaguri, Y. (1998). Altered membrane skeleton of red blood cells participates in cadmium-induced anemia. IUBMB Life, 45(4), 841–847.

    Article  CAS  Google Scholar 

  49. Kłapcińska, B., Poprzecki, S., Dolezych, B., & Kimsa, E. (2000). Cadmium-induced changes in hematology and 2,3-DPG levels in rats. Bulletin of Environmental Contamination and Toxicology, 64(1), 93–99.

    Article  Google Scholar 

  50. Klaassen, C. D., Liu, J., & Choudhuri, S. (1999). Metallothionein: an intracellular protein to protect against cadmium toxicity. Annual Review of Pharmacology and Toxicology, 39(1), 267–294.

    Article  CAS  Google Scholar 

  51. Nakamoto, K. (1977). Infrared and Raman spectra of inorganic and coordination compounds. Wiley.

  52. Hussain, T., Shukla, G. S., & Chandra, S. V. (1987). Effects of cadmium on superoxide dismutase and lipid peroxidation in liver and kidney of growing rats: in vivo and in vitro studies. Pharmacology & Toxicology, 60(5), 355–358.

    Article  CAS  Google Scholar 

  53. Manca, D., Ricard, A. C., Trottier, B., & Chevalier, G. (1991). Studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride. Toxicology, 67(3), 303–323.

    Article  CAS  Google Scholar 

  54. Stohs, S. J., & Bagchi, D. (1995). Oxidative mechanisms in the toxicity of metal ions. Free Radical Research, 18(2), 321–336.

    Article  CAS  Google Scholar 

  55. Rikans, L. E., & Yamano, T. (2000). Mechanisms of cadmium-mediated acute hepatotoxicity. Journal of Biochemical and Molecular Toxicology, 14(2), 110–117.

    Article  CAS  Google Scholar 

  56. Wang, Y., Fang, J., Leonard, S. S., & Rao, K. M. K. (2004). Cadmium inhibits the electron transfer chain and induces reactive oxygen species. Journal of Biochemical and Molecular Toxicology, 36(11), 1434–1443.

    CAS  Google Scholar 

  57. Ognjanović, B. I., Pavlović, S. Z., Maletić, S. D., Zikić, R. V., Stajn, A. S., Radojicić, R. M., et al. (2003). Protective influence of vitamin E on antioxidant defense system in the blood of rats treated with cadmium. Physiological Research, 52(5), 563–570.

    Google Scholar 

  58. Prabu, M. S., Selvarajan, N., Hemalatha, S., & Rameshkumar, T. (2008). Hepatoprotective effect of Andrographis paniculata against cadmium induced toxicity in male Wistar rats. Toxicology Int., 15(1), 21.

    Google Scholar 

  59. Borsook, H., & Keighley, G. (1933). Oxidation-reduction potential of ascorbic acid (vitamin C). Proceedings of the National Academy of Sciences, 19(9), 875–878.

    Article  CAS  Google Scholar 

  60. Chatterjee, G. C., Banerjee, S. K., & Pal, D. R. (1972). Cadmium administration and L-ascorbic acid metabolism in rats: effect of L-ascorbic acid supplementation. Internationale Zeitschrift fur vitamin-und Ernahrungsforschung International Journal for Vitamin and Nutrition Research, 43(3), 370–377.

    Google Scholar 

  61. Hudecova, A., & Ginter, E. (1992). The influence of ascorbic acid on lipid peroxidation in Guinea pigs intoxicated with cadmium. Food and Chemical Toxicology, 30(12), 1011–1013.

    Article  CAS  Google Scholar 

  62. Pavlovic, S. Z., Ognjanovic, B. I., Stajn, A. S., Zikic, R. V., Saicic, Z. S., & Petrovic, V. M. (2001). The effect of coenzyme Q 10 on blood ascorbic acid, vitamin E, and lipid peroxide in chronic cadmium intoxication. Journal of Environmental Pathology, Toxicology and Oncology, 20(2).

  63. Rana, S. V. S., & Verma, S. (1996). Protective effects of GSH, vitamin E, and selenium on lipid peroxidation in cadmium-fed rats. Biological Trace Element Research, 51(2), 161–168.

    Article  CAS  Google Scholar 

  64. Griffith, O. W. (1999). Biologic and pharmacologic regulation of mammalian glutathione synthesis. Free Radical Biology and Medicine, 27(9), 922–935.

    Article  CAS  Google Scholar 

  65. Navarro, F., Arroyo, A., Martín, S. F., Bello, R. I., De Cabo, R., Burgess, J. R., et al. (1999). Protective role of ubiquinone in vitamin E and selenium-deficient plasma membranes. BioFactors, 9(2–4), 163–170.

    Article  CAS  Google Scholar 

  66. El-Demerdash, F. M., Yousef, M. I., Kedwany, F. S., & Baghdadi, H. H. (2004). Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and β-carotene. Food and Chemmical Toxicology, (10), 1563–1571.

  67. Bauer, R., Demeter, I., Hasemann, V., & Johansen, J. T. (1980). Structural properties of the zinc site in Cu, Zn-superoxide dismutase; perturbed angular correlation of gamma ray spectroscopy on the Cu, 111 Cd-superoxide dismutase derivative. Biochemical and Biophysical Research Communications, 94(4), 1296–1302.

    Article  CAS  Google Scholar 

  68. Li, W. D., Kagan, H. M., & Chou, I. N. (1994). Alterations in cytoskeletal organization and homeostasis of cellular thiols in cadmium-resistant cellsToxicology and. Applied Pharmacology, 126(1), 114–123.

    Article  CAS  Google Scholar 

  69. Freeman, B. A., & Crapo, J. D. (1982). Biology of disease: free radicals and tissue injury. Laboratory investigation; a journal of technical methods and pathology, 47(5), 412–426.

    CAS  Google Scholar 

  70. Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82(1), 70–77.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are deeply grateful to Ministry of Environment and Forests for the constant financial (19-35/2009-RE/09-11-2010) and moral support towards the successful completion of this study.

Author information

Authors and Affiliations

  1. Department of Biochemistry, St. Joseph’s College of Arts & Science (Autonomous), Cuddalore, 607001, Tamil Nadu, India

    Ramalingam Ramakrishnan

  2. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tami Nadu, 608002, India

    Perumal Elangovan & Leelavinothan Pari

Authors
  1. Ramalingam Ramakrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Perumal Elangovan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leelavinothan Pari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ramalingam Ramakrishnan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramakrishnan, R., Elangovan, P. & Pari, L. Protective Role of Tetrahydrocurcumin: an Active Polyphenolic Curcuminoid on Cadmium-InducedOxidative Damage in Rats. Appl Biochem Biotechnol 183, 51–69 (2017). https://doi.org/10.1007/s12010-017-2430-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-017-2430-7

Keywords

Search

Navigation