Protective Effect of d-Limonene Experimentally Induced Cardiotoxicity in Wistar Albino Rats

Authors

  • Palanisamy Krishnan  Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India
  • Sathesh Kanna Velli  Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India
  • Sharmila Salam  Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India
  • Manikandan Murugan  Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India
  • Jagan Sundaram  Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India
  • Devaki Thiruvengadam  Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India

Keywords:

Cyclophosphamide, D-Limonene, Cardiotoxicity,

Abstract

Cyclophosphamide (CP) is one of the most widely used alkylating antineoplastic agents that damages normal cells while killing cancerous cells. The consumption of CP in treating cancer patients is limited due to its severe toxicity induced mainly by cardiac toxicity. Toxicity profiles of diverse anti-neoplastic drugs are extensively documented in past decades and the protective role of natural compounds against such toxic drugs plays a vital role in the evolution of chemoprevention. Hence the present study was designed to investigate the protective role of d-Limonene against CP induced cardio toxicity in male Wistar rats. The dose fixation studies the experimental designs were segregated into four groups for the cardio protective analysis in CP induced cardiotoxicity for 10 days. After the experimental period the body weight, relative heart weight, the level of lipid peroxidation, the activities of antioxidant enzymes were assessed. The administration of CP to rats results in increased relative heart weight and serum marker enzymes ,and significant increase in cardiac lipid level, and significant decrease in the final body weight, cardiac mitochondrial dysfunction, tissue damage and the pathological changes assessed by histology study. Supplementation of d-Limonene significantly normalized the level of serum marker enzymes, and cardiac lipid level, cardiac mitochondrial function and cardiac function.

References

  1. Ratain MJ, Plunkett W. Principles for chemotherapy, pharmacology. In: Holland JF, Frei Jr EI, Bast RC, Kufe DW, Morton DC, Weiehselbaum RR. editors. Cancer med Baltimore, MD’ Williams and Wilkins; 1997. p. 875-90.
  2. Colombo P, Gunnarsson K, Latropoulos M, Brugera M. Toxicological testing of cytotoxic drugs (Review). Int J Oncol 2001;19:1021-8.
  3. Sulkowska M, Skrzydlewska E, Sobamee-Lotowska M, Famulski W, Terlikowski S, Reszee J. Effect of cyclophosphamide induced generation forms on ultrastructure of the liver and lung. Bull Vet Inst Pulawy 2002;46:239-46.
  4. Dollery C, Cyclophosphamide. In: Dollery C. Ed. Therapeutic Drugs. Churchill Livingstone, Edinburg; 1999. p. 349-53.
  5. Goldberg MA, Antin JH, Guinan EC, Rappeport JM. Cyclophosphamide cardiotoxicity: an analysis of doing as a risk factor. Blood 1986;68:1114-8.
  6. Bukowski R. The need for cytoprotection. Eur J Cancer 1999;32A Suppl 4:S2-4.
  7. Fraiser LH, Kanekel S, Kehrer JP. Cyclophosphamide toxicity. Characterizing and avoiding the problem. Drugs 1991;42:781-95.
  8. Sladek N. Metabolism of cyclophosphamide by rat hepatic microsomes. Cancer Res 1971;1:901-8.
  9. Sladek NE. Metabolism of oxazaphosphorines. Pharmacol Ther 1988;37:301-55.
  10. Shanholtz C. Acute life-threatening toxicity of cancer treatment. Crit Care Clin 2001;17:483-502.
  11. Schimmel KJ, Richel DJ, van den Brink RB, Guchelaar HJ. Cardiotoxicity of cytotoxic drugs. Cancer Treat Rev 2004;30:181-91.
  12. Loudet AM, Dousset N, Carton M, Douste-Blazy L. Effects of an antimitotic agent (cyclophosphamide) on plasma lipoproteins. Biochem Pharmacol 1984;33:2961-5.
  13. Lespine A, Chap H, Perret B. Impaired secretion of heart lipoprotein lipase in cyclophosphamide-treated rabbit. Biochem Biophys Acta 1997;1345:77-85.
  14. Al-Nasser IA. In vivo prevention of cyclophosphamide induced Ca dependent damage of rat heart and liver mitochondria by cyclosporin A. Comp Biochem Physiol Part A: Mol Integr Physiol 1998;121:209-14. 2+
  15. Mythili Y, Sudharsan PT, Varalakshmi P. DL-a-lipoic acid ameliorates cyclophosphamide induced cardiac mitochondrial injury. Toxicology 2005;215:108-14.
  16. Santos GW, Sensenbrenner LL, Burke PJ. The use of cyclophosphamide for clinical marrow transplantation. Transplant Proc 1972;4:559-64.
  17. Gottdiener JS, Applebaum ER, Ferrans VJ, Deisseroth A, Ziegler J. Cardiotoxicity associated with high-dose Cyclophosphamide therapy. Arch Intern Med 1981;141:758-63.
  18. Goldberg MA, Antin JH, Guiman EC, Rappeport JM. Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. Blood 1986;68:1114-8.
  19. Birchall IW, Lalani Z, Venner P, Hugh J. Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy. Br J Radiol 2000;73:1112-4.
  20. Kamezaki K, Fukuda T, Makino S, Harada M. Cyclophosphamide induced cardiomyopathy in a patient with seminoma and a history of mediastinal irradiation. Intern Med 2005;44:120-3.
  21. Rajendran R, Ganesan N, Balu SK, Alagar S, Thandavamoorthy P, Thiruvengadam D. Green synthesize, characterization, antimicrobial and cytotoxic effects of silver nanoparticles using O. heracleoticumL. leaf extract. Int J Pharm Pharm Sci 2015;7:288-93.
  22. Balan R, Rajendran R, Thandavamoorthy P, Thiruvengadam D. Carvacrol attenuates N-nitrosodiethylamine induced liver injury in experimental Wistar rats. Food Sci Hum Wellness 2015. doi.org/10.1016/j.fshw.2015.04.002. [Article in Press]
  23. Kalemda D, Kunicka A. Antibacterial and antifungal properties of essential oils. Curr Med Chem 2003;10:813-29.
  24. Edris AE. Pharmaceutical and therapeutic potentials of essential oils and their individual volatile constituents: a review. Phytother Res 2007;21:308-23.
  25. Thandavamoothy P, Balan R, Subramaniyan J, Arumugam M, John B, Krishnan G, et al. Alleviative role of rutin against 4Nitroquinoline-1-Oxide (4-NQO) provoked oral squamous cell carcinoma in experimental animal model. J Pharm Res 2014;8:899-906.
  26. Croteau R, Biosynthesis and catabolism of monoterpenes. Chem Rev 1987; 87:929
  27. Wattenberg LW, Inhibition of carcinogenesis by minor a nutrient constituents of the diet. Proc Nutr Soc 1990; 49:173-183
  28. Marshall JR, Improving American’s diet-setting public policy with limited knowledge. Am J Public Health 1995; 85:1609-11
  29. Pandima Devi K, Sreepriya M, Balakrishna K, Devaki T, Protective effect of Premna tomentosa (L. Verbenaceae) extracts on membrane-bound phosphatases and inorganic cations transport in acetaminophen-induced hepatotoxicity rats. J Ethnopharmacol 2004; 93:371-5
  30. Reicks MM, Crankshaw D, Effects of d-Limonene on hepatic microsomal monooxygenase activity and paracetamolinduced glutathione depletion in mouse. Xenobiotica 1993; 23:809-19.
  31. Van Lieshout EM, Posner GH, Woodard BT, Peters WH, Effects of the sulforaphane analog compound 30, indole-3-carbinol, d-Limonene or relafen on glutathione S- transferases and glutathione peroxidase of the rat digestive tract. Biochim Biophys Acta 1998; 1379:325-336.
  32. Crowell PL, Elson CE, Bailey HH, et al. Human metabolism of the experimental cancer therapeutic agent d-Limonene. Cancer Chemother Pharmacol 1994; 35:31-37
  33. Bodake HB, Panicker KN, Kailaje VV, Rao KV, Chemopreventive effect of orange oil on the development of hepatic preneoplastic lesions induced by N-nitrosodiethylamine in rats: an ultrastructural study. Indian J Exp Biol 2002; 40:245-51.
  34. Del Toro-Arreola S, Flores-Torales E, Torres-Lozano C, ToroArreola AD, Tostado- Pelayo K, Ramirez-Duenas MG, DaneriNavarro A, Effect of d-Limonene on immune response in BALB/c mice with lymphoma. Int Immunopharmacol 2005; 5:829-38
  35. Okinaka, S., Sugita, H., Mamoi, T (1964). Cysteine-stimulated serum creatine kinase in health and disease. J Lab Clin Med; 64:299-305.
  36. King, J. (1965). The dehydrogenases or oxidoreductases-lactate dehydrogense. In: Van D. editor. Practical clinical enzymology; London: Nostrand; p. 83-93.
  37. Mohun, A.F., Cook, L.J (1957). Simple method for measuring serum level of glutamateoxaloacetate and glutamate-pyruvate transaminases in laboratories. J Clin Chem; 10:394-9.
  38. King, J. (1965). Van. editor. Practical clinical enzymology. London: Nostrand; p. 363.
  39. Misra, H.P., Fridovich, J (1972). The role of superoxide anion in the auto-oxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem; 247:3170-5.
  40. Bergmeyer, H.V., Gowehn, K., Grassel, M (1974). Methods of enzymatic analysis. New York: Academic; p. 438.
  41. Rotruck, J.T., Pope, A.L., Ganther, H.E (1973). Selenium: biochemical role as a component of glutathione peroxidase, purification and assay. Science; 179:588-90.
  42. Habig, W.H., Pabs, J (1974). Glutathione-S-transferase. J Biol Chem; 249:7130-9.
  43. Beutler, E., Matsumoto, F (1975). Ethinic variation in red cell glutathione peroxidase activity. Blood; 46:103-10.
  44. Omaye, S.T., Turbull, T.P., Sauberchich, H.C (1979). Selected methods for determination of ascorbic acid in cells, tissues and fluids. Methods Enzymol; 6:3-11.
  45. Desai, I.D (1984). Vitamin E analysis methods for animal tissues. Methods Enzymol; 105:138 47.
  46. Bayfield, R.F., Cole, E.R (1980). Colorimetric estimation of vitamin A with trichloroacetic acid. Methods Enzymol; 67:189-203.
  47. Staal, G.E.J., Visser, J., Veger, C (1969). Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta; 185:39-48.
  48. Wilson, D.F., Spiger, M.J (1973). A dual precipitation method for quantitative plasma lipoprotein measurement without ultracentrifugation. J Lab Clin Med; 82:473-82.
  49. Asiri, Yousif A. Probucol attenuates cyclophosphamide-induced oxidative apoptosis, P53 and bax signal expression in rat cardiac tissues. Oxid Med Cell Longevity 2010;308-16.
  50. Nagi, Mahmoud N. Thymoquinone supplementation attenuates Cyclophosphamide-induced cardiotoxicity in rats. J Biochem Mol Toxicol 2010;25:135-42.
  51. Singh, Ravinder J. Glutathione: a marker and antioxidant for aging. J Lab Clin Med 2002;140:380-1.
  52. Mantawy, Eman M. Chrysin alleviates acute doxorubicin cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis'. Eur J Pharmacol 2014;728:107-18.

International Journal of Scientific Research in Science and Technology

Downloads

Published

2017-08-31

Issue

Volume 3, Issue 6, July-August-2017

Section

Research Articles

License

Copyright (c) IJSRST

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

[1]
Palanisamy Krishnan, Sathesh Kanna Velli, Sharmila Salam, Manikandan Murugan, Jagan Sundaram, Devaki Thiruvengadam, " Protective Effect of d-Limonene Experimentally Induced Cardiotoxicity in Wistar Albino Rats, International Journal of Scientific Research in Science and Technology(IJSRST), Online ISSN : 2395-602X, Print ISSN : 2395-6011, Volume 3, Issue 6, pp.328-336, July-August-2017.