Cardiovascular Toxicology

, Volume 18, Issue 4, pp 337–345 | Cite as

Protective Effect of Ellagic Acid Against Sodium Arsenite-Induced Cardio- and Hematotoxicity in Rats

  • Mehdi Goudarzi
  • Iman Fatemi
  • Amir Siahpoosh
  • Seyed Hashem Sezavar
  • Esrafil Mansouri
  • Saeed MehrzadiEmail author


Ellagic acid (EA) is a phenolic constituent in certain fruits and nuts with wide range of biological activities, including potent antioxidant, antidiabetic, anti-inflammatory, anticancer and antimutagen properties. The aim of this study was to evaluate the effect of EA on sodium arsenic (SA)-induced cardio- and hematotoxicity in rats. Animals were divided into five groups. The first group was used as control. Group 2 was orally treated with sodium arsenite (SA, 10 mg/kg) for 21 days. Group 3 was orally treated with EA (30 mg/kg) for 14 days. Groups 4 and 5 were orally treated with SA for 7 days prior to EA (10 and 30 mg/kg, respectively) treatment and continued up to 21 days simultaneous with SA administration. Various biochemical, histological and molecular biomarkers were assessed in blood and heart. The results indicate that SA-intoxicated rats display significantly higher levels of plasma cardiac markers (AST, CK-MB, LDH and cTnI) than normal control animals. Moreover, an increase in MDA and NO with depletion of GSH and activities of CAT, SOD and GPx occurred in the heart of rats treated with SA. Furthermore, SA-treated rats showed significantly lower WBC, RBC, HGB, HCT and PLT and significantly higher MCV and MCH. Administration of EA (30 mg/kg) resulted in a significant reversal of hematological and cardiac markers in arsenic-intoxicated rats. These biochemical disturbances were supported by histopathological observations of the heart. In conclusion, the results of this study suggest that EA treatment exerts a significant protective effect on SA-induced cardio- and hematotoxicity.


Sodium arsenite Ellagic acid Hematological parameters Cardioprotection Rat 



This study was funded by Deputy of Research of Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (Grant Number 95s35).

Compliance with Ethical Standards

Conflict of interest

Authors declare no conflict of interest related to this study.


  1. 1.
    Jiang, J. Q., Ashekuzzaman, S. M., Jiang, A., Sharifuzzaman, S. M., & Chowdhury, S. R. (2012). Arsenic contaminated groundwater and its treatment options in Bangladesh. International Journal of Environmental Research and Public Health, 10, 18–46.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Anetor, J. I., Wanibuchi, H., & Fukushima, S. (2007). Arsenic exposure and its health effects and risk of cancer in developing countries: Micronutrients as host defence. Asian Pacific Journal of Cancer Prevention: APJCP, 8, 13–23.PubMedGoogle Scholar
  3. 3.
    Hughes, M. F. (2002). Arsenic toxicity and potential mechanisms of action. Toxicology Letters, 133, 1–16.CrossRefPubMedGoogle Scholar
  4. 4.
    Jalaludeen, A. M., Ha, W. T., Lee, R., Kim, J. H., Do, J. T., Park, C., et al. (2016). Biochanin a ameliorates arsenic-induced hepato- and hematotoxicity in rats. Molecules, 21, 69.CrossRefPubMedGoogle Scholar
  5. 5.
    Shi, H., Shi, X., & Liu, K. J. (2004). Oxidative mechanism of arsenic toxicity and carcinogenesis. Molecular and Cellular Biochemistry, 255, 67–78.CrossRefPubMedGoogle Scholar
  6. 6.
    Pachauri, V., & Flora, S. (2013). Effect of nicotine pretreatment on arsenic-induced oxidative stress in male Wistar rats. Human and Experimental Toxicology, 32, 972–982.CrossRefPubMedGoogle Scholar
  7. 7.
    Chen, C., Jiang, X., Hu, Y., & Zhang, Z. (2013). The protective role of resveratrol in the sodium arsenite-induced oxidative damage via modulation of intracellular GSH homeostasis. Biological Trace Element Research, 155, 119–131.CrossRefPubMedGoogle Scholar
  8. 8.
    Abu El-Saad, A. M., Al-Kahtani, M. A., & Abdel-Moneim, A. M. (2016). N-acetylcysteine and meso-2,3-dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats. Drug Design, Development and Therapy, 10, 3425–3434.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Saha, S. S., & Ghosh, M. (2010). Ameliorative role of conjugated linolenic acid isomers against oxidative DNA damage induced by sodium arsenite in rat model. Food and Chemical Toxicology, 48, 3398–3405.CrossRefPubMedGoogle Scholar
  10. 10.
    Soong, Y.-Y., & Barlow, P. J. (2006). Quantification of gallic acid and ellagic acid from longan (Dimocarpus longan Lour.) seed and mango (Mangifera indica L.) kernel and their effects on antioxidant activity. Food Chemistry, 97, 524–530.CrossRefGoogle Scholar
  11. 11.
    Garcia-Nino, W. R., & Zazueta, C. (2015). Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection. Pharmacological Research, 97, 84–103.CrossRefPubMedGoogle Scholar
  12. 12.
    Doyle, B., & Griffiths, L. A. (1980). The metabolism of ellagic acid in the rat. Xenobiotica, 10, 247–256.CrossRefPubMedGoogle Scholar
  13. 13.
    Priyadarsini, K. I., Khopde, S. M., Kumar, S. S., & Mohan, H. (2002). Free radical studies of ellagic acid, a natural phenolic antioxidant. Journal of Agricultural and Food Chemistry, 50, 2200–2206.CrossRefPubMedGoogle Scholar
  14. 14.
    Pari, L., & Sivasankari, R. (2008). Effect of ellagic acid on cyclosporine A-induced oxidative damage in the liver of rats. Fundamental & Clinical Pharmacology, 22, 395–401.CrossRefGoogle Scholar
  15. 15.
    El-Shitany, N. A., El-Bastawissy, E. A., & El-desoky, K. (2014). Ellagic acid protects against carrageenan-induced acute inflammation through inhibition of nuclear factor kappa B, inducible cyclooxygenase and proinflammatory cytokines and enhancement of interleukin-10 via an antioxidant mechanism. International Immunopharmacology, 19, 290–299.CrossRefPubMedGoogle Scholar
  16. 16.
    Al-Kharusi, N., Babiker, H. A., Al-Salam, S., Waly, M. I., Nemmar, A., Al-Lawati, I., et al. (2013). Ellagic acid protects against cisplatin-induced nephrotoxicity in rats: A dose-dependent study. European Review for Medical and Pharmacological Sciences, 17, 299–310.PubMedGoogle Scholar
  17. 17.
    Yuce, A., Atessahin, A., Ceribasi, A. O., & Aksakal, M. (2007). Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats. Basic & Clinical Pharmacology & Toxicology, 101, 345–349.CrossRefGoogle Scholar
  18. 18.
    Gul, M., Aliosmanoglu, I., Uslukaya, O., Firat, U., Yuksel, H., Gumus, M., et al. (2013). The protective effect of ellagic acid on lung damage caused by experimental obstructive jaundice model. Acta Chirurgica Belgica, 113, 285–289.CrossRefPubMedGoogle Scholar
  19. 19.
    Al-Hasan, A. K. J. (2017). Effects of low-and high-level pulsed Nd: YAG laser irradiation on red blood cells and platelets indices of albino rats in vitro. Iraq Medical Journal, 1, 10–19.Google Scholar
  20. 20.
    Saha, S. S., & Ghosh, M. (2009). Comparative study of antioxidant activity of alpha-eleostearic acid and punicic acid against oxidative stress generated by sodium arsenite. Food and Chemical Toxicology, 47, 2551–2556.CrossRefPubMedGoogle Scholar
  21. 21.
    Celik, G., Semiz, A., Karakurt, S., Arslan, S., Adali, O., & Sen, A. (2013). A comparative study for the evaluation of two doses of ellagic acid on hepatic drug metabolizing and antioxidant enzymes in the rat. BioMed Research International, 2013, 358945.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Reitman, S., & Frankel, S. (1957). In vitro determination of transaminase activity in serum. American Journal of Clinical Pathology, 28, 56–63.CrossRefPubMedGoogle Scholar
  23. 23.
    Bishop, C., Chu, T., & Shihabi, Z. (1971). Single stable reagent for creatine kinase assay. Clinical Chemistry, 17, 548–550.PubMedGoogle Scholar
  24. 24.
    Whitaker, J. (1969). A general colorimetric procedure for the estimation of enzymes which are linked to the NADH/NAD + system. Clinica Chimica Acta, 24, 23–37.CrossRefGoogle Scholar
  25. 25.
    Ghosh, A., & Sil, P. C. (2008). A protein from Cajanus indicus Spreng protects liver and kidney against mercuric chloride-induced oxidative stress. Biological and Pharmaceutical Bulletin, 31, 1651–1658.CrossRefPubMedGoogle Scholar
  26. 26.
    Buege, J. A., & Aust, S. D. (1978). Microsomal lipid peroxidation. Methods Enzymology, 52, 302–310.CrossRefGoogle Scholar
  27. 27.
    Tracey, W. R., Linden, J., Peach, M. J., & Johns, R. A. (1990). Comparison of spectrophotometric and biological assays for nitric oxide (NO) and endothelium-derived relaxing factor (EDRF): Nonspecificity of the diazotization reaction for NO and failure to detect EDRF. Journal of Pharmacology and Experimental Therapeutics, 252, 922–928.PubMedGoogle Scholar
  28. 28.
    Jalaludeen, A. M., Lee, W. Y., Kim, J. H., Jeong, H. Y., Ki, K. S., Kwon, E. G., et al. (2015). Therapeutic efficacy of biochanin a against arsenic-induced renal and cardiac damage in rats. Environmental Toxicology and Pharmacology, 39, 1221–1231.CrossRefPubMedGoogle Scholar
  29. 29.
    Adil, M., Kandhare, A. D., Visnagri, A., & Bodhankar, S. L. (2015). Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: Decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α. Renal Failure, 37, 1396–1407.CrossRefPubMedGoogle Scholar
  30. 30.
    Dwivedi, N., Flora, G., Kushwaha, P., & Flora, S. J. (2014). Alpha-lipoic acid protects oxidative stress, changes in cholinergic system and tissue histopathology during co-exposure to arsenic-dichlorvos in rats. Environmental Toxicology and Pharmacology, 37, 7–23.CrossRefPubMedGoogle Scholar
  31. 31.
    Archer, S. (1993). Measurement of nitric oxide in biological models. The FASEB Journal, 7, 349–360.CrossRefPubMedGoogle Scholar
  32. 32.
    Priyamvada, S., Priyadarshini, M., Arivarasu, N., Farooq, N., Khan, S., Khan, S. A., et al. (2008). Studies on the protective effect of dietary fish oil on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Prostaglandins Leukotrienes and Essential Fatty Acids, 78, 369–381.CrossRefGoogle Scholar
  33. 33.
    Singh, K., Khanna, A., Visen, P., & Chander, R. (1999). Protective effect of ellagic acid on t-butyl hydroperoxide induced lipid peroxidation in isolated rat hepatocytes. Indian Journal of Experimental Biology, 37, 939–940.PubMedGoogle Scholar
  34. 34.
    Ding, Y., Zhang, B., Zhou, K., Chen, M., Wang, M., Jia, Y., et al. (2014). Dietary ellagic acid improves oxidant-induced endothelial dysfunction and atherosclerosis: Role of Nrf2 activation. International Journal of Cardiology, 175, 508–514.CrossRefPubMedGoogle Scholar
  35. 35.
    Song, L.-L., Tu, Y.-Y., Xia, L., Wang, W.-W., Wei, W., Ma, C.-M., et al. (2014). Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in k562 cells. PLoS ONE, 9, e104985.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Modi, M., Kaul, R. K., Kannan, G. M., & Flora, S. J. (2006). Co-administration of zinc and n-acetylcysteine prevents arsenic-induced tissue oxidative stress in male rats. Journal of Trace Elements in Medicine and Biology, 20, 197–204.CrossRefPubMedGoogle Scholar
  37. 37.
    Hemmati, A. A., Olapour, S., Varzi, H. N., Khodayar, M. J., Dianat, M., Mohammadian, B., and Yaghooti, H. (2017). Ellagic acid protects against arsenic trioxide-induced cardiotoxicity in rat. Human & Experimental Toxicology 960327117701986.Google Scholar
  38. 38.
    Ahad, A., Ganai, A. A., Mujeeb, M., & Siddiqui, W. A. (2014). Ellagic acid, an NF-κB inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chemico-Biological Interactions, 219, 64–75.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mehdi Goudarzi
    • 1
    • 2
  • Iman Fatemi
    • 3
    • 4
  • Amir Siahpoosh
    • 1
    • 5
  • Seyed Hashem Sezavar
    • 6
  • Esrafil Mansouri
    • 7
  • Saeed Mehrzadi
    • 8
    Email author
  1. 1.Medicinal Plant Research CenterAhvaz Jundishapur University of Medical SciencesAhvazIran
  2. 2.Student Research CommitteeAhvaz Jundishapur University of Medical SciencesAhvazIran
  3. 3.Department of Physiology and PharmacologyRafsanjan University of Medical SciencesRafsanjanIran
  4. 4.Physiology-Pharmacology Research CenterRafsanjan University of Medical SciencesRafsanjanIran
  5. 5.Department of Pharmacognosy, Faculty of PharmacyAhvaz Jundishapur University of Medical SciencesAhvazIran
  6. 6.Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology and MetabolismIran University of Medical SciencesTehranIran
  7. 7.Cellular and Molecular Research Center, Department of Anatomical Sciences, Faculty of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
  8. 8.Razi Drug Research CenterIran University of Medical SciencesTehranIran

Personalised recommendations