Advertisement

Cardiovascular Toxicology

, Volume 19, Issue 2, pp 105–119 | Cite as

An Overview on Arsenic Trioxide-Induced Cardiotoxicity

  • Vadavanath Prabhakaran VineethaEmail author
  • Kozhiparambil Gopalan Raghu
Article

Abstract

Arsenic trioxide (ATO) is among the first-line chemotherapeutic drugs used in oncological practice. It has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukaemia. The clinical use of ATO is hampered due to cardiotoxicity and hence many patients are precluded from receiving this highly effective treatment. An alternative to this would be to use any drug that can ameliorate the cardiotoxic effects and allow exploiting the full therapeutic potential of ATO, with considerable impact on cancer therapy. Generation of reactive oxygen species is involved in a wide range of human diseases, including cancer, cardiovascular, pulmonary and neurological disorders. Hence, agents with the ability to protect against these reactive species may be therapeutically useful. The present review focuses on the beneficial as well as harmful effects of arsenic and ATO, the mechanisms underlying ATO toxicity and the possible ways that can be adopted to circumvent ATO-induced toxicity.

Keywords

Arsenic trioxide Cardiotoxicity Reactive oxygen species Chemotherapy Phytochemicals 

Notes

Acknowledgements

The first author thank Kerala State Council for Science, Technology and Environment (KSCSTE), Woman Scientist Division (WSD) – Project Grant No.1107/2017/KSCSTE.

Compliance with Ethical Standards

Conflict of interest

There is no conflict of interest existing among the authors.

References

  1. 1.
    Fox, E., Razzouk, B. I., Widemann, B. C., Xiao, S., O’Brien, M., Goodspeed, W., Reaman, G. H., Blaney, S. M., Murgo, A. J., Balis, F. M., & Adamson, P. C. (2008). Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma. Blood, 111, 566–573.Google Scholar
  2. 2.
    Mathews, V., Chendamarai, E., George, B., Viswabandya, A., & Srivastava, A. (2011). Treatment of acute promyelocytic leukemia with single-agent arsenic trioxide. Mediterranean Journal of Hematology and Infectious Diseases, 3, e2011056.Google Scholar
  3. 3.
    Drolet, B., Simard, C., & Roden, D. M. (2004). Unusual effects of a QT-prolonging drug, arsenic trioxide, on cardiac potassium currents. Circulation, 109, 26–29.Google Scholar
  4. 4.
    Mumford, J. L., Wu, K., Xia, Y., Kwok, R., Yang, Z., Foster, J., & Sanders, W. E. (2007). Chronic arsenic exposure and cardiac repolarization abnormalities with QT interval prolongation in a population-based study. Environmental Health Perspectives, 115, 690–694.Google Scholar
  5. 5.
    Ducas, R. A., Seftel, M. D., Ducas, J., & Seifer, C. (2011). Monomorphic ventricular tachycardia caused by arsenic trioxide therapy for acute promyelocytic leukaemia. The Journal of the Royal College of Physicians of Edinburgh, 41, 117–118.Google Scholar
  6. 6.
    Costa, V. M., Carvalho, F., Duarte, J., Bastos, M. L., & Remião, F. (2013). The heart as a target for xenobiotic toxicity: The cardiac susceptibility to oxidative stress. Chemical Research in Toxicology, 26, 1285–1311.Google Scholar
  7. 7.
    Vineetha, V. P., Soumya, R. S., & Raghu, K. G. (2015). Phloretin ameliorates arsenic trioxide induced mitochondrial dysfunction in H9c2 cardiomyoblasts mediated via alterations in membrane permeability and ETC complexes. European Journal of Pharmacology, 754, 162–172.Google Scholar
  8. 8.
    Gupta, S., Das, B., & Sen, S. (2007). Cardiac hypertrophy: Mechanisms and therapeutic opportunities. Antioxidants & Redox Signaling, 9, 623–652.Google Scholar
  9. 9.
    Hughes, M. F., Beck, B. D., Chen, Y., Lewis, A. S., & Thomas, D. J. (2011). Arsenic exposure and toxicology: A historical perspective. Toxicological Sciences, 123, 305–332.Google Scholar
  10. 10.
    Cervantes, C., Ji, G., Ramirez, J. L., & Silver, S. (1994). Resistance to arsenic compounds in microorganisms. FEMS Microbiology Reviews, 15, 355–367.Google Scholar
  11. 11.
    European Food Safety Authority (EFSA) and EFSA Panel on Contaminants in the Food Chain (CONTAM). (2009). Scientific opinion on arsenic in food. EFSA Journal, 7, 199.Google Scholar
  12. 12.
    Smedley, P. L., & Kinniburgh, D. G. (2002). A review of the source, behaviour and distribution of arsenic in natural waters. Applied Geochemistry, 17, 517–568.Google Scholar
  13. 13.
    Lantz, R. C., & Hays, A. M. (2006). Role of oxidative stress in arsenic-induced toxicity. Drug Metabolism Reviews, 38, 791–804.Google Scholar
  14. 14.
    Schuhmacher-Wolz, U., Dieter, H. H., Klein, D., & Schneider, K. (2009). Oral exposure to inorganic arsenic: Evaluation of its carcinogenic and non-carcinogenic effects. Critical Reviews in Toxicology, 39, 271–298.Google Scholar
  15. 15.
    National Research Council (NRC). (1999). Arsenic in drinking water. Washington, DC: National Academy Press.Google Scholar
  16. 16.
    Chen, C. J., Chuang, Y. C., Lin, T. M., & Wu, H. Y. (1985). Malignant neoplasms among residents of a blackfoot disease endemic area in Taiwan: High arsenic artesian well water and cancers. Cancer Research, 45, 5895–5899.Google Scholar
  17. 17.
    Argos, M., Kalra, T., Rathouz, P. J., Chen, Y., Pierce, B., Parvez, F., Islam, T., Ahmed, A., Rakibuz-Zaman, M., Hasan, R., Sarwar, G., Slavkovich, V., van Geen, A., Graziano, J., & Ahsan, H. (2010). Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): A prospective cohort study. The Lancet, 376, 252–258.Google Scholar
  18. 18.
    Nordstrom, D. K. (2002). Public health. Worldwide occurrences of arsenic in ground water. Science, 296, 2143–2145.Google Scholar
  19. 19.
    International Agency for Cancer Research (IARC). (2004). Some drinking-water disinfectants and contaminants, including arsenic. In IARC monographs on the evaluation of carcinogenic risks to humans, Lyon: International Agency for Cancer Research (IARC), pp 39–267.Google Scholar
  20. 20.
    Smith, A. H., Lingas, E. O., & Rahman, M. (2000). Contamination of drinking-water by arsenic in Bangladesh: A public health emergency. Bulletin of the World Health Organization, 78, 1093–1103.Google Scholar
  21. 21.
    World Health Organisation (WHO) (1993). Guidelines for drinking-water quality. 2nd edn. Geneva: WHO, ISBN 924, p. 154460.Google Scholar
  22. 22.
    Environmental protection Agency (EPA). (2001). Natural primary drinking water regulations; Arsenic and clarifications to compliance and new source contaminants monitoring; proposed rule. Federal Register, 66(78), 20580.Google Scholar
  23. 23.
    Murgo, A. J. (2001). Clinical trials of arsenic trioxide in hematologic and solid tumors: Overview of the national cancer institute cooperative research and development studies. The Oncologist, 6, 22–28.Google Scholar
  24. 24.
    Shibata, T., Solo-Gabriele, H. M., Fleming, L. E., Cai, Y., & Townsend, T. G. (2007). A mass balance approach for evaluating leachable arsenic and chromium from an inservice CCA-treated wood structure. Science of the Total Environment, 372, 624–635.Google Scholar
  25. 25.
    Smith, A. H., Hopenhayn-Rich, C., Bates, M. N., Goeden, H. M., Hertz-Picciotto, I., Duggan, H. M., Wood, R., Kosnett, M. J., & Smith, M. T. (1992). Cancer risks from arsenic in drinking water. Environmental Health Perspectives, 97, 259–267.Google Scholar
  26. 26.
    Greider, C. W. (1996). Telomere length regulation. Annual Review of Biochemistry, 65, 337–365.Google Scholar
  27. 27.
    Chou, W. C., Hawkins, A. L., Barrett, J. F., Griffin, C. A., & Dang, C. V. (2001). Arsenic inhibition of telomerase transcription leads to genetic instability. Journal of Clinical Investigation, 108, 1541–1547.Google Scholar
  28. 28.
    Bryan, T. M., Englezou, A., Gupta, J., Bacchetti, S., & Reddel, R. R. (1995). Telomere elongation in immortal human cells without detectable telomerase activity. EMBO Journal, 14, 4240–4248.Google Scholar
  29. 29.
    Gallagher, R. E. (1998). Arsenic: New life for an old potion. New England Journal of Medicine, 339, 1389–1391.Google Scholar
  30. 30.
    Shim, M. J., Kim, H. J., Yang, S. J., Lee, I. S., Choi, H. I., & Kim, T. (2002). Arsenic trioxide induces apoptosis in chronic myelogenous leukemia K562 cells: Possible involvement of p38 MAP kinase. Journal of Biochemistry and Molecular Biology, 35, 377–383.Google Scholar
  31. 31.
    Florea, A. M. (2005). Toxicity of alkylated derivatives of arsenic, antimony and tin: Cellular uptake, cytotoxicity, genotoxic effects, perturbation of Ca 2+ homeostasis and cell death. Aachen: Shaker Verlag.Google Scholar
  32. 32.
    Griffin, R. J., Williams, B. W., Park, H. J., & Song, C. W. (2005). Preferential action of arsenic trioxide in solid-tumour microenvironment enhances radiation therapy. International Journal of Radiation Oncology Biology Physics, 61, 1516–1522.Google Scholar
  33. 33.
    Florea, A. M., & Büsselberg, D. (2006). Metals and metal compounds: Occurrence, use, benefits and toxic cellular effects. BioMetals, 19, 419–427.Google Scholar
  34. 34.
    Ratnaike, R. N. (2003). Acute and chronic arsenic toxicity. Postgraduate Medical Journal, 79, 391–396.Google Scholar
  35. 35.
    Antman, K. H. (2001). Introduction: The history of arsenic trioxide in cancer therapy. The Oncologist, 6, 1–2.Google Scholar
  36. 36.
    Chen, C. J., Hsueh, Y. M., Lai, M. S., Shyu, M. P., Chen, S. Y., Wu, M. M., Kuo, T. L., & Tai, T. Y. (1995). Increased prevalence of hypertension and long-term arsenic exposure. Hypertension, 25, 53–60.Google Scholar
  37. 37.
    Tallman, M. S. (2007). Treatment of relapsed or refractory acute promyelocytic leukemia. Best Practice & Research Clinical Haematology, 20, 57–65.Google Scholar
  38. 38.
    Platanias, L. C. (2009). Biological responses to arsenic compounds. Journal of Biological Chemistry, 284, 18583–18587.Google Scholar
  39. 39.
    Iland, H. J., & Seymour, J. F. (2013). Role of arsenic trioxide in acute promyelocytic leukemia. Current Treatment Options in Oncology, 14, 170–184.Google Scholar
  40. 40.
    Mi, J. (2011). Current treatment strategy of acute promyelocytic leukemia. Frontiers in Medicine, 5, 341–347.Google Scholar
  41. 41.
    Baj, G., Arnulfo, A., Deaglio, S., Mallone, R., Vigone, A., De Cesaris, M. G., Surico, N., Malavasi, F., & Ferrero, E. (2002). Arsenic trioxide and breast cancer: Analysis of the apoptotic, differentiative and immunomodulatory effects. Breast Cancer Research and Treatment, 73, 61–73.Google Scholar
  42. 42.
    de The, H., Chomienne, C., Lanotte, M., Degos, L., & Dejean, A. (1990). The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature, 347, 558–561.Google Scholar
  43. 43.
    Borrow, J., Goddard, A. D., Sheer, D., & Solomon, E. (1990). Molecular analysis of acute promyelocytic leukemia break point cluster region on chromosome 17. Science, 249, 1577–1580.Google Scholar
  44. 44.
    Dyck, J. A., Maul, G. G., Miller, W. H. Jr., Chen, J. D., Kakizuka, A., & Evans, R. M. (1994). A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell, 76, 333–343.Google Scholar
  45. 45.
    Mu, Z. M., Chin, K. V., Liu, J. H., Lozano, G., & Chang, K. S. (1994). PML, a growth suppressor disrupted in acute promyelocytic leukemia. Molecular and Cellular Biology, 14, 6858–6867.Google Scholar
  46. 46.
    Chang, K. S., Fan, Y. H., Andreeff, M., Liu, J., & Mu, Z. M. (1995). The PML gene encodes a phosphoprotein associated with the nuclear matrix. Blood, 85, 12.Google Scholar
  47. 47.
    Shao, W., Fanelli, M., Ferrara, F. F., Riccioni, R., Rosenauer, A., Davison, K., Lamph, W. W., Waxman, S., Pelicci, P. G., Lo Coco, F., Avvisati, G., Testa, U., Peschle, C., Gambacorti-Passerini, C., Nervi, C., & Miller, W. H. J. (1998). Arsenic trioxide as an inducer of apoptosis and loss of PML/RAR alpha protein in acute promyelocytic leukemia cells. Journal of the National Cancer Institute (1988), 90, 124–133.Google Scholar
  48. 48.
    Zhang, X. W., Yan, X. J., Zhou, Z. R., Yang, F. F., Wu, Z. Y., Sun, H. B., Liang, W. X., Song, A. X., Lallemand-Breitenbach, V., Jeanne, M., Zhang, Q. Y., Yang, H. Y., Huang, Q. H., Zhou, G. B., Tong, J. H., Zhang, Y., Wu, J. H., Hu, H. Y., deThe, H., Chen, S. J., & Chen, Z. (2010). Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science, 328, 240–243.Google Scholar
  49. 49.
    Mi, J.-Q., Li, J.-M., Shen, Z.-X., Chen, S.-J., & Chen, Z. (2012). How to manage acute promyelocytic leukemia. Leukemia, 26, 1743–1751.Google Scholar
  50. 50.
    Sun, H. D. M. L., Hu, X. C., & Zhang, T. D. (1992). Thirty two cases of treating acute promyelocytic leukemia by Ailing I therapy combined with syndrome differentiation treatment of traditional Chinese medicine. Chinese Journal Combinat Traditional Chinese Medicine West Medicine, 1996, 170–171.Google Scholar
  51. 51.
    Zhang, P. (1999). The use of arsenic trioxide in the treatment of acute promyelocytic leukemia. Journal of Biological Regulators and Homeostatic Agents, 13, 195–200.Google Scholar
  52. 52.
    Soignet, S. L., Frankel, S. R., Douer, D., Tallmann, M. S., Kantarjian, H., Calleja, E., Stone, R. M., Kalaycio, M., Scheinberg, D. A., Steinherz, P., Sievers, E. L., Coutre, S., Dahlberg, S., Ellison, R., & Warrell, R. P. Jr. (2001). United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. Journal of Clinical Oncology, 19, 3852–3860.Google Scholar
  53. 53.
    Fenaux, P., Chomienne, C., & Degos, L. (2001). Treatment of acute promyelocytic leukaemia. Best Practice & Research: Clinical Haematology, 14, 153–174.Google Scholar
  54. 54.
    Zhu, J., Chen, Z., Lallemand-Breitenbach, V., & de The, H. (2002). How acute promyelocytic leukaemia revived arsenic. Nature Reviews Cancer, 2, 705–713.Google Scholar
  55. 55.
    Chen, C. J., Chiou, H. Y., Chiang, M. H., Lin, L. J., & Tai, T. Y. (1996). Dose-response relationship between ischemic heart disease mortality and long-term arsenic exposure. Arteriosclerosis, Thrombosis, and Vascular Biology, 16, 504–510.Google Scholar
  56. 56.
    Abaza, Y., Kantarjian, H., Garcia-Manero, G., Estey, E., Borthakur, G., Jabbour, E., Faderl, S., O’Brien, S., Wierda, W., Pierce, S., Brandt, M., McCue, D., Luthra, R., Patel, K., Kornblau, S., Kadia, T., Daver, N., DiNardo, C., Jain, N., Verstovsek, S., Ferrajoli, A., Andreeff, M., Konopleva, M., Estrov, Z., Foudray, M., McCue, D., Cortes, J., & Ravandi, F. (2017). Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood, 129, 1275–1283.Google Scholar
  57. 57.
    Hosseini, R., Mandegary, A., Alimoghaddam, K., Ghavamzadeh, A., & Ghahremani, M. H. (2008). Pharmacokinetic of arsenic trioxide in newly diagnosed acute promyelocytic leukemia patients. Journal of Applied Sciences, 8, 4617–4623.Google Scholar
  58. 58.
    Shen, Y., Shen, Z. X., Yan, H., Chen, J., Zeng, X. Y., Li, J. M., Li, X. S., Wu, W., Xiong, S. M., Zhao, W. L., Tang, W., Wu, F., Liu, Y. F., Niu, C., Wang, Z. Y., Chen, S. J., & Chen, Z. (2001). Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: A comparison with conventional dosage. Leukemia, 15, 735–741.Google Scholar
  59. 59.
    Wang, Z., Zhou, J., Lu, X., Gong, Z., & Le, X. C. (2004). Arsenic speciation in urine from acute promyelocytic leukemia patients undergoing arsenic trioxide treatment. Chemical Research in Toxicology, 17, 95–103.Google Scholar
  60. 60.
    Fukai, Y., Hirata, M., Ueno, M., Ichikawa, N., Kobayashi, H., Saitoh, H., Sakurai, T., Kinoshita, K., Kaise, T., & Ohta, S. (2006). Clinical pharmacokinetic study of arsenic trioxide in an acute promyelocytic leukemia (APL) patient: Speciation of arsenic metabolites in serum and urine. Biological & and Pharmaceutical Bulletin, 29, 1022–1027.Google Scholar
  61. 61.
    Fowler, B. A., Chou, S. J., Jones, R. L., & Chen, C. J. (2007). Arsenic. In G. F. Nordberg, B. A. Fowler, M. Nordberg, L. T. Freiberg (Eds.), Handbook on the toxicology of metals (pp. 367–443). Amsterdam: Elsevier.Google Scholar
  62. 62.
    Shen, Z. X., Chen, G. Q., Ni, J. H., Li, X. S., Xiong, S. M., Qiu, Q. Y., Zhu, J., Tang, W., Sun, G. L., Yang, K. Q., Chen, Y., Zhou, L., Fang, Z. W., Wang, Y. T., Ma, J., Zhang, P., Zhang, T. D., Chen, S. J., Chen, Z., & Wang, Z. Y. (1997). Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood, 89, 3354–3360.Google Scholar
  63. 63.
    Ni, J., Chen, G., Shen, Z., Li, X., Liu, H., Huang, Y., Fang, Z., Chen, S., Wang, Z., & Chen, Z. (1998). Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia. Chinese Medical Journal, 111, 1107–1110.Google Scholar
  64. 64.
    Hua, H., Qin, S., Rui, J., & Li, J. (2011). Pharmacokinetics of arsenic trioxide (As2O3) in Chinese primary hepatocarcinoma patients. Asian Pacific Journal of Cancer Prevention, 12, 61–65.Google Scholar
  65. 65.
    Schoen, A., Beck, B., Sharma, R., & Dube, E. (2004). Arsenic toxicity at low doses: Epidemiological and mode of action considerations. Toxicology and Applied Pharmacology, 198, 253–267.Google Scholar
  66. 66.
    Singh, A. P., Goel, R. K., & Kaur, T. (2011). Mechanisms pertaining to arsenic toxicity. International Journal of Toxicology, 18, 87–93.Google Scholar
  67. 67.
    Miller, W. H., Schipper, H. M., Lee, J. S., Singer, J., & Waxman, S. (2002). Mechanisms of action of arsenic trioxide. Cancer Research, 62, 3893–3903.Google Scholar
  68. 68.
    Lau, A. T., Li, M., Xie, R., He, Q. Y., & Chiu, J. F. (2004). Opposed arsenite-induced signalling pathways promote cell proliferation or apoptosis in cultured lung cells. Carcinogenesis, 25, 21–28.Google Scholar
  69. 69.
    Benbrahim-Tallaa, L., Webber, M. M., & Waalkes, M. P. (2007). Mechanisms of acquired androgen independence during arsenic-induced malignant trans-formation of human prostate epithelial cells. Environmental Health Perspectives, 115, 243–247.Google Scholar
  70. 70.
    Chen, H., Liu, J., Zhao, C. Q., Diwan, B. A., Merrick, B. A., & Waalkes, M. P. (2001). Association of c-myc overexpression and hyperproliferation with arsenite-induced malignant transformation. Toxicology and Applied Pharmacology, 175, 260–268.Google Scholar
  71. 71.
    Benbrahim-Tallaa, L., Webber, M. M., & Waalkes, M. P. (2005). Acquisition of androgen independence by human prostate epithelial cells during arsenic-induced malignant transformation. Environmental Health Perspectives, 113, 1134–1139.Google Scholar
  72. 72.
    Kitchin, K. T. (2001). Recent advances in arsenic carcinogenesis: Modes of action, animal model systems, and methylated arsenic metabolites. Toxicology and Applied Pharmacology, 172, 249–261.Google Scholar
  73. 73.
    Zhao, C. Q., Young, M. R., Diwan, B. A., Coogan, T. P., & Waalkes, M. P. (1997). Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proceedings of the National Academy of Sciences of the United States of America, 94, 10907–10912.Google Scholar
  74. 74.
    Jensen, T. J., Novak, P., Eblin, K. E., Gandolfi, A. J., & Futscher, B. W. (2008). Epigenetic remodeling during arsenical-induced malignant transformation. Carcinogenesis, 29, 1500–1508.Google Scholar
  75. 75.
    Chow, S. K., Chan, J. Y., & Fung, K. P. (2004). Suppression of cell proliferation and regulation of estrogen receptor alpha signalling pathway by arsenic trioxide on human breast cancer MCF-7 cells. Journal of Endocrinology, 182, 325–337.Google Scholar
  76. 76.
    Chen, G. C., Guan, L. S., Hu, W. L., & Wang, Z. Y. (2002). Functional repression of estrogen receptor a by arsenic trioxide in human breast cancer cells. Anticancer Research, 22, 633–638.Google Scholar
  77. 77.
    Roboz, G. J., Dias, S., Lam, G., Lane, W. J., Soignet, S. L., Warrell, R. P., & Rafii, S. (2000). Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood, 96, 1523–1530.Google Scholar
  78. 78.
    Qian, Y., Castranova, V., & Shi, X. (2003). New perspectives in arsenic-induced cell signal transduction. Journal of Inorganic Biochemistry, 96, 271–278.Google Scholar
  79. 79.
    Barbey, J. T., & Soignet, S. (2001). Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia. Annals of Internal Medicine, 135, 842–843.Google Scholar
  80. 80.
    Westervelt, P., Brown, R. A., Adkins, D. R., Khoury, H., Curtin, P., Hurd, D., Luger, S. M., Ma, M. K., Ley, T. J., & DiPersio, J. F. (2001). Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide. Blood, 98, 266–271.Google Scholar
  81. 81.
    Ning, Y., Shen, Q., Herrick, K., Mikkelsen, R., Anscher, M., Houlihan, R., & Lapane, K. (2012). Abstract LB-339: Cause of death in cancer survivors. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research, 72(8) (Suppl. 1).  https://doi.org/10.1158/1538-7445.AM2012-LB-339.
  82. 82.
    Driver, J. A., Djousse´, L., Logroscino, G., Gaziano, J. M., & Kurth, T. (2008). Incidence of cardiovascular disease and cancer in advanced age: Prospective cohort study. The BMJ 337, a2467.Google Scholar
  83. 83.
    Albini, A., Pennesi, G., Donatelli, F., Cammarota, R., De Flora, S., & Noonan, D. M. (2010). Cardiotoxicity of anticancer drugs: The need for cardio-oncology and cardio-oncological prevention. Journal of the National Cancer Institute (1988), 102, 14–25.Google Scholar
  84. 84.
    Bovelli, D., Plataniotis, G., Roila, F.,& On behalf of the ESMO Guidelines Working Group (2010). Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO clinical practice guidelines. Annals of Oncology 21, v277–v282.Google Scholar
  85. 85.
    Morganroth, J., Brozovich, F. V., McDonald, J. T., & Jacobs, R. A. (1991). Variability of the QT measurement in healthy men, with implications for selection of an abnormal QT value to predict drug toxicity and proarrhythmia. American Journal of Cardiology, 67, 774–776.Google Scholar
  86. 86.
    Unnikrishnann, D., Dutcher, J. P., Varshneya, N., Lucariello, R., Api, M., Garl, S., Wiernik, P. H., & Chiaramida, S. (2001). Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide. Blood, 97, 1514–1516.Google Scholar
  87. 87.
    Ficker, E., Kuryshev, Y. A., Dennis, A. T., Obejero-Paz, C., Wang, L., Hawryluk, P., Wible, B. A., & Brown, A. M. (2004). Mechanisms of arsenic-induced prolongation of cardiac repolarization. Molecular Pharmacology, 66, 33–44.Google Scholar
  88. 88.
    Clancy, C. E., Kurokawa, J., Tateyama, M., Wehrens, X. H. T., & Kass, R. S. (2003). K+ channel structure-activity relationships and mechanisms of drug-induced QT prolongation. Annual Review of Pharmacology and Toxicology, 43, 441–461.Google Scholar
  89. 89.
    Taglialatela, M., Castaldo, P., Iossa, S., Pannaccione, A., Fresi, A., Ficker, E., & Annunziato, L. (1997). Regulation of the human ether-a-go go related gene (HERG) K+ channels by reactive oxygen species. Proceedings of the National Academy of Sciences of the United States of America, 94, 11698–11703.Google Scholar
  90. 90.
    Berube, J., Caouette, D., & Daleau, P. (2001). Hydrogen peroxide modifies the kinetics of HERG channel expressed in a mammalian cell line. Journal of Pharmacology and Experimental Therapeutics, 297, 96–102.Google Scholar
  91. 91.
    Roden, D. M., & Viswanathan, P. C. (2005). Genetics of acquired long QT syndrome. Journal of Clinical Investigation, 115, 2025–2032.Google Scholar
  92. 92.
    van Noord, C., Eijgelsheim, M., & Stricker, B. H. (2010). Drug- and non-drug-associated QT interval prolongation. British Journal of Clinical Pharmacology, 70, 16–23.Google Scholar
  93. 93.
    Ott, M., Gogvadze, V., Orrenius, S., & Zhivotovsky, B. (2007). Mitochondria, oxidative stress and cell death. Apoptosis, 12, 913–922.Google Scholar
  94. 94.
    Rana, S. V. (2008). Metals and apoptosis: Recent developments. Journal of Trace Elements in Medicine and Biology, 22, 262–284.Google Scholar
  95. 95.
    Young, I., & Woodside, J. (2001). Antioxidants in health and disease. Journal of Clinical Pathology, 54, 176–186.Google Scholar
  96. 96.
    Willcox, J. K., Ash, S. L., & Catignani, G. L. (2004). Antioxidants and prevention of chronic disease. Critical Reviews in Food Science and Nutrition, 44, 275–295.Google Scholar
  97. 97.
    Fang, Y. Z. (2002). Free radicals and nutrition. In Y. Z. Fang, Zheng & RL (Eds.), Theory and application of free radical biology (p. 647). Beijing: Scientific Press.Google Scholar
  98. 98.
    Shi, H., Hudson, L. G., Ding, W., Wang, S., Cooper, K. L., Liu, S., Chen, Y., Shi, X., & Liu, K. J. (2004). Arsenite causes DNA damage in keratinocytes via generation of hydroxyl radicals. Chemical Research in Toxicology, 17, 871–878.Google Scholar
  99. 99.
    Woo, S. H., Park, I. C., Park, M. J., Lee, H. C., Lee, S. J., Chun, Y. J., Lee, S. H., Hong, S. I., & Rhee, C. H. (2002). Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells. International Journal of Oncology, 21, 57–63.Google Scholar
  100. 100.
    Han, Y. H., Moon, H. J., You, B. R., Kim, S. Z., Kim, S. H., & Park, W. H. (2010). Effects of arsenic trioxide on cell death, reactive oxygen species and glutathione levels in different cell types. International Journal of Molecular Medicine, 25, 121–128.Google Scholar
  101. 101.
    Sun, Y., Wang, C., Wang, L., Dai, Z., & Yang, K. (2018). Arsenic trioxide induces apoptosis and the formation of reactive oxygen species in rat glioma cells. Cellular & Molecular Biology Letters, 23, 13.Google Scholar
  102. 102.
    Hagen, T. M., Wehr, C. M., & Ames, B. N. (1998). Mitochondrial decay in aging. Reversal through supplementation of acetyl-Lcarnitine and N-tert-butyl-alpha-phenyl-nitrone. Annals of the New York Academy of Sciences, 854, 214–223.Google Scholar
  103. 103.
    Bahorun, T., Soobratte, M. A., Luximon-Ramma, V., & Aruoma, O. I. (2006). Free radicals and antioxidants in cardiovascular health and disease. Internet Journal of Medical Update, 1, 25–41.Google Scholar
  104. 104.
    Cadenas, E., & Davies, K. J. A. (2000). Mitocondrial free radical generation, oxidative stress, and aging. Free Radical Biology and Medicine, 29, 222–230.Google Scholar
  105. 105.
    Mieyal, J. J., Gallogly, M. M., Qanungo, S., Sabens, E. A., & Shelton, M. D. (2008). Molecular mechanisms and clinical implications of reversible protein s-glutathionylation. Antioxidants & Redox Signaling, 10, 1941–1988.Google Scholar
  106. 106.
    Anderson, T. J., Meredith, I. T., Yeung, A. C., Frei, B., Selwyn, A. P., & Ganz, P. (1995). The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. New England Journal of Medicine, 332, 488–493.Google Scholar
  107. 107.
    Guzik, T. J., West, N. E. J., Black, E., McDonald, D., Ratnatunga, C., Pillai, R., & Channon, K. M. (2000). Vascular superoxide production by NAD(P)H oxidase: Association with endothelial dysfunction and clinical risk factors. Circulation Research, 86, e85–e90.Google Scholar
  108. 108.
    Heymes, C., Bendall, J. K., Ratajczak, P., Cave, A. C., Samuel, J. L., Hasenfuss, G., & Shah, A. M. (2003). Increased myocardial NADPH oxidase activity in human heart failure. Journal of the American College of Cardiology, 41, 2164–2171.Google Scholar
  109. 109.
    Halliwell, B. (2011). Free radicals and antioxidants-quo vadis? Trends in Pharmacological Sciences, 32, 125–130.Google Scholar
  110. 110.
    Chance, B., Sies, H., & Boveris, A. (1979). Hydroperoxide metabolism in mammalian organs. Physiological Reviews, 59, 527–605.Google Scholar
  111. 111.
    Hwang, J. T., Kwon, D. Y., Park, O. J., & Kim, M. S. (2008). Resveratrol protects ROS-induced cell death by activating AMPK in H9c2 cardiac muscle cells. Genes & Nutrition, 2, 323–326.Google Scholar
  112. 112.
    Gomes, E. C., Silva, A. N., & de Oliveira, M. R. (2012). Oxidants, antioxidants, and the beneficial roles of exercise-induced production of reactive species. Oxidative Medicine and Cellular Longevity, 2012, 12.Google Scholar
  113. 113.
    Ursini, F., Maiorino, M., & Brigelius-Flohé, R. (1995). The diversity of glutathione peroxidase. Methods in Enzymology, 252, 38–63.Google Scholar
  114. 114.
    Vineetha, V. P., Girija, S., Soumya, R. S., & Raghu, K. G. (2014). Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity. Food & Function, 5, 502–511.Google Scholar
  115. 115.
    Brookes, P. S., Yoon, Y., Robotham, J. L., Anders, M. W., & Sheu, S. S. (2004). Calcium, ATP, and ROS: A mitochondrial love-hate triangle. American Journal of Physiology. Cell Physiology, 287, 817–833.Google Scholar
  116. 116.
    Yano, M., Ikeda, Y., & Matsuzaki, M. (2005). Altered intracellular Ca2+ handling in heart failure. Journal of Clinical Investigation, 115, 556–564.Google Scholar
  117. 117.
    Berridge, M. J., Lipp, P., & Bootman, M. D. (2000). The versatility and universality of calcium signalling. Nature Reviews Molecular Cell Biology, 1, 11–21.Google Scholar
  118. 118.
    Orrenius, S., Zhivotovsky, B., & Nicotera, P. (2003). Regulation of cell death: The calcium-apoptosis link. Nature Reviews Molecular Cell Biology, 4, 552–565.Google Scholar
  119. 119.
    Berridge, M. J., Bootman, M. D., & Roderick, H. L. (2003). Calcium signalling: Dynamics, homeostasis and remodelling. Nature Reviews Molecular Cell Biology, 4, 517–529.Google Scholar
  120. 120.
    Rizzuto, R., Brini, M., Murgia, M., & Pozzan, T. (1993). Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighbouring mitochondria. Science, 262, 744–747.Google Scholar
  121. 121.
    Wang, Y., & Goldhaber, J. I. (2004). Return of calcium: Manipulating intracellular calcium to prevent cardiac pathologies. Proceedings of the National Academy of Sciences of the United States of America, 101, 5697–5698.Google Scholar
  122. 122.
    Sitsapesan, R., & Williams, A. J. (2000). Do inactivation mechanisms rather than adaptation hold the key to understanding ryanodine receptor channel gating? Journal of General Physiology, 116, 867–872.Google Scholar
  123. 123.
    Eisner, D. A., Trafford, A. W., Diaz, M. E., Overend, C. L., & O’Neill, S. C. (1998). The control of Ca release from the cardiac sarcoplasmic reticulum: Regulation versus autoregulation. Cardiovascular Research, 38, 589–604.Google Scholar
  124. 124.
    Florea, A. M., Yamoah, E. N., & Dopp, E. (2005). Intracellular calcium disturbances induced by arsenic and its methylated derivatives in relation to genomic damage and apoptosis induction. Environmental Health Perspectives, 113, 659–664.Google Scholar
  125. 125.
    Zhang, J., Sun, G., Wang, M., Liao, P., Du, Y., Yang, K., & Sun, X. (2016). Arsenic trioxide triggered calcium homeostasis imbalance and induced endoplasmic reticulum stress-mediated apoptosis in adult rat ventricular myocytes. Toxicology Research, 5, 682–688.Google Scholar
  126. 126.
    Ohnishi, K., Yoshida, H., Shigeno, K., Nakamura, S., Fujisawa, S., Naito, K., Shinjo, K., Fujita, Y., Matsui, H., & Takeshita, A. (2000). Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia. Annals of Internal Medicine, 133, 881–885.Google Scholar
  127. 127.
    Yedjou, C. G., & Tchouwou, P. B. (2007). In-vitro cytotoxic and genotoxic effects of arsenic trioxide on human leukemia (HL-60) cells using the MTT and alkaline single cell electrophoresis (comet) assays. Molecular and Cellular Biochemistry, 301, 123–130.Google Scholar
  128. 128.
    Michel, L., Dupuy, A., Jean-Louis, F., Sors, A., Poupon, J., Viguier, M., Musette, P., Dubertret, L., Degos, L., Dombret, H., & Bachelez, H. (2003). Arsenic trioxide induces apoptosis of cutaneous T cell lymphoma cells: Evidence for a partially caspase-independent pathway and potentiation by ascorbic acid (vitamin C). The Journal of Investigative Dermatology, 121, 881–893.Google Scholar
  129. 129.
    Huang, H. S., Chang, W. C., & Chen, C. J. (2002). Involvement of reactive oxygen species in arsenite-induced down regulation of phospholipid hydroperoxide glutathione peroxidase in human epidermoid carcinoma A431 cells. Free Radical Biology and Medicine, 33, 864–873.Google Scholar
  130. 130.
    Graham-Evans, B., Cohly, H. H. P., Yu, H., & Tchounwou, P. B. (2004). Arsenic-induced genotoxic and cytotoxic effects in human keratinocytes, melanocytes and dendritic cells. International Journal of Environmental Research and Public Health, 1, 83–89.Google Scholar
  131. 131.
    Waclavicek, M., Berer, A., Oehler, L., Stöckl, J., Schloegl, E., Majdic, O., & Knapp, W. (2001). Calcium ionophore: A single reagent for the differentiation of primary human acute myelogenous leukaemia cells towards dendritic cells. British Journal of Haematology, 114, 466–473.Google Scholar
  132. 132.
    Parag, H. A., Raboy, B., & Kulka, R. G. (1987). Effects of heat shock on protein degradation in mammalian cells involvement of the ubiquitin system. EMBO Journal, 6, 55–61.Google Scholar
  133. 133.
    Matsui, M., Nishigori, C., Toyokuni, S., Takada, J., Akaboshi, M., Ishikawa, M., Imamura, S., & Miyachi, Y. (1999). The role of oxidative DNA damage in human arsenic carcinogenesis: Detection of 8-hydroxy-2′- deoxyguanosine in arsenic-related Bowen’s disease. The Journal of Investigative Dermatology, 113, 26–31.Google Scholar
  134. 134.
    Alarifi, S., Ali, D., Alkahtani, S., Siddiqui, M. A., & Ali, B. A. (2013). Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells. OncoTargets and Therapy, 6, 75–84.Google Scholar
  135. 135.
    Nordenson, I., & Beckman, L. (1991). Is the genotoxic effect of arsenic mediated by oxygen free radicals? Human Heredity, 41, 71–73.Google Scholar
  136. 136.
    Barchowsky, A., Klei, L. R., Dudek, E. J., Swartz, H. M., & James, P. E. (1999). Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radical Biology and Medicine, 27, 1405–1412.Google Scholar
  137. 137.
    Smith, K. R., Klei, L. R., & Barchowsky, A. (2001). Arsenite stimulates plasma membrane NADPH oxidase in vascular endothelial cells. American Journal of Physiology-Lung Cellular and Molecular Physiology, 280, L442–L449.Google Scholar
  138. 138.
    Bunderson, M., Brooks, D. M., Walker, D. L., Rosenfeld, M. E., Coffin, J. D., & Beall, H. D. (2004). Arsenic exposure exacerbates atherosclerotic plaque formation and increases nitrotyrosine and leukotriene biosynthesis. Toxicology and Applied Pharmacology, 201, 32–39.Google Scholar
  139. 139.
    Lee, P. C., Ho, I. C., & Lee, T. C. (2005). Oxidative stress mediates sodium arsenite-induced expression of heme oxygenase-1, monocyte chemoattractant protein-1, and interleukin-6 in vascular smooth muscle cells. Toxicological Sciences, 85, 541–550.Google Scholar
  140. 140.
    Pysher, M. D., Chen, Q. M., & Vaillancourt, R. R. (2008). Arsenic alters vascular smooth muscle cell focal adhesion complexes leading to activation of FAK-src mediated pathways. Toxicology and Applied Pharmacology, 231, 135–141.Google Scholar
  141. 141.
    Tsai, S. H., Hsieh, M. S., Chen, L., Liang, Y. C., Lin, J. K., & Lin, S. Y. (2001). Suppression of Fas ligand expression on endothelial cells by arsenite through reactive oxygen species. Toxicology Letters, 123, 11–19.Google Scholar
  142. 142.
    Chen, S. C., Tsai, M. H., Wang, H. J., Yu, H. S., & Chang, L. W. (2007). Involvement of substance P and neurogenic inflammation in arsenic-induced early vascular dysfunction. Toxicological Sciences, 95, 82–88.Google Scholar
  143. 143.
    Pereira, F. E., Coffin, J. D., & Beall, H. D. (2007). Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite-potential mechanism in the development of atherosclerosis. Toxicology and Applied Pharmacology, 220, 164–177.Google Scholar
  144. 144.
    Tsou, T. C., Tsai, F. Y., Hsieh, Y. W., Li, L. A., Yeh, S. C., & Chang, L. W. (2005). Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase. Toxicology and Applied Pharmacology, 208, 277–284.Google Scholar
  145. 145.
    Balakumar, P., & Kaur, J. (2009). Arsenic exposure and cardiovascular disorders: An overview. Cardiovascular Toxicology, 9, 169–176.Google Scholar
  146. 146.
    Lee, M. Y., Lee, Y. H., Lim, K. M., Chung, S. M., Bae, O. N., Kim, H., Lee, C. R., Park, J. D., & Chung, J. H. (2005). Inorganic arsenite potentiates vasoconstriction through calcium sensitization in vascular smooth muscle. Environmental Health Perspectives, 113, 1330–1335.Google Scholar
  147. 147.
    Raghu, K. G., & Cherian, O. L. (2009). Characterization of cytotoxicity induced by arsenic trioxide (a potent anti-APL drug) in rat cardiac myocytes. Journal of Trace Elements in Medicine and Biology, 23, 61–68.Google Scholar
  148. 148.
    Zhao, J. L., Sun, B. G., Wen, Q. Z., Zhang, J. J., Jin, W., Xue, J. X., & Zhuang, W. Y. (2007). Effect of early and non-early controlled-release of arsenic-trioxide eluting stents on restenosis inhibition in a canine model. Zhonghua Xin Xue Guan Bing Za Zhi, 35, 571–574.Google Scholar
  149. 149.
    Gill, C., Mestril, R., & Sali, A. (2002). Losing heart; The role of apoptosis in heart disease-noval therapeutic target. The FASEB Journal, 16, 135–146.Google Scholar
  150. 150.
    Nerheim, P., Krishnan, S. C., Olshansky, B., & Shivkumar, K. (2001). Apoptosis in the genesis of cardiac rhythm disorders. Cardiology Clinics, 19, 155–163.Google Scholar
  151. 151.
    James, T. N. (1996). Long reflections on the QT interval: The sixth annual Gordon K. Moe Lecture. Journal of Cardiovascular Electrophysiology, 7, 738–759.Google Scholar
  152. 152.
    Best, P. J., Hasdai, D., Sangiorgi, G., Schwartz, R. S., Holmes, D. R. Jr., & Simari, R. D. (1999). Apoptosis. Basic concepts and implications in coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 19, 14–22.Google Scholar
  153. 153.
    Jacobson, M. D. (1996). Reactive oxygen species and programmed cell death. Trends in Biochemical Sciences, 21, 83–86.Google Scholar
  154. 154.
    Zhao, X., Feng, T., Chen, H., Shan, H., Zhang, Y., Lu, Y., & Yang, B. (2008). Arsenic trioxide-induced apoptosis in H9c2 cardiomyocytes: Implications in cardiotoxicity. Basic & Clinical Pharmacology & Toxicology, 102, 419–425.Google Scholar
  155. 155.
    Hei, T. K., Liu, S. X., & Waldren, C. (1998). Mutagenicity of arsenic in mammalian cells: Role of reactive oxygen species. Proceedings of the National Academy of Sciences of the United States of America, 5, 8103–8107.Google Scholar
  156. 156.
    Szeto, H. H. (2006). Cell permeable, mitochondrial-target, peptide antioxidants. American Association of Pharmaceutical Scientists Journal, 8, 277–278.Google Scholar
  157. 157.
    Dillard, C. J., & German, J. B. (2000). Phytochemicals: Nutraceuticals and human health. Journal of the Science of Food and Agriculture, 80, 1744–1756.Google Scholar
  158. 158.
    Gu, J., Gui, Y., Chen, L., Yuan, G., Lu, H., & Xu, X. (2013). Use of natural products as chemical library for drug discovery and network pharmacology. PLoS ONE, 8, e62839.Google Scholar
  159. 159.
    Nampoothiri, S. V., Binilraj, S. S., Prathapan, A., Abhilash, P. A., Arumughan, C., & Sundaresan, A. (2011). In vitro antioxidant activities of the methanol extract and its different solvent fractions obtained from the fruit pericarp of Terminalia bellerica. Natural Product Research, 25, 277–287.Google Scholar
  160. 160.
    Prathapan, A., Vineetha, V. P., Abhilash, P. A., & Raghu, K. G. (2013). Boerhaavia diffusa L. attenuates angiotensin II-induced hypertrophy in H9c2 cardiac myoblast cells via modulating oxidative stress and down-regulating NF-κB and transforming growth factor β1. British Journal of Nutrition, 110, 1201–1210.Google Scholar
  161. 161.
    Prathapan, A., Vineetha, V. P., & Raghu, K. G. (2014). Protective effect of Boerhaavia diffusa L. against mitochondrial dysfunction in angiotensin II induced hypertrophy in H9c2 cardiomyoblast cells. PLoS ONE, 9(4), e96220.Google Scholar
  162. 162.
    Vineetha, V. P., Prathapan, A., Soumya, R. S., & Raghu, K. G. (2013). Arsenic trioxide toxicity in H9c2 myoblasts—damage to cell organelles and possible amelioration with Boerhaavia diffusa. Cardiovascular Toxicology, 13, 123–137.Google Scholar
  163. 163.
    Bouayed, J., & Bohn, T. (2010). Exogenous antioxidants-double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxidative Medicine and Cellular Longevity, 3, 228–237.Google Scholar
  164. 164.
    Diplock, A. T., Charleux, J. L., Crozier-Willi, G., Kok, F. J., Rice-Evans, C., Roberfroid, M., Stahl, W., & Viña-Ribes, J. (1998). Functional food science and defence against reactive oxygen species. British Journal of Nutrition, 80, S77–S112.Google Scholar
  165. 165.
    Howard, B. V., & Kritchevsky, D. (1997). Phytochemicals and cardiovascular disease. A statement for healthcare professionals from the American Heart Association. Circulation, 95, 2591–2593.Google Scholar
  166. 166.
    Hu, F. B. (2003). Plant-based foods and prevention of cardiovascular diseases: An overview. American Journal of Clinical Nutrition, 78, 544S–551S.Google Scholar
  167. 167.
    Reddy, V. B. M., Sasikala, P., Karthik, A., Sudheer, S. D., & Murthy, L. N. (2012). Protective role of curcumin against arsenic trioxide toxicity during gestation and lactational periods. Global Veterinaria, 9, 270–276.Google Scholar
  168. 168.
    Zhao, X.-Y., Li, G.-Y., Liu, Y., Chai, L.-M., Chen, J.-X., Zhang, Y., Du, Z.-M., Lu, Y.-J., & Yang, B.-F. (2008). Resveratrol protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo. British Journal of Pharmacology, 154, 105–113.Google Scholar
  169. 169.
    Kumazaki, M., Ando, H., Kakei, M., Ushijima, K., Taniguchi, Y., Yoshida, M., Yamato, S., Washino, S., Koshimizu, T. A., & Fujimura, A. (2013). α-Lipoic acid protects against arsenic trioxide-induced acute QT prolongation in anesthetized guinea pigs. European Journal of Pharmacology, 705, 1–10.Google Scholar
  170. 170.
    Zhang, J.-Y., Wang, M., Wang, R.-Y., Sun, X., Du, Y.-Y., Ye, J.-X., Sun, G.-B., & Sun, X.-B. (2018). Salvianolic acid A ameliorates arsenic trioxide-induced cardiotoxicity through decreasing cardiac mitochondrial injury and promotes its anticancer activity. Frontiers in Pharmacology, 9, 487.Google Scholar
  171. 171.
    Sinha, M., Manna, P., & Sil, P. C. (2008). Arjunolic acid attenuates arsenic-induced nephrotoxicity. Pathophysiology, 15, 147–156.Google Scholar
  172. 172.
    Bors, W., Heller, W., Michel, C., & Saran, M. (1990). Flavonoids as antioxidants: Determination of radical-scavenging efficiencies. Methods in Enzymology, 186, 343–355.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Processing TechnologyKerala University of Fisheries and Ocean Studies (KUFOS)KochiIndia
  2. 2.Agroprocessing and Natural Products DivisionNational Institute for Interdisciplinary Science and Technology (CSIR - NIIST)ThiruvananthapuramIndia

Personalised recommendations