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Betaine Protects Mice from Cardiotoxicity Triggered by Sodium Arsenite Through Antioxidative and Anti-inflammatory Pathways

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Abstract

NaAsO2 is known as a harmful pollutant all over the world, and many chronic heart diseases can be attributed to its prolonged exposure in NaAsO2-contaminated water. Therefore, considering the anti-inflammatory and antioxidant effects of betaine (BET), in this study, our team investigated the cardioprotective effects of this phytochemical agent on sodium arsenite (NaAsO2)-induced cardiotoxicity. Forty male mice were randomly divided into 4 groups: (I) Control; (II) BET (500 mg/kg); (III) NaAsO2 (50 ppm); and (IV) NaAsO2 + BET. NaAsO2 was given to the animals for 8 weeks, but BET was given in the last two weeks. After decapitation, inflammatory factors and biochemical parameters were measured, and Western blot analyses were performed. BET decrease the activity level of alanine aspartate aminotransferase, creatine kinase MB, thiobarbituric acid reactive substances level, inflammatory factors (tumor necrosis factor-α) content, and nuclear factor kappa B expression. Furthermore, BET increased cardiac total thiol and activity levels of catalase, superoxide dismutase, and glutathione peroxidase and nuclear factor erythroid-2 expression. Hence, the administration of BET ameliorated the deleterious effects stemming from the imbalance of oxidative and antioxidant pathways and histopathological alterations observed in NaAsO2-intoxicated mice, thereby attenuating oxidative stress-induced damage and inflammation.

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Data Availability

The datasets used and analyzed during the current study are available.

References

  1. Moon, K., Guallar, E., & Navas-Acien, A. (2012). Arsenic exposure and cardiovascular disease: An updated systematic review. Current Atherosclerosis Reports, 14, 542–555.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Jiang, X., & Yan, M. (2021). Surgical treatment for improved 1-year survival in patients with primary cardiac sarcoma. Anatolian Journal of Cardiology, 25, 796.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Zhu, Y., Huang, R., Wu, Z., Song, S., Cheng, L., & Zhu, R. (2021). Deep learning-based predictive identification of neural stem cell differentiation. Nature Communications, 12, 2614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Xiaolong, J., Jianhang, G., Jingyuan, T., Ke, M., & Yanqi, L. (2023). Research progress on degradation methods and product properties of plant polysaccharides. Journal of Light Industry, 38, 1.

    Google Scholar 

  5. Mumford, J. L., Wu, K., Xia, Y., Kwok, R., Yang, Z., Foster, J., & Sanders, W. E., Jr. (2007). Chronic arsenic exposure and cardiac repolarization abnormalities with QT interval prolongation in a population-based study. Environmental Health Perspectives, 115, 690–694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Alissa, E. M., & Ferns, G. A. (2011). Heavy metal poisoning and cardiovascular disease. Journal of Toxicology, 2011, 1.

    Article  Google Scholar 

  7. Mathews, V., Paul, M., Abhilash, M., Manju, A., Abhilash, S., & Nair, R. H. (2013). Myocardial toxicity of acute promyelocytic leukaemia drug-arsenic trioxide. European Review in Medicine and Pharmacological Science, 17, 34–38.

    Google Scholar 

  8. Zhou, L., Liu, Y., Sun, H., Li, H., Zhang, Z., & Hao, P. (2022). Usefulness of enzyme-free and enzyme-resistant detection of complement component 5 to evaluate acute myocardial infarction. Sensors and Actuators B: Chemical, 369, 132315.

    Article  CAS  Google Scholar 

  9. Fu, Q., Chen, R., Ding, Y., Xu, S., Huang, C., He, B., Jiang, T., Zeng, B., Bao, M., & Li, S. (2023). Sodium intake and the risk of various types of cardiovascular diseases: A Mendelian randomization study. Frontiers in Nutrition, 10, 1.

    Article  Google Scholar 

  10. Yang, W., Ding, N., Luo, R., Zhang, Q., Li, Z., Zhao, F., Zhang, S., Zhang, X., Zhou, T., & Wang, H. (2023). Exosomes from young healthy human plasma promote functional recovery from intracerebral hemorrhage via counteracting ferroptotic injury. Bioactive Materials, 27, 1–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yu, Y., Wang, L., Ni, S., Li, D., Liu, J., Chu, H. Y., Zhang, N., Sun, M., Li, N., & Ren, Q. (2022). Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation. Nature Communications, 13, 4241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Samanta, J., Mondal, A., Saha, S., Chakraborty, S., & Sengupta, A. (2020). Oleic acid protects from arsenic-induced cardiac hypertrophy via AMPK/FoxO/NFATc3 pathway. Cardiovascular Toxicology, 20, 261–280.

    Article  CAS  PubMed  Google Scholar 

  13. Klaassen, C. D., & Amdur, M. O. (2013). Casarett and Doull’s toxicology: The basic science of poisons. McGraw-Hill.

    Google Scholar 

  14. Moon, K. A., Guallar, E., Umans, J. G., Devereux, R. B., Best, L. G., Francesconi, K. A., Goessler, W., Pollak, J., Silbergeld, E. K., & Howard, B. V. (2013). Association between exposure to low to moderate arsenic levels and incident cardiovascular disease: A prospective cohort study. Annals of Internal Medicine, 159, 649–659.

    PubMed  PubMed Central  Google Scholar 

  15. Alamolhodaei, N. S., Shirani, K., & Karimi, G. (2015). Arsenic cardiotoxicity: An overview. Environmental Toxicology and Pharmacology, 40, 1005–1014.

    Article  CAS  PubMed  Google Scholar 

  16. Jomova, K., Jenisova, Z., Feszterova, M., Baros, S., Liska, J., Hudecova, D., Rhodes, C. J., & Valko, M. (2011). Arsenic: Toxicity, oxidative stress and human disease. Journal of Applied Toxicology, 31, 95–107.

    Article  CAS  PubMed  Google Scholar 

  17. Kuzu, M., Kandemir, F. M., Yıldırım, S., Çağlayan, C., & Küçükler, S. (2021). Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin. Environmental Science and Pollution Research, 28, 10818–10831.

    Article  CAS  PubMed  Google Scholar 

  18. De Zwart, F., Slow, S., Payne, R., Lever, M., George, P., Gerrard, J., & Chambers, S. (2003). Glycine betaine and glycine betaine analogues in common foods. Food Chemistry, 83, 197–204.

    Article  Google Scholar 

  19. Sakamoto, A., Nishimura, Y., Ono, H., & Sakura, N. (2002). Betaine and homocysteine concentrations in foods. Pediatrics International, 44, 409–413.

    Article  CAS  PubMed  Google Scholar 

  20. Craig, S. A. (2004). Betaine in human nutrition. The American Journal of Clinical Nutrition, 80, 539–549.

    Article  CAS  PubMed  Google Scholar 

  21. Alirezaei, M., Jelodar, G., Niknam, P., Ghayemi, Z., & Nazifi, S. (2011). Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum. Journal of Physiology and Biochemistry, 67, 605–612.

    Article  CAS  PubMed  Google Scholar 

  22. Al-Hafyan, S., Asoodeh, A., Baghshani, H., & Salari, L. E. (2023). Ameliorative potential of betaine against arsenite-induced hepatotoxicity and nephrotoxicity. Comparative Clinical Pathology, 1, 1–8.

    Google Scholar 

  23. Jung, Y. S., Kim, S. J., Kwon, D. Y., Ahn, C. W., Kim, Y. S., Choi, D. W., & Kim, Y. C. (2013). Alleviation of alcoholic liver injury by betaine involves an enhancement of antioxidant defense via regulation of sulfur amino acid metabolism. Food and Chemical Toxicology, 62, 292–298.

    Article  CAS  PubMed  Google Scholar 

  24. Day, C. R., & Kempson, S. A. (2016). Betaine chemistry, roles, and potential use in liver disease. Biochimica et Biophysica Acta (BBA)-General Subjects, 1860, 1098–1106.

    Article  CAS  PubMed  Google Scholar 

  25. Murillo-Fuentes, M. L., Artillo, R., Ubeda, N., Varela-Moreiras, G., Murillo, M. L., & Carreras, O. (2005). Hepatic S-adenosylmethionine after maternal alcohol exposure on offspring rats. Addiction Biology, 10, 139–144.

    Article  CAS  PubMed  Google Scholar 

  26. van der Veen, S., Hain, T., Wouters, J. A., Hossain, H., de Vos, W. M., Abee, T., Chakraborty, T., & Wells-Bennik, M. H. (2007). The heat-shock response of Listeria monocytogenes comprises genes involved in heat shock, cell division, cell wall synthesis, and the SOS response. Microbiology, 153, 3593–3607.

    Article  PubMed  Google Scholar 

  27. Burg, M. B. (1995). Molecular basis of osmotic regulation. American Journal of Physiology-Renal Physiology, 268, F983–F996.

    Article  CAS  Google Scholar 

  28. Qiu, H., Chen, X., Luo, Z., Zhao, L., Zhang, T., Yang, N., Long, X., Xie, H., Liu, J., & Xu, W. (2018). Inhibition of endogenous hydrogen sulfide production exacerbates the inflammatory response during urine-derived sepsis-induced kidney injury. Experimental and Therapeutic Medicine, 16, 2851–2858.

    PubMed  PubMed Central  Google Scholar 

  29. Bao, M.-H., Luo, H.-Q., Chen, L.-H., Tang, L., Ma, K.-F., Xiang, J., Dong, L.-P., Zeng, J., Li, G.-Y., & Li, J.-M. (2016). Impact of high fat diet on long non-coding RNAs and messenger RNAs expression in the aortas of ApoE(−/−) mice. Scientific Reports, 6, 34161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhou, Y., Sun, X., Yang, G., Ding, N., Pan, X., Zhong, A., Guo, T., Peng, Z., & Chai, X. (2023). Sex-specific differences in the association between steps per day and all-cause mortality among a cohort of adult patients from the United States with congestive heart failure. Heart & Lung, 62, 175–179.

    Article  Google Scholar 

  31. Tang, L., Wang, Y., Xiang, J., Yang, D., Zhang, Y., Xiang, Q., & Li, J. (2023). lncRNA and circRNA expression profiles in the hippocampus of Aβ 25–35-induced AD mice treated with tripterygium glycoside. Experimental and Therapeutic Medicine, 26, 1–14.

    Article  Google Scholar 

  32. Feng, S., Liu, W., Deng, S., Song, G., Zhou, J., Zheng, Z., & Song, Z. (2022). An atopic dermatitis-like mouse model by alternate epicutaneous application of dinitrofluorobenzene and an extract of dermatophagoides farinae. Frontiers in Medicine, 9, 843230.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sternbach, S., & McDonough, J. (2023). Betaine as a neuroprotective therapy in multiple sclerosis (Chapter 24). In C. R. Martin, V. B. Patel, & V. R. Preedy (Eds.), Treatments, nutraceuticals, supplements, and herbal medicine in neurological disorders (pp. 443–452). Academic Press.

    Chapter  Google Scholar 

  34. Ashtary-Larky, D., Bagheri, R., Ghanavati, M., Asbaghi, O., Tinsley, G. M., Mombaini, D., Kooti, W., Kashkooli, S., & Wong, A. (2022). Effects of betaine supplementation on cardiovascular markers: A systematic review and meta-analysis. Critical Reviews in Food Science and Nutrition, 62, 6516–6533.

    Article  CAS  PubMed  Google Scholar 

  35. Zhao, G., He, F., Wu, C., Li, P., Li, N., Deng, J., Zhu, G., Ren, W., & Peng, Y. (2018). Betaine in inflammation: Mechanistic aspects and applications. Frontiers in Immunology, 9, 1070.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ganesan, B., Buddhan, S., Anandan, R., Sivakumar, R., & AnbinEzhilan, R. (2010). Antioxidant defense of betaine against isoprenaline-induced myocardial infarction in rats. Molecular Biology Reports, 37, 1319–1327.

    Article  CAS  PubMed  Google Scholar 

  37. Wu, M.-M., Chiou, H.-Y., Hsueh, Y.-M., Hong, C.-T., Su, C.-L., Chang, S.-F., Huang, W.-L., Wang, H.-T., Wang, Y.-H., Hsieh, Y.-C., & Chen, C.-J. (2006). Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis. Toxicology and Applied Pharmacology, 216, 168–175.

    Article  CAS  PubMed  Google Scholar 

  38. Khodayar, M. J., Kalantari, H., Khorsandi, L., Rashno, M., & Zeidooni, L. (2018). Betaine protects mice against acetaminophen hepatotoxicity possibly via mitochondrial complex II and glutathione availability. Biomedicine & Pharmacotherapy, 103, 1436–1445.

    Article  CAS  Google Scholar 

  39. Dutta, S., Saha, S., Mahalanobish, S., Sadhukhan, P., & Sil, P. C. (2018). Melatonin attenuates arsenic induced nephropathy via the regulation of oxidative stress and inflammatory signaling cascades in mice. Food and Chemical Toxicology, 118, 303–316.

    Article  CAS  PubMed  Google Scholar 

  40. Ogihara, N., & Haley-Vicente, D. (2002). Protein target discovery and characterization-DS modeling and discovery studio streamline target discovery. Genetic Engineering News, 22, 77.

    Google Scholar 

  41. Tissue, E. (1959). Sulfhydryl groups. Archives in Biochemistry and Biophysics, 82, 70–77.

    Article  Google Scholar 

  42. Fossati, P., Prencipe, L., & Berti, G. (1980). Use of 3, 5-dichloro-2-hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clinical Chemistry, 26, 227–231.

    Article  CAS  PubMed  Google Scholar 

  43. Shangari, N., & O’Brien, P. J. (2006). Catalase activity assays. Current Protocols in Toxicology, 27, 1–16.

    Article  Google Scholar 

  44. Srivastava, S. (2020). Arsenic in drinking water and food. Springer.

    Book  Google Scholar 

  45. Yousuf, R., Verma, P. K., Sharma, P., Sood, S., Aït-Kaddour, A., & Bhat, Z. F. (2023). Ameliorative potential of quercetin and catechin against sodium arsenite and mancozeb-induced oxidative renal damage in Wistar rats. Journal of Trace Elements and Minerals, 1, 100079.

    Article  Google Scholar 

  46. Sevim, Ç., Doğan, E., & Comakli, S. (2020). Cardiovascular disease and toxic metals. Current Opinion in Toxicology, 19, 88–92.

    Article  Google Scholar 

  47. Bjørklund, G., Oliinyk, P., Lysiuk, R., Rahaman, M. S., Antonyak, H., Lozynska, I., Lenchyk, L., & Peana, M. (2020). Arsenic intoxication: General aspects and chelating agents. Archives of Toxicology, 94, 1879–1897.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hauptman, M., & Woolf, A. D. (2022). British anti-lewisite (dimercaprol) (Chapter 34). In A. D. Woolf (Ed.), History of modern clinical toxicology (pp. 243–254). Academic Press.

    Chapter  Google Scholar 

  49. Bhattacharya, S. (2017). Medicinal plants and natural products in amelioration of arsenic toxicity: A short review. Pharmaceutical Biology, 55, 349–354.

    Article  CAS  PubMed  Google Scholar 

  50. Yu, X., Wang, Z., Shu, Z., Li, Z., Ning, Y., Yun, K., Bai, H., Liu, R., & Liu, W. (2017). Effect and mechanism of Sorbus pohuashanensis (Hante) Hedl flavonoids protect against arsenic trioxide-induced cardiotoxicity. Biomedicine & Pharmacotherapy, 88, 1–10.

    Article  Google Scholar 

  51. Hosseinzadeh, A., Houshmand, G., Goudarzi, M., Sezavar, S. H., Mehrzadi, S., Mansouri, E., & Kalantar, M. (2019). Ameliorative effect of gallic acid on sodium arsenite-induced spleno-, cardio- and hemato-toxicity in rats. Life Sciences, 217, 91–100.

    Article  CAS  PubMed  Google Scholar 

  52. Manna, P., Sinha, M., & Sil, P. C. (2008). Arsenic-induced oxidative myocardial injury: Protective role of arjunolic acid. Archives of Toxicology, 82, 137–149.

    Article  CAS  PubMed  Google Scholar 

  53. Shen, S., Li, X.-F., Cullen, W. R., Weinfeld, M., & Le, X. C. (2013). Arsenic binding to proteins. Chemical Reviews, 113, 7769–7792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Shi, H., Shi, X., & Liu, K. J. (2004). Oxidative mechanism of arsenic toxicity and carcinogenesis. Molecular and Cellular Biochemistry, 255, 67–78.

    Article  CAS  PubMed  Google Scholar 

  55. Roth, R., & JH, L.J. (2019). Casarett & Doull’s toxicology: The basic science of poisons. McGraw-Hill Education.

    Google Scholar 

  56. Gamble, M. V., Liu, X., Ahsan, H., Pilsner, J. R., Ilievski, V., Slavkovich, V., Parvez, F., Levy, D., Factor-Litvak, P., & Graziano, J. H. (2005). Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environmental Health Perspectives, 113, 1683–1688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Catena, C., Colussi, G., Url-Michitsch, M., Nait, F., & Sechi, L. A. (2015). Subclinical carotid artery disease and plasma homocysteine levels in patients with hypertension. Journal of the American Society of Hypertension, 9, 167–175.

    Article  CAS  PubMed  Google Scholar 

  58. Ganguly, P., & Alam, S. F. (2015). Role of homocysteine in the development of cardiovascular disease. Nutrition Journal, 14, 1–10.

    Article  Google Scholar 

  59. Kolling, J., Scherer, E. B., Da Cunha, A. A., Da Cunha, M. J., & Wyse, A. T. (2011). Homocysteine induces oxidative–nitrative stress in heart of rats: Prevention by folic acid. Cardiovascular Toxicology, 11, 67–73.

    Article  CAS  PubMed  Google Scholar 

  60. Catena, C., Colussi, G., Nait, F., Capobianco, F., & Sechi, L. A. (2015). Elevated homocysteine levels are associated with the metabolic syndrome and cardiovascular events in hypertensive patients. American Journal of Hypertension, 28, 943–950.

    Article  CAS  PubMed  Google Scholar 

  61. Hoffmann, L., Brauers, G., Gehrmann, T., Häussinger, D., Mayatepek, E., Schliess, F., & Schwahn, B. C. (2013). Osmotic regulation of hepatic betaine metabolism. American Journal of Physiology-Gastrointestinal and Liver Physiology, 304, 835–846.

    Article  Google Scholar 

  62. Navik, U., Sheth, V. G., Kabeer, S. W., & Tikoo, K. (2019). Dietary supplementation of methyl donor l-methionine alters epigenetic modification in type 2 diabetes. Molecular Nutrition & Food Research, 63, 1801401.

    Article  CAS  Google Scholar 

  63. Go, E. K., Jung, K. J., Kim, J. M., Lim, H., Lim, H. K., Yu, B. P., & Chung, H. Y. (2007). Betaine modulates age-related NF-κB by thiol-enhancing action. Biological and Pharmaceutical Bulletin, 30, 2244–2249.

    Article  CAS  PubMed  Google Scholar 

  64. Hasanzadeh-Moghadam, M., Khadem-Ansari, M. H., Farjah, G. H., & Rasmi, Y. (2018). Hepatoprotective effects of betaine on liver damages followed by myocardial infarction. Veterinary Research Forum: An International Quarterly Journal, 9, 129–135.

    PubMed  Google Scholar 

  65. Ganesan, B., Buddhan, S., Jeyakumar, R., & Anandan, R. (2009). Protective effect of betaine on changes in the levels of membrane-bound ATPase activity and mineral status in experimentally induced myocardial infarction in Wistar rats. Biological Trace Element Research, 131, 278–290.

    Article  CAS  PubMed  Google Scholar 

  66. Barchowsky, A., Dudek, E. J., Treadwell, M. D., & Wetterhahn, K. E. (1996). Arsenic induces oxidant stress and NF-kB activation in cultured aortic endothelial cells. Free Radical Biology and Medicine, 21, 783–790.

    Article  CAS  PubMed  Google Scholar 

  67. Balakumar, P., & Kaur, J. (2009). Arsenic exposure and cardiovascular disorders: An overview. Cardiovascular Toxicology, 9, 169–176.

    Article  CAS  PubMed  Google Scholar 

  68. Patel, D., Yadav, P., Singh, S. K., Tanwar, S. S., Sehrawat, A., Khurana, A., Bhatti, J. S., & Navik, U. (2024). Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO− 1/NLRP3 and TGF-β expression. Journal of Biochemical and Molecular Toxicology, 38, e23559.

    Article  CAS  PubMed  Google Scholar 

  69. Jiang, Y.-P., Yang, J.-M., Ye, R.-J., Liu, N., Zhang, W.-J., Ma, L., Zheng, P., Niu, J.-G., Liu, P., & Yu, J.-Q. (2019). Protective effects of betaine on diabetic induced disruption of the male mice blood-testis barrier by regulating oxidative stress-mediated p38 MAPK pathways. Biomedicine & Pharmacotherapy, 120, 109474.

    Article  CAS  Google Scholar 

  70. Go, E. K., Jung, K. J., Kim, J. Y., Yu, B. P., & Chung, H. Y. (2005). Betaine suppresses proinflammatory signaling during aging: The involvement of nuclear factor-κB via nuclear factor-inducing kinase/IκB kinase and mitogen-activated protein kinases. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 60, 1252–1264.

    Article  PubMed  Google Scholar 

  71. Khodayar, M., Kalantari, H., Khorsandi, L., Rashno, M., & Zeidooni, L. (2020). Upregulation of Nrf2-related cytoprotective genes expression by acetaminophen-induced acute hepatotoxicity in mice and the protective role of betaine. Human & Experimental Toxicology, 39, 948–959.

    Article  CAS  Google Scholar 

  72. Urschel, K., & Cicha, I. (2015). TNF-α in the cardiovascular system: From physiology to therapy. International Journal of Interferon, Cytokine and Mediator Research, 7, 9–25.

    CAS  Google Scholar 

  73. Gutierrez, S. H., Kuri, M. R., & del Castillo, E. R. (2008). Cardiac role of the transcription factor NF-κB. Cardiovascular & Haematological Disorders-Drug Targets, 8, 153–160.

    Article  CAS  Google Scholar 

  74. Berthonneche, C., Sulpice, T., Boucher, F., Gouraud, L., De Leiris, J., O’connor, S., Herbert, J.-M., & Janiak, P. (2004). New insights into the pathological role of TNF-α in early cardiac dysfunction and subsequent heart failure after infarction in rats. American Journal of Physiology-Heart and Circulatory Physiology, 287, 340–350.

    Article  Google Scholar 

  75. Lau, A., Whitman, S. A., Jaramillo, M. C., & Zhang, D. D. (2013). Arsenic-mediated activation of the Nrf2-Keap1 antioxidant pathway. Journal of biochemical and molecular toxicology, 27, 99–105.

    Article  CAS  PubMed  Google Scholar 

  76. Zhang, Y., Wei, Z., Liu, W., Wang, J., He, X., Huang, H., Zhang, J., & Yang, Z. (2017). Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K/AKT pathway. Oncotarget, 8, 3773.

    Article  PubMed  Google Scholar 

  77. Nikravesh, M., Mahdavinia, M., Neisi, N., Khorsandi, L., & Khodayar, M. J. (2023). Citicoline ameliorates arsenic-induced hepatotoxicity and diabetes in mice by overexpression of VAMP2, PPAR-γ, As3MT, and SIRT3. Pesticide Biochemistry and Physiology, 192, 105391.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Parts of the graphical abstract were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.

Funding

This study was supported by a student grant from the Student Research Committee (Grant No: 00s86) of AJUMS.

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Data collection, investigation, data analysis, and writing original draft and editing were performed by S.S. Methodology, validation, and consultation were performed by M.S. Methodology and investigation were performed by R.A. Pathological analysis and consultation were performed by L.K. Conceptualization, validation, methodology, writing and editing, and supervision were performed by MJ.K. All authors reviewed and approved the manuscript.

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Correspondence to Mohammad Javad Khodayar.

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Shariati, S., Shirani, M., Azadnasab, R. et al. Betaine Protects Mice from Cardiotoxicity Triggered by Sodium Arsenite Through Antioxidative and Anti-inflammatory Pathways. Cardiovasc Toxicol 24, 539–549 (2024). https://doi.org/10.1007/s12012-024-09864-3

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