Abstract
This study was designed to indicate the cardiotoxicity due to 99mTc-MIBI injection in myocardial perfusion imaging in wistar Rats. In addition, protective effect of hesperidin/diosmin compound (HDC) against the cardiotoxicity was evaluated. Twenty five male rats were randomly divided into five groups. The rats in Group 1 (control) only received PBS. For Group 2 (HDC only) the rats treated with only HDC. The rats in Group 3 (radiation) received PBS before injection and exposure to 1 mCi 99mTc-MIBI. The rats in Group 4 (HDC + radiation) treated with HDC before exposure. For Group 5 (radiation + HDC) the rats were exposed and thereafter administered HDC. The Animals of this study were orally administered 100 mg/kg/day of the HDC for 7 days. Then, the rats were sacrificed and afterwards their heart tissues were carefully extracted for biochemical and histopathological evaluations. According to our results in the radiation group, the rate of rupture of cardiomyocyte fibers was higher than other groups, and in some fibers, the presence of lymphocytes was observed. Relative improvement was observed in radiation + HDC group compared to the radiation group and also a small number of cardiomyocyte fibers were torn and in some fibers, the presence of lymphocytes was observed, which was less than the model group. Collagen deposition significantly increased in radiation group compared to control group (P < 0.05). It can be seen that the percentage of collagen deposition decreased substantially in the group treated with HDC before or after radiation compared to radiation group (P < 0.05). The MDA activities significantly reduced (P < 0.05) in both (HDC + radiation) and (radiation + HDC) groups. SOD activity significantly increased in both (radiation + HDC) and (HDC + radiation) groups compared to that of radiation group (P < 0.05). It could be concluded that the HDC is safe and promising useful therapeutic agent in radiation induced cardiotoxicity for patients undergoing nuclear medicine procedures.
Graphical Abstract
Similar content being viewed by others
Data Availability
Available on request.
References
Yusuf, S. W., Venkatesulu, B. P., Mahadevan, L. S., & Krishnan, S. (2017). Radiation-induced cardiovascular disease: A clinical perspective. Frontiers in Cardiovascular Medicine, 4, 66. https://doi.org/10.3389/fcvm.2017.00066
Chen, J., Einstein, A. J., Fazel, R., Krumholz, H. M., Wang, Y., Ross, J. S., Ting, H. H., Shah, N. D., Nasir, K., & Nallamothu, B. K. (2010). Cumulative exposure to ionizing radiation from diagnostic and therapeutic cardiac imaging procedures: A population-based analysis. Journal of the American College of Cardiology, 56(9), 702–711. https://doi.org/10.1016/j.jacc.2010.05.014
Darby, S. C., Cutter, D. J., Boerma, M., Constine, L. S., Fajardo, L. F., Kodama, K., Mabuchi, K., Marks, L. B., Mettler, F. A., & Pierce, L. J. (2010). Radiation-related heart disease: Current knowledge and future prospects. International Journal of Radiation Oncology Biology, 76(3), 656–665. https://doi.org/10.1016/j.ijrobp.2009.09.064
Group EBCTC. (2005). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials. The Lancet, 366(9503), 2087–2106. https://doi.org/10.1016/S0140-6736(05)67887-7
Boice, J. D., Jr. (2007). An affair of the heart. Journal of the National Cancer Institute., 99(3), 186–187. https://doi.org/10.1093/jnci/djk058
Shimizu, Y., Kodama, K., Nishi, N., Kasagi, F., Suyama, A., Soda, M., Grant, E. J., Sugiyama, H., Sakata, R., & Moriwaki, H. (2010). Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950–2003. BMJ. https://doi.org/10.1136/bmj.b5349
Shimizu, Y., Kato, H., Schull, W. J., & Hoel, D. G. (1992). Studies of the mortality of A-bomb survivors. 9. Mortality, 1950–1985: Part 3. Noncancer mortality based on the revised doses (DS86). Radiation Research, 130(2), 249–266.
Wang, H., Wei, J., Zheng, Q., Meng, L., Xin, Y., Yin, X., & Jiang, X. (2019). Radiation-induced heart disease: A review of classification, mechanism and prevention. International Journal of Biological Sciences, 15(10), 2128. https://doi.org/10.7150/ijbs.35460
Salata, C., Ferreira-Machado, S. C., De Andrade, C. B. V., Mencalha, A. L., Mandarim-De-Lacerda, C. A., & de Almeida, C. E. (2014). Apoptosis induction of cardiomyocytes and subsequent fibrosis after irradiation and neoadjuvant chemotherapy. International Journal of Radiation Biology, 90(4), 284–290. https://doi.org/10.3109/09553002.2014.887869
Sridharan, V., Aykin-Burns, N., Tripathi, P., Krager, K. J., Sharma, S. K., Moros, E. G., Corry, P. M., Nowak, G., Hauer-Jensen, M., & Boerma, M. (2014). Radiation-induced alterations in mitochondria of the rat heart. Radiation Research, 181(3), 324–334. https://doi.org/10.1667/RR13452.1
Citrin, D., Cotrim, A. P., Hyodo, F., Baum, B. J., Krishna, M. C., & Mitchell, J. B. (2010). Radioprotectors and mitigators of radiation-induced normal tissue injury. The Oncologist, 15(4), 360. https://doi.org/10.1634/theoncologist.2009-S104
Hosseinimehr, S. J. (2007). Trends in the development of radioprotective agents. Drug Discovery Today, 12(19–20), 794–805. https://doi.org/10.1016/j.drudis.2007.07.017
Khezerloo, D., Mortezazadeh, T., Farhood, B., Sheikhzadeh, P., Seyfizadeh, N., & Pezhman, L. (2019). The effect of date palm seed extract as a new potential radioprotector in gamma-irradiated mice. Journal of Cancer Research and Therapeutics, 15(3), 517–521. https://doi.org/10.4103/jcrt.JCRT_1341_16
Zhang, Q.-Y., Wang, F.-X., Jia, K.-K., & Kong, L.-D. (2018). Natural product interventions for chemotherapy and radiotherapy-induced side effects. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2018.01253
Tejada, S., Pinya, S., Martorell, M., Capó, X., Tur, J. A., Pons, A., & Sureda, A. (2018). Potential anti-inflammatory effects of hesperidin from the genus citrus. Current Medicinal Chemistry, 25(37), 4929–4945. https://doi.org/10.2174/0929867324666170718104412
Kilic, K., Sakat, M. S., Yildirim, S., Kandemir, F. M., Gozeler, M. S., Dortbudak, M. B., & Kucukler, S. (2019). The amendatory effect of hesperidin and thymol in allergic rhinitis: An ovalbumin-induced rat model. European Archives of Oto-Rhino-Laryngology, 276(2), 407–415. https://doi.org/10.1007/s00405-018-5222-y
Cho, J. (2006). Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin. Archives of Pharmacal Research, 29(8), 699–706. https://doi.org/10.1007/BF02968255
Roohbakhsh, A., Parhiz, H., Soltani, F., Rezaee, R., & Iranshahi, M. (2015). Molecular mechanisms behind the biological effects of hesperidin and hesperetin for the prevention of cancer and cardiovascular diseases. Life Sciences, 124, 64–74. https://doi.org/10.1016/j.lfs.2014.12.030
Garg, A., Garg, S., Zaneveld, L., & Singla, A. (2001). Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytotherapy Research, 15(8), 655–669. https://doi.org/10.1002/ptr.1074
Rezaeyan, A., Haddadi, G. H., Hosseinzadeh, M., Moradi, M., & Najafi, M. (2016). Radioprotective effects of hesperidin on oxidative damages and histopathological changes induced by X-irradiation in rats heart tissue. Journal of Medical Physics/Association of Medical Physicists of India, 41(3), 182. https://doi.org/10.4103/0971-6203.189482
Srinivasan, S., & Pari, L. (2012). Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Chemico-Biological Interactions, 195(1), 43–51. https://doi.org/10.1016/j.cbi.2011.10.003
Kastrup, J., Petersen, P., Dejgård, A., Angelo, H. R., & Hilsted, J. (1987). Intravenous lidocaine infusion—a new treatment of chronic painful diabetic neuropathy? Pain, 28(1), 69–75. https://doi.org/10.1016/0304-3959(87)91061-X
Tanrikulu, Y., Şahin, M., Kismet, K., Kilicoglu, S. S., Devrim, E., Tanrikulu, C. S., Erdemli, E., Erel, S., Bayraktar, K., & Akkus, M. A. (2013). The protective effect of diosmin on hepatic ischemia reperfusion injury: an experimental study. Bosnian Journal of Basic Medical Sciences, 13(4), 218. https://doi.org/10.17305/bjbms.2013.2305
Imam, F., Al-Harbi, N. O., Al-Harbi, M. M., Ansari, M. A., Zoheir, K. M., Iqbal, M., Anwer, M. K., Al Hoshani, A. R., Attia, S. M., & Ahmad, S. F. (2015). Diosmin downregulates the expression of T cell receptors, pro-inflammatory cytokines and NF-κB activation against LPS-induced acute lung injury in mice. Pharmacological Research, 102, 1–11. https://doi.org/10.1016/j.phrs.2015.09.001
Mahgoub, S., Sallam, A. O., Sarhan, H. K., Ammar, A. A., & Soror, S. H. (2020). Role of Diosmin in protection against the oxidative stress induced damage by gamma-radiation in Wistar albino rats. Regulatory Toxicology and Pharmacology, 113, 104622. https://doi.org/10.1016/j.yrtph.2020.104622
Sezer, A., Usta, U., Kocak, Z., & Yagci, M. A. (2011). The effect of a flavonoid fractions diosmin+ hesperidin on radiation-induced acute proctitis in a rat model. Journal of Cancer Research and Therapeutics, 7(2), 152. https://doi.org/10.4103/0973-1482.8292
Abdel-Rafei, M., Amin, M., & Hasan, H. (2017). Novel effect of Daflon and low-dose γ-radiation in modulation of thioacetamide-induced hepatic encephalopathy in male albino rats. Human & Experimental Toxicology, 36(1), 62–81. https://doi.org/10.1177/0960327116637657
Dreyfuss, A. D., Goia, D., Shoniyozov, K., Shewale, S. V., Velalopoulou, A., Mazzoni, S., Avgousti, H., Metzler, S. D., Bravo, P. E., & Feigenberg, S. J. (2021). A novel mouse model of radiation-induced cardiac injury reveals biological and radiological biomarkers of cardiac dysfunction with potential clinical relevance. Clinical Cancer Research, 27(8), 2266–2276. https://doi.org/10.1158/1078-0432.CCR-20-3882
Cicone, F., Viertl, D., Quintela Pousa, A. M., Denoël, T., Gnesin, S., Scopinaro, F., Vozenin, M.-C., & Prior, J. O. (2017). Cardiac radionuclide imaging in rodents: A review of methods, results, and factors at play. Frontiers in Medicine, 4, 35. https://doi.org/10.3389/fmed.2017.00035
Fooladi, M., Cheki, M., Shirazi, A., Sheikhzadeh, P., Amirrashedi, M., Ghahramani, F. and Khoobi, M. (2021). Histopathological evaluation of protective effect of telmisartan against radiation-induced bone marrow injury. Journal of Biomedical Physics and Engineering. Retrieved from https://jbpe.sums.ac.ir/article_47577.html
Leary, S., Underwood, W., Anthony, R., Cartner, S., Corey, D., Grandin, T., Greenacre, C., Gwaltney-Brant, S., McCrackin, M. A., Meyer, R., Miller, D., Shearer, J., & Yanong, R. (2013). AVMA guidelines for the euthanasia of animals: 2013 edition. American Veterinary Medical Association.
Mathers, C. D., & Loncar, D. (2006). Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine, 3(11), e442. https://doi.org/10.1371/journal.pmed.0030442
Hosseinimehr, S. J. (2009). Potential utility of radioprotective agents in the practice of nuclear medicine. Cancer Biotherapy and Radiopharmaceuticals, 24(6), 723–731. https://doi.org/10.1089/cbr.2009.0635
Taibi, N., Aka, P., Kirsch-Volders, M., Bourgeois, P., Frühling, J., & Szpireer, C. (2006). Radiobiological effect of 99mTechnetium-MIBI in human peripheral blood lymphocytes: Ex vivo study using micronucleus/FISH assay. Cancer Letters, 233(1), 68–78. https://doi.org/10.1016/j.canlet.2005.02.032
Merz, T., Tatum, J., & Hirsch, J. (1986). Technetium-99m-labeled lymphocytes: A radiotoxicity study. Journal of Nuclear Medicine, 27(1), 105–110.
Yahyapour, R., Amini, P., Rezapoor, S., Rezaeyan, A., Farhood, B., Cheki, M., Fallah, H., & Najafi, M. (2018). Targeting of inflammation for radiation protection and mitigation. Current Molecular Pharmacology, 11(3), 203–210. https://doi.org/10.2174/1874467210666171108165641
Hosseinimehr, S., & Nemati, A. (2006). Radioprotective effects of hesperidin against gamma irradiation in mouse bone marrow cells. The British Journal of Radiology, 79(941), 415–418. https://doi.org/10.1259/bjr/40692384
Hosseinimehr, S. J., Ahmadi, A., Beiki, D., Habibi, E., & Mahmoudzadeh, A. (2009). Protective effects of hesperidin against genotoxicity induced by 99mTc-MIBI in human cultured lymphocyte cells. Nuclear Medicine and Biology, 36(7), 863–867. https://doi.org/10.1016/j.nucmedbio.2009.06.002
Di Meo, S., & Venditti, P. (2020). Evolution of the knowledge of free radicals and other oxidants. Oxidative Medicine and Cellular Longevity. https://doi.org/10.1155/2020/9829176
Pradeep, K., Park, S. H., & Ko, K. C. (2008). Hesperidin a flavanoglycone protects against γ-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats. European Journal of Pharmacology, 587(1–3), 273–280. https://doi.org/10.1016/j.ejphar.2008.03.052
Funding
The current study was supported under Grant Number 24420, Shahid Beheshti University of Medical Sciences.
Author information
Authors and Affiliations
Contributions
Both authors contributed equally to the design of the research, perform the experiment and data analysis and write the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Ethical Approval
The animals used for the experiments were conducted with approval from the ethical committee of Shahid Beheshti University of Medical Sciences (Approval Number: IR.SBMU.RETECH.REC.1399.520).
Consent to Participate
Not applicable.
Consent to Publish
Not applicable.
Additional information
Handling Editor: Lorraine Chalifour.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Koosha, F., Sheikhzadeh, P. Investigating Radioprotective Effect of Hesperidin/Diosmin Compound Against 99mTc-MIBI-Induced Cardiotoxicity: Animal Study. Cardiovasc Toxicol 22, 646–654 (2022). https://doi.org/10.1007/s12012-022-09744-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12012-022-09744-8