SpringerLink
Log in

Hesperidin Attenuates Oxidative Stress, Inflammation, Apoptosis, and Cardiac Dysfunction in Sodium Fluoride‐Induced Cardiotoxicity in Rats

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Excessive fluoride intake has been reported to cause toxicities to brain, thyroid, kidney, liver and testis tissues. Hesperidin (HSP) is an antioxidant that possesses anti-allergenic, anti-carcinogenic, anti-oxidant and anti-inflammatory activities. Presently, the studies focusing on the toxic effects of sodium fluoride (NaF) on heart tissue at biochemical and molecular level are limited. This study was designed to evaluate the ameliorative effects of HSP on toxicity of NaF on the heart of rats in vivo by observing the alterations in oxidative injury markers (MDA, SOD, CAT, GPX and GSH), pro-inflammatory markers (NF-κB, IL-1β, TNF-α), expressions of apoptotic genes (caspase-3, -6, -9, Bax, Bcl-2, p53, cytochrome c), levels of autophagic markers (Beclin 1, LC3A, LC3B), expression levels of PI3K/Akt/mTOR and cardiac markers. HSP treatment attenuated the NaF-induced heart tissue injury by increasing activities of SOD, CAT and GPx and levels of GSH, and suppressing lipid peroxidation. In addition, HSP reversed the changes in expression of apoptotic (caspase-3, -6, -9, Bax, Bcl-2, p53, cytochrome c), levels of autophagic and inflammatory parameters (Beclin 1, LC3A, LC3B, NF-κB, IL-1β, TNF-α), in the NaF-induced cardiotoxicity. HSP also modulated the gene expression levels of PI3K/Akt/mTOR signaling pathway and levels of cardiac markers (LDH, CK-MB). Overall, these findings reveal that HSP treatment can be used for the treatment of NaF-induced cardiotoxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Caron, S. (2020). Where does the fluorine come from? A review on the challenges associated with the synthesis of organofluorine compounds. Organic Process Research & Development, 24, 470–480. https://doi.org/10.1021/acs.oprd.0c00030

    Article  CAS  Google Scholar 

  2. James, P., Harding, M., Beecher, T., Browne, D., Cronin, M., Guiney, H., O’Mullane, D., & Whelton, H. (2020). Impact of reducing water fluoride on dental caries and fluorosis. Journal of Dental Research, 100, 507–514. https://doi.org/10.1177/0022034520978777

    Article  CAS  PubMed  Google Scholar 

  3. Solanki, Y. S., Agarwal, M., Maheshwari, K., Gupta, S., Shukla, P., & Gupta, A. B. (2021). Removal of fluoride from water by using a coagulant (inorganic polymeric coagulant). Environmental Science and Pollution Research, 28, 3897–3905. https://doi.org/10.1007/s11356-020-09579-2

    Article  CAS  PubMed  Google Scholar 

  4. Caglayan, C., Kandemir, F. M., Darendelioğlu, E., Küçükler, S., & Ayna, A. (2021). Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Sciences, 281, 119730. https://doi.org/10.1016/j.lfs.2021.119730

    Article  CAS  PubMed  Google Scholar 

  5. Pal, P., & Mukhopadhyay, P. K. (2021). Fluoride induced testicular toxicities in adult Wistar rats. Toxicology Mechanisms and Methods, 31, 383–392. https://doi.org/10.1080/15376516.2021.1891489

    Article  CAS  PubMed  Google Scholar 

  6. Oyagbemi, A. A., Omobowale, T. O., Ola-Davies, O. E., Asenuga, E. R., Ajibade, T. O., Adejumobi, O. A., Afolabi, J. M., Ogunpolu, B. S., Falayi, O. O., Saba, A. B., Adedapo, A. A., & Yakubu, M. A. (2018). Luteolin-mediated Kim-1/NF-kB/Nrf2 signaling pathways protects sodium fluoride-induced hypertension and cardiovascular complications. BioFactors, 44, 518–531. https://doi.org/10.1002/biof.1449

    Article  CAS  PubMed  Google Scholar 

  7. Atmaca, N., Atmaca, H. T., Kanici, A., & Anteplioglu, T. (2014). Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity in rats. Food and Chemical Toxicology, 70, 191–197. https://doi.org/10.1016/j.fct.2014.05.011

    Article  CAS  PubMed  Google Scholar 

  8. Akinrinde, A. S., Tijani, M., Awodele, O. A., & Oyagbemi, A. A. (2021). Fluoride-induced hepatotoxicity is prevented by L-Arginine supplementation via suppression of oxidative stress and stimulation of nitric oxide production in rats. Toxicology and Environmental Health Sciences, 13, 57–64. https://doi.org/10.1007/s13530-020-00070-6

    Article  Google Scholar 

  9. Özbolat, S. N., & Ayna, A. (2021). Chrysin suppresses HT-29 cell death induced by diclofenac through apoptosis and oxidative damage. Nutrition and Cancer, 73, 1419–1428. https://doi.org/10.1080/01635581.2020.1801775

    Article  CAS  PubMed  Google Scholar 

  10. Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Archives of toxicology, 94, 651–715. https://doi.org/10.1007/s00204-020-02689-3

    Article  CAS  PubMed  Google Scholar 

  11. Jucá, M. M., Cysne Filho, F. M. S., de Almeida, J. C., Mesquita, D. D. S., Barriga, J. R. D. M., Dias, K. C. F., Barbosa, T. M., Vasconcelos, L. C., Leal, L. K. A. M., Ribeiro, J. E., & Vasconcelos, S. M. M. (2020). Flavonoids: biological activities and therapeutic potential. Natural Product Research, 34, 692–705. https://doi.org/10.1080/14786419.2018.1493588

    Article  CAS  PubMed  Google Scholar 

  12. 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. https://doi.org/10.1007/s11356-020-11327-5

    Article  CAS  PubMed  Google Scholar 

  13. Caglayan, C., Demir, Y., Kucukler, S., Taslimi, P., Kandemir, F. M., & Gulçin, İ. (2019). The effects of hesperidin on sodium arsenite-induced different organ toxicity in rats on metabolic enzymes as antidiabetic and anticholinergics potentials: a biochemical approach. Journal of Food Biochemistry, 43, e12720. https://doi.org/10.1111/jfbc.12720

    Article  CAS  PubMed  Google Scholar 

  14. Shi, X., Niu, L., Zhao, L., Wang, B., **, Y., & Li, X. (2018). The antiallergic activity of flavonoids extracted from Citri Reticulatae Pericarpium. Journal of Food Processing and Preservation, 42, e13588. https://doi.org/10.1111/jfpp.13588

    Article  CAS  Google Scholar 

  15. Pandey, P., & Khan, F. (2021). A mechanistic review of the anticancer potential of hesperidin, a natural flavonoid from citrus fruits. Nutrition Research, 92, 21–31. https://doi.org/10.1016/j.nutres.2021.05.011

    Article  CAS  PubMed  Google Scholar 

  16. Küçükler, S., Çomaklı, S., Özdemir, S., Çağlayan, C., & Kandemir, F. M. (2021). Hesperidin protects against the chlorpyrifos-induced chronic hepato-renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy, and up-regulation of PARP-1/VEGF. Environmental Toxicology, 36, 1600–1617. https://doi.org/10.1002/tox.23156

    Article  CAS  PubMed  Google Scholar 

  17. Turk, E., Kandemir, F. M., Yildirim, S., Caglayan, C., Kucukler, S., & Kuzu, M. (2019). Protective effect of hesperidin on sodium arsenite-induced nephrotoxicity and hepatotoxicity in rats. Biological Trace Element Research, 189, 95–108. https://doi.org/10.1007/s12011-018-1443-6

    Article  CAS  PubMed  Google Scholar 

  18. Umarani, V., Muvvala, S., Ramesh, A., Lakshmi, B. V., & Sravanthi, N. (2015). Rutin potentially attenuates fluoride-induced oxidative stress-mediated cardiotoxicity, blood toxicity and dyslipidemia in rats. Toxicology Mechanism and Methods, 25, 143–149. https://doi.org/10.3109/15376516.2014.1003359

    Article  CAS  Google Scholar 

  19. Nabavi, S. F., Nabavi, S. M., Mirzaei, M., & Moghaddam, A. H. (2012). Protective effect of quercetin against sodium fluoride induced oxidative stress in rat’s heart. Food & Function, 3, 437–441. https://doi.org/10.1039/C2FO10264A

    Article  CAS  Google Scholar 

  20. Sun, Y., Oberley, L. W., & Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clinical Chemisty, 34, 497–500. https://doi.org/10.1093/clinchem/34.3.497

    Article  CAS  Google Scholar 

  21. Aebi, H. (1984). [13] Catalase in vitro. Methods in Enzymology, 105, 121–126. https://doi.org/10.1016/S0076-6879(84)05016-3

    Article  CAS  PubMed  Google Scholar 

  22. Lawrence, R. A., & Burk, R. F. (1976). Glutathione peroxidase activity in selenium-deficient rat liver. Biochemical and Biophysical Research Communications, 71, 952–958. https://doi.org/10.1016/0006-291X(76)90747-6

    Article  CAS  PubMed  Google Scholar 

  23. Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analitical Biochemistry, 25, 192–205. https://doi.org/10.1016/0003-2697(68)90092-4

    Article  CAS  Google Scholar 

  24. Placer, Z. A., Cushman, L. L., & Johnson, B. C. (1966). Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Analitical Biochemistry, 16, 359–364. https://doi.org/10.1016/0003-2697(66)90167-9

    Article  CAS  Google Scholar 

  25. Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193, 265–275. https://doi.org/10.1016/S0021-9258(19)52451-6

    Article  CAS  PubMed  Google Scholar 

  26. Kucukler, S., Caglayan, C., Darendelioğlu, E., & Kandemir, F. M. (2020). Morin attenuates acrylamide-induced testicular toxicity in rats by regulating the NF-κB, Bax/Bcl-2 and PI3K/Akt/mTOR signaling pathways. Life Sciences, 261, 118301. https://doi.org/10.1016/j.lfs.2020.118301

    Article  CAS  PubMed  Google Scholar 

  27. Tartik, M., Darendelioglu, E., Aykutoglu, G., & Baydas, G. (2016). Turkish propolis supresses MCF-7 cell death induced by homocysteine. Biomedicine and Pharmacotherapy, 82, 704–712. https://doi.org/10.1016/j.biopha.2016.06.013

    Article  CAS  PubMed  Google Scholar 

  28. Song, C., Shi, D., Chang, K., Li, X., Dong, Q., Ma, X., Wang, X., Guo, Z., Liu, Y., & Wang, J. (2021). Sodium fluoride activates the extrinsic apoptosis via regulating NOX4/ROS-mediated p53/DR5 signaling pathway in lung cells both in vitro and in vivo. Free Radical Biology and Medicine, 169, 137–148. https://doi.org/10.1016/j.freeradbiomed.2021.04.007

    Article  CAS  PubMed  Google Scholar 

  29. Brillo, V., Chieregato, L., Leanza, L., Muccioli, S., & Costa, R. (2021). Mitochondrial dynamics, ROS, and cell signaling: a blended overview. Life. https://doi.org/10.3390/life11040332

    Article  PubMed  PubMed Central  Google Scholar 

  30. Herb, M., & Schramm, M. (2021). Functions of ROS in macrophages and antimicrobial immunity. Antioxidants. https://doi.org/10.3390/antiox10020313

    Article  PubMed  PubMed Central  Google Scholar 

  31. Schieber, M., & Chandel, N. S. (2014). ROS function in redox signaling and oxidative stress. Current Biology, 24, R453–R462. https://doi.org/10.1016/j.cub.2014.03.034

    Article  CAS  PubMed  Google Scholar 

  32. Kucukler, S., Darendelioğlu, E., Caglayan, C., Ayna, A., Yıldırım, S., & Kandemir, F. M. (2020). Zingerone attenuates vancomycin-induced hepatotoxicity in rats through regulation of oxidative stress, inflammation and apoptosis. Life Sciences, 259, 118382. https://doi.org/10.1016/j.lfs.2020.118382

    Article  CAS  PubMed  Google Scholar 

  33. Caglayan, C., Kandemir, F. M., Yildirim, S., Kucukler, S., & Eser, G. (2019). Rutin protects mercuric chloride-induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats. Journal of Trace Element Medicine Biology, 54, 69–78. https://doi.org/10.1016/j.jtemb.2019.04.007

    Article  CAS  Google Scholar 

  34. Nkpaa, K. W., & Onyeso, G. I. (2018). Rutin attenuates neurobehavioral deficits, oxidative stress, neuro-inflammation and apoptosis in fluoride treated rats. Neuroscience Letters, 682, 92–99. https://doi.org/10.1016/j.neulet.2018.06.023

    Article  CAS  PubMed  Google Scholar 

  35. Bouasla, A., Barour, C., Bouasla, I., & Messarah, M. (2021). Beneficial effects of Punica granatum l. juice and gallic acid against kidney oxidative damage caused by sodium fluoride. Pharmaceutical Chemistry Journal, 55, 920–928. https://doi.org/10.1007/s11094-021-02516-8

    Article  CAS  Google Scholar 

  36. Yamaguti, P. M., Simões, A., Ganzerla, E., Souza, D. N., Nogueira, F. N., & Nicolau, J. (2013). Effects of single exposure of sodium fluoride on lipid peroxidation and antioxidant enzymes in salivary glands of rats. Oxidative Medicine and Cellular Longevity, 2013, 674593. https://doi.org/10.1155/2013/674593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Semis, H. S., Kandemir, F. M., Kaynar, O., Dogan, T., & Arikan, S. M. (2021). The protective effects of hesperidin against paclitaxel-induced peripheral neuropathy in rats. Life Sciences, 287, 120104. https://doi.org/10.1016/j.lfs.2021.120104

    Article  CAS  PubMed  Google Scholar 

  38. Volpe, C. M. O., Villar-Delfino, P. H., dos Anjos, P. M. F., & Nogueira-Machado, J. A. (2018). Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death & Disease, 9, 119. https://doi.org/10.1038/s41419-017-0135-z

    Article  CAS  Google Scholar 

  39. Yu, H., Lin, L., Zhang, Z., Zhang, H., & Hu, H. (2020). Targeting NF-κB pathway for the therapy of diseases: Mechanism and clinical study. Signal Transduction and Targeted Therapy, 5, 209. https://doi.org/10.1038/s41392-020-00312-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Chen, L., Kuang, P., Liu, H., Wei, Q., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2019). Sodium fluoride (NaF) induces inflammatory responses via activating MAPKs/NF-κB signaling pathway and reducing anti-inflammatory cytokine expression in the mouse liver. Biological Trace Element Research, 189, 157–171. https://doi.org/10.1007/s12011-018-1458-z

    Article  CAS  PubMed  Google Scholar 

  41. Holze, C., Michaudel, C., Mackowiak, C., Haas, D. A., Benda, C., Hubel, P., Pennemann, F. L., Schnepf, D., Wettmarshausen, J., Braun, M., Leung, D. W., Amarasinghe, G. K., Perocchi, F., Staeheli, P., Ryffel, B., & Pichlmair, A. (2018). Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway. Nature Immunology, 19, 130–140. https://doi.org/10.1038/s41590-017-0013-y

    Article  CAS  PubMed  Google Scholar 

  42. Gao, J., Tian, X., Yan, X., Wang, Y., Wei, J., Wang, X., Yan, X., & Song, G. (2021). Selenium exerts protective effects against fluoride-induced apoptosis and oxidative stress and altered the expression of Bcl-2/Caspase family. Biological Trace Element Research, 199, 682–692. https://doi.org/10.1007/s12011-020-02185-w

    Article  PubMed  Google Scholar 

  43. Wei, Q., Luo, Q., Liu, H., Chen, L., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2018). The mitochondrial pathway is involved in sodium fluoride (NaF)-induced renal apoptosis in mice. Toxicology Research, 7, 792–808. https://doi.org/10.1039/c8tx00130h

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rodius, S., de Klein, N., Jeanty, C., Sánchez-Iranzo, H., Crespo, I., Ibberson, M., Xenarios, I., Dittmar, G., Mercader, N., Niclou, S. P., & Azuaje, F. (2020). Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity. Scientific Reports, 10, 2896. https://doi.org/10.1038/s41598-020-59894-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Benzer, F., Kandemir, F. M., Ozkaraca, M., Kucukler, S., & Caglayan, C. (2018). Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats. Journal of Biochemical and Molecular Toxicology, 32, e22030. https://doi.org/10.1002/jbt.22030

    Article  CAS  Google Scholar 

  46. Yang, H., **ng, R., Liu, S., Yu, H., & Li, P. (2019). Analysis of the protective effects of γ-aminobutyric acid during fluoride-induced hypothyroidism in male Kunming mice. Pharmaceutical Biology, 57, 28–36. https://doi.org/10.1080/13880209.2018.1563621

    Article  CAS  Google Scholar 

  47. Hoxhaj, G., & Manning, B. D. (2020). The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nature Reviews Cancer, 20, 74–88. https://doi.org/10.1038/s41568-019-0216-7

    Article  CAS  PubMed  Google Scholar 

  48. Korkmaz, R., Yüksek, V., & Dede, S. (2021). The effects of sodium fluoride (NaF) treatment on the PI3K/Akt signal pathway in NRK-52E cells. Biological Trace Element Research. https://doi.org/10.1007/s12011-021-02927-4

    Article  PubMed  Google Scholar 

  49. Ma, L., Zhang, R., Li, D., Qiao, T., & Guo, X. (2021). Fluoride regulates chondrocyte proliferation and autophagy via PI3K/AKT/mTOR signaling pathway. Chemico-Biological Interactions, 349, 109659. https://doi.org/10.1016/j.cbi.2021.109659

    Article  CAS  PubMed  Google Scholar 

  50. Li, X., Hu, X., Wang, J., Xu, W., Yi, C., Ma, R., & Jiang, H. (2018). Inhibition of autophagy via activation of PI3K/Akt/mTOR pathway contributes to the protection of hesperidin against myocardial ischemia/reperfusion injury. International Journal of Molecular Medicine, 42, 1917–1924. https://doi.org/10.3892/ijmm.2018.3794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kandemir, F. M., Yıldırım, S., Kucukler, S., Caglayan, C., Darendelioğlu, E., & Dortbudak, M. B. (2020). Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food and Chemical Toxicology, 138, 111190. https://doi.org/10.1016/j.fct.2020.111190

    Article  CAS  PubMed  Google Scholar 

  52. He, C., & Levine, B. (2010). The beclin 1 interactome. Current Opinion in Cell Biology, 22, 140–149. https://doi.org/10.1016/j.ceb.2010.01.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kang, R., Zeh, H. J., Lotze, M. T., & Tang, D. (2011). The Beclin 1 network regulates autophagy and apoptosis. Cell Death & Differentiation, 18, 571–580. https://doi.org/10.1038/cdd.2010.191

    Article  CAS  Google Scholar 

  54. Koukourakis, M. I., Kalamida, D., Giatromanolaki, A., Zois, C. E., Sivridis, E., Pouliliou, S., Mitrakas, A., Gatter, K. C., & Harris, A. L. (2015). Autophagosome proteins LC3A, LC3B and LC3C have distinct subcellular distribution kinetics and expression in cancer cell lines. PLoS ONE, 10, e0137675. https://doi.org/10.1371/journal.pone.0137675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gur, C., Kandemir, O., & Kandemir, F. M. (2022). Investigation of the effects of hesperidin administration on abamectin-induced testicular toxicity in rats through oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, autophagy, and JAK2/STAT3 pathways. Environmental Toxicology, 37, 401–412. https://doi.org/10.1002/tox.23406

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Vocational School of Health Sevices, Final International University, Kazafani, Cyprus

    Behçet Varışlı

  2. Department of Molecular Biology and Genetics, Faculty of Science and Literature, Bingol University, 12000, Bingol, Turkey

    Ekrem Darendelioğlu

  3. Department of Biochemistry, Faculty of Veterinary Medicine, Bingol University, 12000, Bingol, Turkey

    Cuneyt Caglayan & Aydın Genç

  4. Department of Medical Biochemistry, Faculty of Medicine, Aksaray University, Aksaray, Turkey

    Fatih Mehmet Kandemir

  5. Department of Chemistry, Faculty of Science and Literature, Bingol University, 12000, Bingol, Turkey

    Adnan Ayna

  6. Technical Sciences Vocatinal School, Aksaray University, Aksaray, Turkey

    Özge Kandemir

Authors
  1. Behçet Varışlı
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ekrem Darendelioğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cuneyt Caglayan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatih Mehmet Kandemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adnan Ayna
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aydın Genç
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Özge Kandemir
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BV, CC and FMK designed the research. ED, ÖK and AG conducted experiments. ED, BV, FMK and AA analyzed data. BV, CC and AA wrote the manuscript. All authors read and approved the manuscript.

Corresponding authors

Correspondence to Cuneyt Caglayan or Fatih Mehmet Kandemir.

Ethics declarations

Conflict of interest

The authors have no conflict of interest. The authors report no declarations of interest.

Ethical approval

The experimental protocol was approved by the Animal Experiments Local Ethics Committee of the Bingol University (Protocol No. 2020-E.8227).

Consent to participate

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Varışlı, B., Darendelioğlu, E., Caglayan, C. et al. Hesperidin Attenuates Oxidative Stress, Inflammation, Apoptosis, and Cardiac Dysfunction in Sodium Fluoride‐Induced Cardiotoxicity in Rats. Cardiovasc Toxicol 22, 727–735 (2022). https://doi.org/10.1007/s12012-022-09751-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-022-09751-9

Keywords

Search

Navigation