A preclinical study on effect of betanin on sodium fluoride induced hepatorenal toxicity in Wistar rats

Darrel Castelino; Amrita Parida; Bharti Chogtu Magazine; Aqsa Fathima; Mohandas Rao K.G.

doi:10.1515/jcim-2024-0262

Article

A preclinical study on effect of betanin on sodium fluoride induced hepatorenal toxicity in Wistar rats

Darrel Castelino , Amrita Parida , Bharti Chogtu Magazine , Aqsa Fathima and Mohandas Rao K.G.

Published/Copyright: January 6, 2025

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From the journal Journal of Complementary and Integrative Medicine Volume 22 Issue 1

Abstract

Background

Excessive fluoride exposure leads to increased oxidative stress and lipid peroxidation, causing harmful effects on the metabolic organs in the human body. Betanin, a pigment obtained from beetroot, is seen to have powerful anti-inflammatory and antioxidant. The study was conducted to determine the role of betanin in fluoride induced hepato-renal toxicity in Wistar rats.

Methods

Twenty four rats were divided into four groups. Group Ⅰ (control) rats received 1 mL distilled water; group Ⅱ rats were administered 10 mg/kg of sodium fluoride (NaF); group Ⅲ received 10 mg/kg NaF and 50 mg/kg (low dose) betanin; group Ⅳ received 10 mg/kg NaF and 200 mg/kg (high dose) betanin. Animals were dosed orally for 90 days. Various markers of liver and kidney function as well as oxidative stress were measured. Liver and kidney samples were examined for histopathology.

Results

Animals in group Ⅱ had significantly increased levels of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, and blood urea nitrogen compared to the NaF + betanin treated animals (group Ⅲ & Ⅳ). Malondialdehyde, nitric oxide levels were significantly lower in rats treated with NaF + betanin (low and high dose). Histologically, in group II rats, signs of interstitial nephritis were seen in the kidneys while liver sections showed clear indication of features of fatty liver and inflammatory cell infiltration. Treatment with betanin alleviated the severity of histopathological changes induced by NaF.

Conclusions

Betanin significantly ameliorated NaF-induced oxidative stress and inflammation, therefore, has potential to be used as protective agent against fluoride induced hepato-renal toxicity.

Keywords: NaF; antioxidant; liver; kidney

Corresponding author: Dr. Amrita Parida, Associate Professor, Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India; and Co-coordinator, Center for Animal Research, Ethics and Training (CARET), Manipal Academy of Higher Education, Manipal, Karnataka, India, E-mail: amrita.parida@manipal.edu

Funding source: Manipal Academy of Higher Education

Award Identifier / Grant number: PG thesis grant number PGR660

Research ethics: The study protocol [IAEC/KMC/24/2023] was approved by the Institutional Animal Ethics Committee (IAEC), KMC, Manipal. Date of approval: 10th February 2023. The study was conducted as per the guidelines laid by Committee for Control and Supervision of Experiments on Animals (CCSEA), Government of India.
Informed consent: Not applicable.
Author contributions: Conceptualization, D.C.; A.P. and B.C.M.; methodology, D.C.; A.P. and A.F. software, D.C.; A.P.; validation, A.P. and B.C.M; formal analysis, D.C.; A.P; investigation, D.C.; M.R.K.G; and A.F.; resources, D.C.; M.R.K.G.; A.F.; data curation, D.C.; A.P.; M.R.K.G. and B.C.M; writing – original draft preparation, D.C.; writing – review and editing, A.P.; B.C.M., M.R.K.G; visualization, D.C. and A.P.; supervision, B.C.M, M.R.K.G. and A.P. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: This research was funded by postgraduate thesis grant (grant number PGR660) from Manipal Academy of Higher Education (MAHE).
Data availability: Not applicable.

References

1. Barbier, O, Arreola-Mendoza, L, Del Razo, LM. Molecular mechanisms of fluoride toxicity. Chem Biol Interact 2010;188:319–33. https://doi.org/10.1016/j.cbi.2010.07.011.Search in Google Scholar PubMed

2. Rao, Nagendra CR. Fluoride and environment–a review. In: Bunch MJ, Suresh VM, Kumaran TV, editors, Proceedings of the third international conference on environment and health. Department of Geography, University of Madras and Faculty of Environmental Studies, York University, Chennai; 2003:386–99 pp.Search in Google Scholar

3. Adelakun, SA, Ogunlade, B, Fidelis, OP, Adedotun, OA. Cyperus esculentus suppresses hepato-renal oxidative stress, inflammation, and caspase-3 activation following chronic exposure to sodium fluoride in rats’ model. Phytomedicine Plus 2022;2. https://doi.org/10.1016/j.phyplu.2021.100163.Search in Google Scholar

4. Azab, AE, Albasha, MO, Jbireal, JM, Adwas, AA. Sodium fluoride induces hepato-renal oxidative stress and pathophysiological changes in experimental animals. Open J Apoptosis 2018;7:1–23. https://doi.org/10.4236/ojapo.2018.71001.Search in Google Scholar

5. Lubojanski, A, Piesiak-Panczyszyn, D, Zakrzewski, W, Dobrzynski, W, Szymonowicz, M, Rybak, Z, et al.. The safety of fluoride compounds and their effect on the human body–a narrative review. Materials 2023;16:1242. https://doi.org/10.3390/ma16031242.Search in Google Scholar PubMed PubMed Central

6. Caglayan, C, Kandemir, FM, Darendelioğlu, E, Küçükler, S, Ayna, A. Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Sci 2021;281. https://doi.org/10.1016/j.lfs.2021.119730.Search in Google Scholar PubMed

7. Dhar, V, Bhatnagar, M. Physiology and toxicity of fluoride. Indian J Dent Res 2009;20:350–5. https://doi.org/10.4103/0970-9290.57379.Search in Google Scholar PubMed

8. Das, S, Dey, A, Maji, S, Sahoo, A, Barman, A, Santra, S, et al.. Attenuation of fluoride-induced hepatorenal oxidative stress by ferulic acid in vivo: an approach with in-silico analysis and interaction informatics of ferulic acid. J Trace Elem Med Biol 2023;77. https://doi.org/10.1016/j.jtemb.2023.127133.Search in Google Scholar PubMed

9. Zhan, XA, Wang, M, Xu, ZR, Li, JX, Li, JX. Toxic effects of fluoride on kidney function and histological structure in young pigs. Fluoride 2006;39:22–6.Search in Google Scholar

10. Cerklewski, FL. Fluoride bioavailability–nutritional and clinical aspects. Nutr Res (NY) 1997;17:907–29. https://doi.org/10.1016/s0271-5317(97)00057-2.Search in Google Scholar

11. Sharma, P, Verma, PK, Sood, S, Singh, M, Verma, D. Impact of chronic sodium fluoride toxicity on antioxidant capacity, biochemical parameters, and histomorphology in cardiac, hepatic, and renal tissues of wistar rats. Biol Trace Elem Res 2023;201:229–41. https://doi.org/10.1007/s12011-022-03113-w.Search in Google Scholar PubMed

12. Guo, XY, Sun, GF, Sun, YC. Oxidative stress from fluoride-induced hepatotoxicity in rats. Fluoride 2003;36:25–9.Search in Google Scholar

13. Yadu, B, Chandrakar, V, Keshavkant, S. Responses of plants to fluoride: an overview of oxidative stress and defense mechanisms. Fluoride 2016;49:293.Search in Google Scholar

14. Esatbeyoglu, T, Wagner, AE, Motafakkerazad, R, Nakajima, Y, Matsugo, S, Rimbach, G. Free radical scavenging and antioxidant activity of betanin: electron spin resonance spectroscopy studies and studies in cultured cells. Food Chem Toxicol 2014;73:119–26. https://doi.org/10.1016/j.fct.2014.08.007.Search in Google Scholar PubMed

15. Ahmadian, E, Khosroushahi, AY, Eghbal, MA, Eftekhari, A. Betanin reduces organophosphate induced cytotoxicity in primary hepatocyte via an anti-oxidative and mitochondrial dependent pathway. Pestic Biochem Physiol 2018;144:71–8. https://doi.org/10.1016/j.pestbp.2017.11.009.Search in Google Scholar PubMed

16. Gonçalves, LC, de Souza Trassi, MA, Lopes, NB, Dörr, FA, dos Santos, MT, Baader, WJ, et al.. A comparative study of the purification of betanin. Food Chem 2012;131:231–8. https://doi.org/10.1016/j.foodchem.2011.08.067.Search in Google Scholar

17. Silva, DV, Baiao, DD, Ferreira, VF, Paschoalin, VM. Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis. Crit Rev Food Sci Nutr 2021;62:539–54. https://doi.org/10.1080/10408398.2020.1822277.Search in Google Scholar PubMed

18. Esatbeyoglu, T, Wagner, AE, Schini‐Kerth, VB, Rimbach, G. Betanin–a food colorant with biological activity. Mol Nutr Food Res 2015;59:36–47. https://doi.org/10.1002/mnfr.201400484.Search in Google Scholar PubMed

19. Han, J, Ma, D, Zhang, M, Yang, X, Tan, D. Natural antioxidant betanin protects rats from paraquat-induced acute lung injury interstitial pneumonia. BioMed Res Int 2015;12:2015. https://doi.org/10.1155/2015/608174.Search in Google Scholar PubMed PubMed Central

20. Sadowska-Bartosz, I, Bartosz, G. Biological properties and applications of betalains. Molecules 2021;26:2520. https://doi.org/10.3390/molecules26092520.Search in Google Scholar PubMed PubMed Central

21. Mousavi, M, Abedimanesh, N, Mohammadnejad, K, Sharini, E, Nikkhah, M, Eskandari, MR, et al.. Betanin alleviates oxidative stress through the Nrf2 signaling pathway in the liver of STZ-induced diabetic rats. Mol Biol Rep 2022;49:9345–54. https://doi.org/10.1007/s11033-022-07781-8.Search in Google Scholar PubMed

22. Hadipour, E, Fereidoni, M, Tayarani-Najaran, Z. Betanin attenuates oxidative stress induced by 6-OHDA in PC12 cells via SAPK/JNK and PI3 K pathways. Neurochem Res 2020;45:395–403. https://doi.org/10.1007/s11064-019-02927-w.Search in Google Scholar PubMed

23. Stocks, J, Dormandy, TL. The autoxidation of human red cell lipids induced by hydrogen peroxide. Br J Haematol 1971;20:95–111. https://doi.org/10.1111/j.1365-2141.1971.tb00790.x.Search in Google Scholar PubMed

24. Eliman, G. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70–7. https://doi.org/10.1016/0003-9861(59)90090-6.Search in Google Scholar PubMed

25. Green, LC, Wagner, DA, Glogowski, J, Skipper, PL, Wishnok, JS, Tannenbaum, SR. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 1982;126:131–8. https://doi.org/10.1016/0003-2697(82)90118-x.Search in Google Scholar PubMed

26. Sellers, RS, Mortan, D, Michael, B, Roome, N, Johnson, JK, Yano, BL, et al.. Society of Toxicologic pathology position paper: organ weight recommendations for toxicology studies. Toxicol Pathol 2007;35:751–5. https://doi.org/10.1080/01926230701595300.Search in Google Scholar PubMed

27. Chanda, S, Parekh, J, Vaghasiya, Y, Dave, R, Baravalia, Y, Nair, R. Medicinal plants-from traditional use to toxicity assessment: a review. Int J Pharmaceut Sci Res 2015;6:2652.Search in Google Scholar

28. Albasher, G, Almeer, R, Alarifi, S, Alkhtani, S, Farhood, M, Al-Otibi, FO, et al. Nephroprotective role of Beta vulgaris L. root extract against chlorpyrifos-induced renal injury in rats. Evid base Compl Altern Med 2019;2019, https://doi.org/10.1155/2019/3595761.Search in Google Scholar PubMed PubMed Central

29. Sakr, S, Hamed, A, Atef, M. Betanin ameliorates fipronil-induced nephrotoxicity via activation of Nrf2-HO-1/NQO-1 pathway in albino rat model. Toxicol Res 2022;11:975–86. https://doi.org/10.1093/toxres/tfac076.Search in Google Scholar PubMed PubMed Central

30. Rose, MH, Sudha, P, Sudhakar, K. Effect of antioxidants and hepatoprotective activities of methanol extract of beet root (Beta vulgaris L.) against carbon tetrachloride induced hepatotoxicity in rat models. Int J Pharm Sci Res 2014;5:2546.Search in Google Scholar

31. Mahmood, SK, Askar, SJ. Study the hepatoprotective effects and oxidant-antioxidant status of beta vulgaris roots ethanolic extract in hepatotoxic rats induced by acetaminophen. Int J Health Sci 2022;6:1385–403. https://doi.org/10.53730/ijhs.v6ns5.8975.Search in Google Scholar

32. Albasher, G, Almeer, R, Al-Otibi, FO, Al-Kubaisi, N, Mahmoud, AM. Ameliorative effect of Beta vulgaris root extract on chlorpyrifos-induced oxidative stress, inflammation and liver injury in rats. Biomolecules 2019;9:261. https://doi.org/10.3390/biom9070261.Search in Google Scholar PubMed PubMed Central

33. Nirmal, NP, Medhe, S, Dahal, M, Koirala, P, Nirmal, S, Al-Asmari, F, et al.. Betalains protect various body organs through antioxidant and anti-inflammatory pathways. Food Sci Hum Wellness 2024;13:1109–17. https://doi.org/10.26599/fshw.2022.9250093.Search in Google Scholar

34. Tan, D, Wang, Y, Bai, B, Yang, X, Han, J. Betanin attenuates oxidative stress and inflammatory reaction in kidney of paraquat-treated rat. Food Chem Toxicol 2015;78:141–6, https://doi.org/10.1016/j.fct.2015.01.018.Search in Google Scholar PubMed

35. Yang, B, Cao, F, Zhao, H, Zhang, J, Jiang, B, Wu, Q. Betanin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress-myeloperoxidase/low-density lipoprotein in rat. Int J Clin Exp Pathol 2016;9:2777–86.Search in Google Scholar

36. Toth, S, Jonecova, Z, Maretta, M, Curgali, K, Kalpakidis, T, Pribula, M, et al.. The effect of Betanin parenteral pretreatment on Jejunal and pulmonary tissue histological architecture and inflammatory response after Jejunal ischemia-reperfusion injury. Exp Mol Pathol 2019;110. https://doi.org/10.1016/j.yexmp.2019.104292.Search in Google Scholar PubMed

37. Martinez, RM, Longhi-Balbinot, DT, Zarpelon, AC, Staurengo-Ferrari, L, Baracat, MM, Georgetti, SR, et al.. Anti-inflammatory activity of betalain-rich dye of Beta vulgaris: effect on edema, leukocyte recruitment, superoxide anion and cytokine production. Arch Pharm Res (Seoul) 2015;38:494–504. https://doi.org/10.1007/s12272-014-0473-7.Search in Google Scholar PubMed

Received: 2024-08-04

Accepted: 2024-11-18

Published Online: 2025-01-06

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Articles in the same Issue

https://doi.org/10.1515/jcim-2024-0262

Keywords for this article

NaF; antioxidant; liver; kidney