Effect of naringin on sodium fluoride‑induced neurobehavioral deficits in Wistar rats

Swamy,Ravindra Shantakumar; Kumar,Nitesh; Shenoy,Smita; Kumar,Naveen; Rao,Vanishree

doi:10.3892/br.2024.1785

Effect of naringin on sodium fluoride‑induced neurobehavioral deficits in Wistar rats

Authors:
- Ravindra Shantakumar Swamy
- Nitesh Kumar
- Smita Shenoy
- Naveen Kumar
- Vanishree Rao
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Affiliations: Division of Anatomy, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research‑Hajipur, Hajipur, Bihar 844102, India, Department of Pharmacology, Kasturba Medical College‑Manipal, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India, Department of Anatomy, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates, Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
Published online on: April 29, 2024 https://doi.org/10.3892/br.2024.1785
Article Number: 97
Copyright: © Swamy et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

There is a lack of treatment for the detrimental effects of fluorosis. Sodium fluoride at a concentration of 10 ppm induces stress, depression and memory impairment in adult Wistar rats. Naringin, a flavanone glycoside isolated from citrus fruits such as lemons and oranges, possesses anti‑inflammatory, antioxidant and neuroprotective properties; therefore, it was used for treatment of fluoride induced toxicity in the present study. Adult Wistar rats were divided into eight groups (n=8). The normal control (NOR) group was provided with normal tap water. The sodium fluoride (FLU)10 group received water containing 10 ppm sodium fluoride for 60 days. The treatment groups (FLU10NAR100 and FLU10NAR50) received drinking water with 10 ppm sodium fluoride ad libitum along with Naringin 100 and 50 mg/kg body weight (bw) per oral gavage, respectively. The NAR100 and NAR50 groups received Naringin 100 and 50 mg/kg bw. The PRONAR100 and PRONAR50 groups received Naringin 100 and 50 mg/kg bw for the first 15 days and then subsequently received FLU10 ppm for 60 days (total of 75 days). All animals were subjected to behavioural tests consisting of the open field test (OFT), forced swim test (FST) and novel object recognition test (NORT). After euthanasia, the hippocampus and prefrontal cortex were stained with Cresyl violet. To measure the oxidative stress caused by fluoride and its effect on antioxidant levels, estimation of reduced glutathione (GSH) by Ellman's method, lipid peroxidation (LPO) measured in terms of the MDA:thiobarbituric acid reaction and catalase was performed. To evaluate the effect of fluoride on activity of acetylcholine, estimation of acetylcholinesterase (AChE) by Ellman's method was performed. In NORT and FST, significant changes (P<0.05) were present in the FLU10NAR100 and FLU10NAR50 groups compared with the FLU10 group, showing recovery from memory deficit and depression. The OFT results were insignificant. The LPO was reduced in all the other groups except the FLU10 group, with statistically significant changes. Catalase activity was significantly lower in FLU10 as compared with the NAR100, NAR50, PRONAR100 and PRONAR50 groups. GSH and AChE activities did not show significant changes as compared with the FLU10 group. The CA3 and prefrontal cortex viable and degenerated neuron count in the FLU10 group were insignificant compared with all other groups, except for the NAR100 and NAR50 groups. Thus, Naringin can be a useful drug to avoid the neurological effects of fluoride.

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1	Ali S, Fakhri Y, Golbini M, Thakur SK, Alinejad A, Parseh I, Shekhar S and Bhattacharya P: Concentration of fluoride in groundwater of India: A systematic review, meta-analysis and risk assessment. Groundw Sustain Dev. 9(100224)2019.
2	Ayoob S and Gupta AK: Fluoride in drinking water: A review on the status and stress effects. Crit Rev Environ Sci Technol. 36:433–487. 2006.
3	Amini M, Mueller K, Abbaspour KC, Rosenberg T, Afyuni M, Møller KN, Sarr M and Johnson CA: Statistical modeling of global geogenic fluoride contamination in groundwaters. Environ Sci Technol. 42:3662–3668. 2008.PubMed/NCBI View Article : Google Scholar
4	Chowdhury CR, Shahnawaz K, Kumari D, Chowdhury A, Bedi R, Lynch E, Harding S and Grootveld M: Spatial distribution mapping of drinking water fluoride levels in Karnataka, India: Fluoride-related health effects. Perspect Public Health. 136:353–360. 2016.PubMed/NCBI View Article : Google Scholar
5	Chowdhury A, Adak MK, Mukherjee A, Dhak P, Khatun J and Dhak D: A critical review on geochemical and geological aspects of fluoride belts, fluorosis and natural materials and other sources for alternatives to fluoride exposure. J Hydrol. 574:333–359. 2019.
6	DenBesten P and Li W: Chronic fluoride toxicity: Dental fluorosis. Monogr Oral Sci. 22:81–96. 2011.PubMed/NCBI View Article : Google Scholar
7	Shirani K, Yousefsani BS, Shirani M and Karimi G: Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review. Phytother Res. 34:1734–1744. 2020.PubMed/NCBI View Article : Google Scholar
8	Mani VM and Sadiq AMM: Naringin modulates the impairment of memory, anxiety, locomotor, and emotionality behaviors in rats exposed to deltamethrin; a possible mechanism association with oxidative stress, acetylcholinesterase and ATPase. Biomed Prev Nutr. 4:527–533. 2014.
9	Gindri Dos Santos B, Peres Klein C, Scortegagna Crestani M, Moura Maurmann R, Mateus Hözer R, Dos Santos Rodrigues K, Maciel August P and Matté C: Naringin supplementation during pregnancy induces sex and region-specific alterations in the offspring's brain redox status. Int J Environ Res Public Health. 18(4805)2021.PubMed/NCBI View Article : Google Scholar
10	Ahmed S, Khan H, Aschner M, Hasan MM and Hassan STS: Therapeutic potential of naringin in neurological disorders. Food Chem Toxicol. 132(110646)2019.PubMed/NCBI View Article : Google Scholar
11	Bharti S, Rani N, Krishnamurthy B and Arya DS: Preclinical evidence for the pharmacological actions of naringin: A review. Planta Med. 80:437–451. 2014.PubMed/NCBI View Article : Google Scholar
12	Jung UJ and Kim SR: Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain. Neural Regen Res. 9:1514–1517. 2014.PubMed/NCBI View Article : Google Scholar
13	Swamy RS, Kumar N, Shenoy S, Cheruku SP, Rao V, Kumar N, Kumar S and Ravichandiran V: Neuroprotective effect by naringin against fluorosis-induced neurodegeneration in adult Wistar rats. Neuroreport. 34:449–456. 2023.PubMed/NCBI View Article : Google Scholar
14	Bures J, Buresova O and Huston JP: Techniques and basic experiments for the study of brain and behavior. 2nd edition. Elsevier, Amsterdam, pp326, 1983.
15	El-Lethey H, Kamel M and Shaheed I: Neurobehavioral toxicity produced by sodium fluoride in drinking water of laboratory rats. J Am Sci. 6:54–63. 2010.
16	Antunes M and Biala G: The novel object recognition memory: Neurobiology, test procedure, and its modifications. Cogn Process. 13:93–110. 2012.PubMed/NCBI View Article : Google Scholar
17	Yankelevitch-Yahav R, Franko M, Huly A and Doron R: The forced swim test as a model of depressive-like behavior. J Vis Exp. 97(52587)2015.PubMed/NCBI View Article : Google Scholar
18	Zhu Y, Carvey PM and Ling Z: Age-related changes in glutathione and glutathione-related enzymes in rat brain. Brain Res. 1090:35–44. 2006.PubMed/NCBI View Article : Google Scholar
19	Aebi H: Catalase in vitro. Methods Enzymol. 105:121–126. 1984.PubMed/NCBI View Article : Google Scholar
20	Pohanka M, Hrabinova M, Kuca K and Simonato JP: Assessment of acetylcholinesterase activity using indoxylacetate and comparison with the standard Ellman's method. Int J Mol Sci. 12:2631–2640. 2011.PubMed/NCBI View Article : Google Scholar
21	Paxinos G and Watson C: The Rat Brain in Stereotaxic Coordinates. Academic Press, New York, NY, 1997.
22	Madhyastha S, Somayaji SN, Rao MS, Nalini K and Bairy KL: Hippocampal brain amines in methotrexate-induced learning and memory deficit. Can J Physiol Pharmacol. 80:1076–1084. 2002.PubMed/NCBI View Article : Google Scholar
23	Azami-Aghdash S, Ghojazadeh M, Pournaghi Azar F, Naghavi-Behzad M, Mahmoudi M and Jamali Z: Fluoride concentration of drinking waters and prevalence of fluorosis in iran: A systematic review. J Dent Res Dent Clin Dent Prospects. 7:1–7. 2013.PubMed/NCBI View Article : Google Scholar
24	Ranasinghe N, Kruger E and Tennant M: Spatial distribution of groundwater fluoride levels and population at risk for dental caries and dental fluorosis in Sri Lanka. Int Dent J. 69:295–302. 2019.PubMed/NCBI View Article : Google Scholar
25	Nagarajappa R, Pujara P, Sharda AJ, Asawa K, Tak M, Aapaliya P and Bhanushali N: Comparative assessment of intelligence quotient among children living in high and low fluoride areas of Kutch, India-a pilot study. Iran J Public Health. 42:813–818. 2013.PubMed/NCBI
26	Aravind A, Dhanya RS, Narayan A, Sam G, Adarsh VJ and Kiran M: Effect of fluoridated water on intelligence in 10-12-year-old school children. J Int Soc Prev Community Dent. 6 (Suppl 3):S237–S242. 2016.PubMed/NCBI View Article : Google Scholar
27	Rocha-Amador D, Elena Navarro M, Carrizales L, Morales R and Calderón J: Decreased intelligence in children and exposure to fluoride and arsenic in drinking water. Cad Saude Publica. 23 (Suppl 4):S579–S587. 2007.PubMed/NCBI View Article : Google Scholar
28	Malin AJ and Till C: Exposure to fluoridated water and attention deficit hyperactivity disorder prevalence among children and adolescents in the United States: An ecological association. Environ Health. 14(17)2015.PubMed/NCBI View Article : Google Scholar
29	Bartos M, Gumilar F, Gallegos CE, Bras C, Dominguez S, Mónaco N, Esandi MDC, Bouzat C, Cancela LM and Minetti A: Alterations in the memory of rat offspring exposed to low levels of fluoride during gestation and lactation: Involvement of the α7 nicotinic receptor and oxidative stress. Reprod Toxicol. 81:108–114. 2018.PubMed/NCBI View Article : Google Scholar
30	Manusha S, Sudhakar K and Reddy KP: Protective effects of allium sativum extract against sodium fluoride induced neurotoxicity. Int J Pharm Sci Res. 10:625–633. 2019.
31	Dong YT, Wei N, Qi XL, Liu XH, Chen D, Zeng XX and Guan ZZ: Attenuating effect of vitamin E on the deficit of learning and memory of rats with chronic fluorosis: The mechanism may involve muscarinic acetylcholine receptors. Fluoride. 50:354–364. 2017.
32	Kumar S, Shenoy S, Swamy RS, Ravichandiran V and Kumar N: Fluoride-induced mitochondrial dysfunction and approaches for its intervention. Biol Trace Elem Res. 202:835–849. 2024.PubMed/NCBI View Article : Google Scholar
33	Liu YJ, Gao Q, Wu CX and Guan ZZ: Alterations of nAChRs and ERK1/2 in the brains of rats with chronic fluorosis and their connections with the decreased capacity of learning and memory. Toxicol Lett. 192:324–329. 2010.PubMed/NCBI View Article : Google Scholar
34	Zhai JX, Guo ZY, Hu CL, Wang QN and Zhu QX: Studies on fluoride concentration and cholinesterase activity in rat hippocampus. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 21:102–104. 2003.PubMed/NCBI(In Chinese).
35	Zhao Q, Niu Q, Chen J, Xia T, Zhou G, Li P, Dong L, Xu C, Tian Z, Luo C, et al: Roles of mitochondrial fission inhibition in developmental fluoride neurotoxicity: Mechanisms of action in vitro and associations with cognition in rats and children. Arch Toxicol. 93:709–726. 2019.PubMed/NCBI View Article : Google Scholar
36	Ben-Azu B, Nwoke EE, Aderibigbe AO, Omogbiya IA, Ajayi AM, Olonode ET, Umukoro S and Iwalewa EO: Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice. Biomed Pharmacother. 109:536–546. 2019.PubMed/NCBI View Article : Google Scholar
37	Tran TH, Vo TTH, Vo TQN, Cao TCN and Tran TS: Synthesis and evaluation of the acetylcholinesterase inhibitory activities of some flavonoids derived from naringenin. ScientificWorldJournal. 2021(4817900)2021.PubMed/NCBI View Article : Google Scholar
38	Heo HJ, Kim MJ, Lee JM, Choi SJ, Cho HY, Hong B, Kim HK, Kim E and Shin DH: Naringenin from Citrus junos has an inhibitory effect on acetylcholinesterase and a mitigating effect on amnesia. Dement Geriatr Cogn Disord. 17:151–157. 2004.PubMed/NCBI View Article : Google Scholar
39	Massaad CA and Klann E: Reactive oxygen species in the regulation of synaptic plasticity and memory. Antioxid Redox Signal. 14:2013–2054. 2011.PubMed/NCBI View Article : Google Scholar
40	Sultana R, Perluigi M and Butterfield DA: Lipid peroxidation triggers neurodegeneration: A redox proteomics view into the Alzheimer disease brain. Free Radic Biol Med. 62:157–169. 2013.PubMed/NCBI View Article : Google Scholar
41	Kumar S, Chhabra V, Mehra M, K S, Kumar B H, Shenoy S, Swamy RS, Murti K, Pai KSR and Kumar N: The fluorosis conundrum: Bridging the gap between science and public health. Toxicol Mech Methods. 34:214–235. 2024.PubMed/NCBI View Article : Google Scholar
42	Ren C, Li HH, Zhang CY and Song XC: Effects of chronic fluorosis on the brain. Ecotoxicol Environ Saf. 244(114021)2022.PubMed/NCBI View Article : Google Scholar
43	Adedara IA, Abolaji AO, Idris UF, Olabiyi BF, Onibiyo EM, Ojuade TD and Farombi EO: Neuroprotective influence of taurine on fluoride-induced biochemical and behavioral deficits in rats. Chem Biol Interact. 261:1–10. 2017.PubMed/NCBI View Article : Google Scholar