Effect of Ginkgo biloba extract on Histomorphometric changes of Hippocampus against Fluoride Toxicity in Wistar Rats

Jump To References Section


  • Department of Anatomy, Fathima Institute of Medical Sciences (FIMS), Dr. N.T.R. University of Health Sciences, Kadapa – 516003, Andhra Pradesh ,IN
  • Department of Anatomy, Viswabharathi Medical College and General Hospital, Dr. N.T.R. University of Health Sciences, Kurnool – 518463, Andhra Pradesh ,IN




Fluoride, Ginkgo biloba, Hippocampus, Histomorphometry, Neuron


Prolonged ingestion of fluoride leads to the pathogenesis known as fluorosis. Fluoride exposure leads to neuro degenerative changes such as reduction in the neuronal cell size and number. Exposure to fluoride showed neurodegenerative changes like shrunken neurons, increased in folding of the nuclear membrane, mitochondrial alterations, and dilated rough endoplasmic reticulum cisternae and clusters of vesicles near the Golgi bodies. Present study is to explore the histomorphometric changes of the hippocampus of fluoride induced brain and treated with Ginkgo biloba Extract (GBE). Thirty number (30) adult male Wistar rats were randomly separated into 5 Groups (n=6). Group1 (Control) supplemented with water, 2 to 5 Groups were supplemented with 100ppm of sodium fluoride for 30 days, while the Groups 3, 4, and 5 were Ginkgo biloba extract treated at 50mg/ kg, 100mg/kg and 200mg/kg body weight for 15 days, after sodium fluoride treatment, results showed that, 200mg/kg GBE provided effective and complete protection against fluoride toxicity. From the present study concluded that 50, 100 and 200 mg/kg GBE was significantly attenuated the fluoride induced toxicity in a dose depending manner. Present histomorphometrical study showed delayed neuronal death in the CA1 and CA3 regions of hippocampus of fluoride group that was significantly attenuated by GBE (50,100 and 200 mg/kg) in a dose dependant manner.


Download data is not yet available.



How to Cite

Raju, S., & Kanchanalatha, G. (2022). Effect of <i>Ginkgo biloba</i> extract on Histomorphometric changes of Hippocampus against Fluoride Toxicity in Wistar Rats. Toxicology International, 29(1), 125–131. https://doi.org/10.18311/ti/2022/v29i1/28484



Original Research
Received 2021-08-25
Accepted 2021-11-03
Published 2022-05-20



Dean HT, Elvove E. Studies on the minimal threshold of the dental sign of chronic endemic fluorosis (mottled enamel). Public Health Reports (1896-1970). 1935; 1719-1729. https://doi.org/10.2307/4581707.

Dhar V, Bhatnagar M. Physiology and toxicity of fluoride. Indian Journal of Dental Research. 2009; 20(3):350. https:// doi.org/10.4103/0970-9290.57379. PMid:19884722.

Spittle B. Psychopharmacology of fluoride: A review. International Clinical Psychopharmacology. 1994; 9(2):79- 82. https://doi.org/10.1097/00004850-199400920-00002. PMid:8056997.

Reddy PH. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular medicine. 2008; 10(4):291-315. https://doi.org/10.1007/s12017-008-8044-z. PMid:18566920 PMCid:PMC3235551.

Mullenix PJ, Denbesten PK, Schunior A, Kernan WJ. Neurotoxicity of sodium fluoride in rats. Neurotoxicology and Teratology. 1995; 17(2):169-177. https://doi. org/10.1016/0892-0362(94)00070-T. PMID: 7760776.

Varner JA, Jensen KF, Horvath W, Isaacson RL. Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water: Alterations in neuronal and cerebrovascular integrity. Brain Research. 1998; 784(1-2):284-298. https://doi.org/10.1016/S0006-8993(97)01336-X.

Ge Y, Ning H, Wang S, Wang J. Effects of high fluoride and low iodine on brain histopathology in offspring rats. Fluoride. 2005; 38(2):127-132.

Dubey AK, Shankar PR, Upadhyaya D, Deshpande VY. Ginkgo biloba--an appraisal. Kathmandu University Medical Journal (KUMJ). 2004 Jul 1; 2(3):225-229. PMID: 16400219.

Jetti R, Raghuveer CV, Mallikarjuna RC. Protective effect of ascorbic acid and Ginkgo biloba against learning and memory deficits caused by fluoride. Toxicology and Industrial Health. 2016; 32(1):183-187. https://doi. org/10.1177%2F0748233713498460. PMID: 24081631.

Blaylock RL. Excitotoxicity: A possible central mechanism in fluoride neurotoxicity. Fluoride. 2004 Nov 1; 37(4):301- 314.

Zhu W, Zhang J, Zhang Z. Effects of fluoride on synaptic membrane fluidity and PSD-95 expression level in rat hippocampus. Biological Trace Element Research. 2011; 139(2):197-203. https://doi.org/10.1007/s12011-010-8654- 9.

Bhatnagar M, Rao P, Jain S, Bhatnagar R. Neurotoxicity of fluoride: Neurodegeneration in hippocampus of female mice. PMID: 12622200.

Guan Z, Wang Y, Xiao K. Influence of experimental fluorosis on phospholipid content and fatty acid composition in rat brain. Zhonghua yi xue za zhi. 1997; 77(8):592-596. PMID: 9772465.

Shivarajashankara YM, Shivashankara AR, Bhat PG, Rao SM, Rao SH. Histological changes in the brain of young fluoride-intoxicated rats. Fluoride. 2002; 35(1):12-21. http://eprints.manipal.edu/id/eprint/2234.

Chen Y, Han F, Zhou Z, Zhang H, Jiao X, Zhang S, Huang M, Chang T, Dong Y. Research on the intellectual development of children in high fluoride areas. Fluoride. 2008; 41(2):120-124.

Zhang WR, Hayashi T, Kitagawa H, Sasaki C, Sakai K, Warita H, Wang JM, Shiro Y, Uchida M, Abe K. Protective effect of ginkgo extract on rat brain with transient middle cerebral artery occlusion. Neurological Research. 2000; 22(5):517-532. https://doi.org/10.1080/01616412.2000.117 40713. PMID: 10935227.

Reddy PY, Reddy KP, Kumar KP. Neurodegenerative changes in different regions of brain, spinal cord and sciatic nerve of rats treated with sodium fluoride. Journal of Medical and Allied Sciences. 2011 Jan 31; 1(1):30.

?ener G, Sehirli Ö, Tozan A, Velio?lu-Övunç A, Gedik N, Omurtag GZ. Ginkgo biloba extract protects against mercury (II)-induced oxidative tissue damage in rats. Food and Chemical Toxicology. 2007; 45(4):543-550. https://doi. org/10.1016/j.fct.2006.07.024. PMID: 17267089.

Tchantchou F, Lacor PN, Cao Z, Lao L, Hou Y, Cui C, Klein WL, Luo Y. Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. Journal of Alzheimer’s Disease. 2009; 18(4):787-798. https://doi.org/10.3233/JAD-2009- 1189. PMID: 19661619.

Yoo DY, Nam Y, Kim W, Yoo KY, Park J, Lee CH, Choi JH, Yoon YS, Kim DW, Won MH, Hwang IK. Effects of Ginkgo biloba extract on promotion of neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice. Journal of Veterinary Medical Science. 2011; 73(1):71-76. https://doi. org/10.1292/jvms.10-0294. PMID: 20814173.

Bastianetto S, Ramassamy C, Doré S, Christen Y, Poirier J, Quirion R. The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by ??amyloid. European Journal of Neuroscience. 2000; 12(6):1882-1890. https://doi.org/10.1046/j.1460- 9568.2000.00069.x. PMID: 10886329.

Chandrasekaran K, Mehrabian Z, Spinnewyn B, Drieu K, Fiskum G. Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia. Brainresearch. 2001; 20;922(2):282- 292. https://doi.org/10.1016/S0006-8993(01)03188-2.

Li W, Trovero F, Cordier J, Wang Y, Drieu K, Papadopoulos V. Prenatal exposure of rats to Ginkgo biloba extract (EGb 761) increases neuronal survival/growth and alters gene expression in the developing fetal hippocampus. Developmental Brain Research. 2003; 144(2):169-180. https://doi.org/10.1016/s0165-3806(03)00168-8. PMID: 12935914.