Evaluation of Metformin and Dehydrozingerone against fluorosis induced neurodevelopmental toxicity in preclinical models

Tejas Ahuja, Nitesh Kumar, Farmiza Begum, Rekha R. Shenoy

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


BACKGROUND: Inorganic fluoride is widely used in dental practices to treat problems like dental caries and also to prevent bone related issues. It has been reported that exposure to excess amounts of fluoride either through drinking water or other sources impairs vital functions of the body and can prove to be toxic specially for the central nervous system. Many studies have shown that sodium fluoride (NaF) crosses the blood brain barrier in early developmental stages and causes impairments related to learning and memory, anxiety, decreased locomotor ability and in some cases, depression like behaviour specially in children. This study aims at evaluating the neurotoxic effects of chronic exposure of NaF in developmental stages in albino Wistar rats using Pre-Natal in-vivo model. METHOD: In this model, adult male & female Wistar rats were procured & mated. Once the pregnancy was established in female rats, NaF (100 ppm) was fed via drinking water to the groups. For treatment groups, Metformin (200 mg/kg) & Dehydrozingerone (DHZ) (200 mg/kg) were administered along with NaF. Dosing was continued throughout the gestation and lactation period to the newly born pups via mother. After 21 days, pups were separated from mothers & direct dosing of both NaF & test doses to the rat pups was initiated until the end of experiment. At the end of dosing period, animals were taken for behavioural tests, biochemical estimation & histopathological studies. RESULT: NaF exposure significantly decreased learning, memory & locomotor ability was able to induce anxiety like behaviour. Levels of AchE & lipid peroxidation was found to be significantly elevated. GSH levels were significantly decreased in hippocampus & frontal cortex in disease group. Histopathology studies showed presence of degenerated neurons in hippocampus of disease group. It was also observed that treatment with Metformin & DHZ was able to ameliorate the cognitive impairment, improve condition of oxidative stress & decrease neuronal degeneration in rat pups (at p<0.05). CONCLUSION: This study shows that chronic exposure to NaF led to cognitive impairment & results showed that Metformin & DHZ has neuroprotective ability with special emphasis on antioxidant properties.

Original languageEnglish
Pages (from-to)e058668
JournalAlzheimer's & dementia : the journal of the Alzheimer's Association
Publication statusPublished - 01-12-2021

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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