Abstract

Background: Fluoride is an excitotoxin challenging the excitatory receptors and activate them continuously and also in proliferation of reactive oxygen and nitrogen species leading to neurodegeneration and its associated dysfunction. Chronic exposure to 20ppm sodium fluoride to pregnant rats is proven to be neurotoxic for the developing pups. Carica papaya is one of the medicinally important plants which exhibit anti-oxidative and anti-inflammatory responses.

Objective: The present study aimed to evaluate the neuroprotective properties of Carica papaya leaf extract (CPLE) against fluoride induced behavioural change and neurotransmitter loss.

Materials and methods: Timed pregnant Wistar rats (n=24) were chosen for the experiment and were divided into 4 groups (Group I: Control, Group II: 20 ppm Fluoride treated, Group III: 20 ppm Fluoride-50 mg CPLE, Group IV: 20 ppm Fluoride-100mg CPLE). The fluoride exposed groups received 20 ppm sodium fluoride (NaF) and two different concentrations of extract (50 and 100 mg/mL) through water for 52 days. The postnatal rat brains were collected after sacrificing them at regular time intervals (day 1, 7, 14, 21 and 30) and used to analyze the neurotransmitters alterations in cerebral cortex and hippocampus region of the brains.

Results: Our results suggest that chronic exposure of NaF to pregnant rats and pups during embryonic and postnatal stages had detrimental effects on the brain. The concentration of fluoride increased in brain tissue and serum with respect to treatment duration in fluoride groups (groups 2, 3 and 4). The levels of glutamate and aspartate increased whereas the levels of acetylcholine, epinephrine, nor-epinephrine, dopamine and serotonin diminished on NaF exposure. The other neurotoxic effects of fluoride are behavioural changes including learning, motor control and other behavioural deficits in postnatal rats.

Conclusion: The fluoride induced neurotransmitters and behavioural changes were ameliorated with CPLE administration, that were dose dependent i.e. 100 mg of CPLE showed better reversal efficiency than 50 mg extract.The present study reports the neuroprotective properties of Carica papaya leaf extract (CPLE) against fluoride-induced behavioral and neurotransmitter loss in developing rats. Day 1 pregnant Wistar rats (n = 24) were chosen as a model of study and were divided into four groups (Group I: control, Group II: 20 ppm fluoride treated, Group III: 20 ppm fluoride-50 mg CPLE, and Group IV: 20 ppm fluoride-100 mg CPLE). The fluoride-exposed groups received 20 ppm sodium fluoride (NaF) along with CPLE 50 or 100 mg/mL orally for 52 days. The brains of postnatal rats were collected at regular time intervals (day 1, 7, 14, 21, and 30) and used to analyze the neurotransmitters alterations in cerebral cortex and hippocampus region of the brain. The chronic exposure of NaF during embryonic and postnatal stages had detrimental effects on the brain. The levels of glutamate, aspartate, and epinephrine increased, whereas the levels of acetylcholine (Ach), norepinephrine, dopamine, and serotonin diminished on NaF exposure. Chronic fluoride exposure induced behavioral deficits (learning and motor control) in postnatal rats. The administration of CPLE extract has successfully ameliorated the fluoride-induced alterations in a dose-dependent manner, i.e. 100 mg of leaf extract showed better reversal efficiency than 50 mg extract.

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