Neurotoxicity of fluoride in ethanol fed rats: Role of oxidative stress, mitochondrial dysfunction and neurotransmitters

Chauhan, Shailender Singh; Ojha, Sudarshan ; Mahmood, Akhtar

Abstract

Prolonged exposure to fluoride or alcohol affects brain. However, the understanding about their interactions and neurotoxicity following co-exposures is still poor. The present study was designed to assess oxidative stress, mitochondrial dysfunctions, acetylchonlineterase (AChE) activity, neurotransmitter levels and morphological alterations in brain of fluoride or/and ethanol fed rats. Six and eighteen month old animals received sodium fluoride (NaF, 25 mg/kg) and 30% ethanol (EtOH, 1 mL/kg) individually and in combination for 90 days. Brain showed elevation in oxidative stress with age and NaF/EtOH treatment. There was increased lipid peroxidation; decreased glutathione, total and protein thiol content; along with declined activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase under these conditions. Mitochondrial functions were impaired significantly with age and NaF/EtOH treatment. The activities of NADH dehydrogenase, succinate dehydrogenase and cytochrome c oxidase along with mitochondrial respiration rate were decreased whereas the levels of nitric oxide and citrulline were increased in treated animals. Administration of NaF/EtOH showed altered neurotransmitter levels and increased AChE activity in brain. The levels of dopamine and 5-hydroxytryptamine were decreased while 5-hydroxyindoleacetic acid and homovanillic acid were increased significantly. Histological examination showed morphological alterations in treated animals compared to controls. Interestingly, the observed effects were more pronounced in rats co-exposed to NaF and EtOH. It is concluded that neurotoxic effects of fluoride are age dependent and further amplified by alcohol co-administration. These effects are mediated through elevated oxidative stress, mitochondrial dysfunctions and impaired neurotransmitter functions

Keyword(s)

Acetylchonlineterase (AChE) activity, Fluoride-alcohol interactions

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