Fisetin attenuates arsenic and fluoride subacute co-exposure induced neurotoxicity via regulating TNF- α mediated activation of NLRP3 inflammasome

Neurotoxicology. 2023 Jun 16:S0161-813X(23)00086-4. doi: 10.1016/j.neuro.2023.06.006. Online ahead of print.ABSTRACTGroundwater is considered safe, however, the occurrence of contaminants like arsenic and fluoride has raised a major healthcare concern. Clinical studies suggested that arsenic and fluoride co-exposure induced neurotoxicity, however efforts to explore safe and effective management of such neurotoxicity are limited. Therefore, we investigated the ameliorative effect of Fisetin against arsenic and fluoride subacute co-exposure-induced neurotoxicity, and associated biochemical and molecular changes. Male BALB/c mice Arsenic (NaAsO2: 50mg/L) and fluoride (NaF: 50mg/L) were exposed to drinking water and fisetin (5, 10, and 20mg/kg/day) was administered orally for 28 days. The neurobehavioral changes were recorded in the open field, rotarod, grip strength, tail suspension, forced swim, and novel object recognition test. The co-exposure resulted in anxiety-like behaviour, loss of motor coordination, depression-like behaviour, and loss of novelty-based memory, along with enhanced prooxidant, inflammatory markers and loss of cortical and hippocampal neurons. The treatment with fisetin reversed the co-exposure-induced neurobehavioral deficit along with restoration of redox & inflammatory milieu, and cortical and hippocampal neuronal density. Apart from antioxidants, inhibition of TNF-α/ NLRP3 expression has been suggested as one of the plausible neuroprotective mecha...
Source: Neurotoxicology - Category: Neurology Authors: Source Type: research