Fluoride is the second largest contaminant of drinking water. Fluoride toxicity is a major concern in the endemic areas where a high amount of fluoride is present in ground water. Oxidative stress has been proposed to be one of the mechanisms of fluoride-induced toxicity. Antioxidant-rich food has been found to alleviate fluoride-induced toxicity. Therefore, in this study, we have examined the effect of hesperidin on fluoride-induced neurobehavioral changes in rats. In the current study, male Sprague-Dawley rats were exposed to sodium fluoride through drinking water (120 ppm). Hesperidin (200 mg kg-1 d-1 ; per os) was administered either alone or in combination with fluoride-containing drinking water. Bisphinol A diglycidyl ether (BADGE) was used as peroxisome proliferator-activated receptor-? (PPAR-?) antagonist and was administered (10 mg kg-1 d-1 ; intraperitoneal injection) with/without hesperidin along with fluoride-containing drinking water. The behavioral changes in the animals were assessed by analyzing rotarod test, novel object recognition test, and forced swim test (FST). After 8 weeks, animals were killed to isolate blood and brain for monitoring biochemical changes. The 8-week exposure of fluoride resulted in motor impairment as observed with reduced fall time in rotarod test, memory impairment as observed with reduced preference index in novel object recognition test, and depression-like behavior as observed with reduced mobility index in the FST. Treatment with hesperidin improved neurobehavioral impairment along with restoration in brain biochemical changes (ie, acetylcholinesterase activity and antioxidant and oxidative stress parameters). The protective effect of hesperidin was reversed by coadministration of BADGE. The neuroprotective effect of hesperidin appears to be contributed through PPAR-? receptor.
Keywords: PPAR-? receptor; fluoride toxicity; hesperidin; neurotoxicity; oxidative stress.
*Original abstract online at https://doi.org/10.1002/jbt.22575