Ameliorative Effects of Ferulic Acid Against Lead Acetate-Induced Oxidative Stress, Mitochondrial Dysfunctions and Toxicity in Prepubertal Rat Brain

Epidemiological evidence has shown higher susceptibility of Children to the adverse effects of lead (Pb) exposure. However, experimental studies on Pb-induced neurotoxicity in prepubertal (PP) rats are limited. The present study aimed to examine the propensity of ferulic acid (FA), a commonly occurring phenolic acid in staple foods (fruits, vegetables, cereals, coffee etc.) to abrogate Pb-induced toxicity. Initially, we characterized Pb-induced adverse effects among PP rats exposed to Pb acetate (1,000-3,000 ppm in drinking water) for 5 weeks in terms of locomotor phenotype, activity of 5-aminolevulinic acid dehydratase (ALAD) in the blood, blood Pb levels and oxidative stress in brain regions. Further, the ameliorative effects of oral supplements of FA (25 mg/kg bw/day) were investigated in PP rats exposed to Pb (3,000 ppm). Pb intoxication increased the locomotor activity and FA supplements partially reversed the phenotype, while the reduced ALAD activity was also restored. FA significantly abrogated the enhanced oxidative stress in cerebellum (Cb) and hippocampus (Hc) as evidenced in terms of ROS generation, lipid peroxidation and protein carbonyls. Further, Pb-mediated perturbations in the glutathione levels and activity of enzymic antioxidants were also markedly restored. Furthermore, the protective effect of FA was discernible in striatum in terms of reduced oxidative stress, restored cholinergic activity and dopamine levels. Interestingly, reduced activity levels of mitochondrial complex I in Cb and enhanced levels in Hc among Pb-intoxicated rats were ameliorated by FA supplements. FA also decreased the number of damaged cells in cornu ammonis area CA1 and dentate gyrus as reflected by the histoarchitecture of Hc among Pb intoxicated rats. Collectively, our findings in the PP model allow us to hypothesize that ingestion of common phenolics such as FA may significantly alleviate the neurotoxic effects of Pb which may be largely attributed to its ability to abrogate oxidative stress.