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.