Protocatechuic acid mitigates cadmium-induced neurotoxicity in rats: Role of oxidative stress, inflammation and apoptosis
Environmental and occupational exposure to heavy metals, including cadmium (Cd), is associated with extremely
adverse impacts to living systems. Antioxidant agents are suggested to eliminate Cd intoxication. In
this paper, we investigated the potential neuroprotective effect of protocatechuic acid (PCA) against Cdinduced
neuronal damage in rats. Adult male Wistar rats were randomly divided into control, PCA
(100 mg/kg)-treated, CdCl2 (6.5 mg/kg)-treated, and PCA and Cd treatment groups. Pre-treatmentwith PCA significantly
reduced Cd concentrations and increased cortical acetylcholinesterase activity and brain derived neurotrophic
factor. Additionally, PCA also prevented CdCl2-induced oxidative stress in the cortical tissue by
preventing lipid peroxidation and the formation of nitric oxide (NO), and significantly enhancing antioxidant enzymes.
Molecularly, PCA significantly up-regulated the antioxidant gene expression (Sod2, Cat, Gpx1, and Gsr)
that was down-regulated by Cd. It should be noted that this effect was achieved by targeting the nuclearrelated
factor 2 (Nfe2l2) mRNA expression. PCA also prevented the Cd-induced inflammation by reducing the
pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β. Moreover, PCA supplementation
relieved the Cd-induced neuronal death by increasing Bcl-2 and decreasing Bax and Cas-3 levels in the cortical
tissue. The improvement of the cortical tissue histopathology by PCA confirmed the biochemical and
Science of the Total Environment 723 (2020) 137969
⁎ Corresponding authors.
E-mail addresses: eolayan@ksu.edu.sa (E.M. Al Olayan), aest1977@hotmail.com (A.E. Abdel Moneim).
https://doi.org/10.1016/j.scitotenv.2020.137969
0048-9697/© 2018 Published by Elsevier B.V.
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