Abstract
Heavy metal exposure, in lead (Pb) particularly, is associated with severe neuronal impairment though oxidative stress mediated by reactive oxygen species, and antioxidants may be used to abolish these adverse effects. This study investigated the potential neuroprotective role of coenzyme Q10 (CoQ10) against lead acetate (PbAc)-induced neurotoxicity. Twenty-eight male Wistar albino rats were divided into four equal groups (n = 7) and treated as follows: the control group was injected with physiological saline (0.9% NaCl); the CoQ10 group was injected with CoQ10 (10 mg/kg); PbAc group was injected with PbAc (20 mg/kg); PbAc + CoQ10 group was injected first with PbAc, and after 1 h with CoQ10. All groups were injected intraperitoneally for seven days. PbAc significantly increased cortical lipid peroxidation, nitrate/nitrite levels, and inducible nitric oxide synthase expression, and decreased glutathione content, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase activity and mRNA expression, as well as nuclear factor erythroid 2–related factor 2 (Nrf2) and homoxygenase-1 (HO-1) expression. PbAc also promoted the secretion of interleukin-1ß and tumor necrosis factor-α, inhibited interleukin-10 production, triggered the activation of pro-apoptotic proteins, and suppressed anti-apoptotic proteins. Additionally, PbAc increased the cortical levels of serotonin, dopamine, norepinephrine, GABA, and glutamate, and decreased the level of ATP. However, treatment with CoQ10 rescued cortical neurons from PbAc-induced neurotoxicity by restoring the balance between oxidants and antioxidants, activating the Nrf2/HO-1 pathway, suppressing inflammation, inhibiting the apoptotic cascade, and modulating cortical neurotransmission and energy metabolism. Altogether, our findings indicate that CoQ10 has beneficial effects against PbAc-induced neuronal damage through its antioxidant, anti-inflammatory, anti-apoptotic, and neuromodulatory activities.
Highlights
Exposure to heavy metals is a major health concern worldwide due to their long biological half-lives and irreversible effects on different body systems [1]
Duncan’s changes compared with the with the control group; b significant changes compared with the PbAc injected group. mRNA
Control group; b significant changes compared with the PbAc injected group. mRNA expression data expression data are expressed as the mean ± standard deviation (SD) of triplicate assays normalized to β-actin and are expressed as the mean ± SD of triplicate assays normalized to β-actin and expressed as fold changes expressed as fold changes compared with the mRNA levels of the control group
Summary
Exposure to heavy metals is a major health concern worldwide due to their long biological half-lives and irreversible effects on different body systems [1]. Lead (Pb), a naturally-distributed heavy metal found mainly in combination with sulfur, is characterized by poor conductivity, malleability, high density, and resistance to corrosion. These physio-chemical properties have meant that Pb is widely used in a variety of industries. Humans are mainly exposed to Pb through the ingestion and inhalation. Res. Public Health 2019, 16, 2895; doi:10.3390/ijerph16162895 www.mdpi.com/journal/ijerph
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