We aimed to investigate mitigating effects of N-acetylcysteine (NAC) on the oxidative stress, apoptosis and Parkinson's disease (PD)-related genes in the brain tissue of male rats exposed to continuous doses of cadmium and lead. Rats were randomly divided into five groups, including G1 (control), G2 (continuous dose of Cd), G3 (continuous dose of Pb), G4 (continuous dose of Cd + NAC), and G5 (continuous dose of Pb + NAC). Biomarkers of oxidative stress, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured. Expression of PD- and apoptosis-related genes was considered using RT-PCR. Chronic exposure to these heavy metals was associated with accumulation of Pb and Cd in the brain and blood and caused severe morphological changes in the brain, as well as decreased body and brain weights. Continuous exposure to Cd and Pb significantly decreased TAC content and SOD expression but increased MDA level in the brain tissues (P < 0.001). A significant increase was observed in expression of PD-related genes, Parkin, Pink1, LRRK2, SNCA, and Caspase-3 in the brain tissues following exposure to Cd and Pb. Pb exhibited stronger toxicity on the brain tissue compared to Cd. NAC supplementation not only improved morphological changes, but also compensated antioxidant capacity and expression of apoptosis- and PD-related genes in the brain tissues when compared to rats exposed to Pb and Cd alone. Chronic exposure to Pb and Cd is strongly associated with accumulation of these heavy metals in the brain, morphological changes, antioxidants depletion, oxidative stress, and brain cells apoptosis. Changes in expression of PD-related genes indicate the higher risk of PD among individuals who are chronically exposed to these heavy metals. NAC can protect brain tissue against Pb and Cd toxicity by elevating antioxidants capacity, mitigating oxidative stress, apoptosis, and down-regulating of PD-related genes.
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