Aggregated amyloid peptides (AP), major components of senile plaques, have been considered to play a very important and crucial role in the development and neuro-pathogenesis of Alzheimer’s disease (AD). In the present in vitro, study the synergistic effects of Pb2+, a heavy metal, and AP on the human neuroblastoma SH-SY5Y cells were investigated. The cells treated with Pb2+ (0.01–10 μM) alone exhibited a significant decrease in viability and IC50 was 5 μM. A similar decrease in viability was also observed when the cells were exposed to AP, Aβ1–40 (20–120 μM) and Aβ25-35 (2.5–15 μM) for 48 hrs. The IC50 values were 60 μM and 7.5 μM for Aβ1–40 and Aβ25–35 respectively. To assess the synergistic effects the cells were exposed to IC50 of both AP and Pb2+, which resulted in further reduction of the viability. The study was extended to determine the lactate dehydrogenase (LDH) release to assess the cytotoxic effects, 8-isoprostane for extent of oxidative damage, COX 1 and 2 for inflammation related changes, p53 protein for DNA damage and protein kinases A and C for signal transduction. The data suggest that the toxic effects of AP were most potent in the presence of Pb2+, resulting in an aggravated clinical pathological condition. This could be attributed to the oxidative stress, inflammation neuronal apoptosis and an alteration in the activities of the signaling enzymes.
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