Neuroprotective Role of Levetiracetam against Lead-Induced GSTM1 Inhibition

Alzheimer’s disease (AD) is the most common form of
dementia and a major global health challenge.
Environmental exposure to lead (Pb) has been
implicated as a risk factor due to its ability to induce
oxidative stress and disrupt neuronal homeostasis. The
present study investigated the neuroprotective role of
levetiracetam (LEV) against lead acetate-induced
toxicity in SH-SY5Y neuroblastoma cells, with a focus
on glutathione S-transferase Mu 1 (GSTM1) inhibition.
Catalase (CAT) activity was assessed following 24 h
treatment with lead acetate (10 µM) and varying
concentrations of LEV (100–1000 µg/mL). Lead
exposure significantly reduced CAT activity, while LEV
treatment restored antioxidant function in a dosedependent manner, with near normalization at 1000
µg/mL. In silico molecular docking demonstrated lead
acetate bound GSTM1 with a binding energy of –3.1
kcal/mol and an inhibition constant (Ki) of 5.24 mM,
suggesting potential inhibitory effects on the enzyme.
Hydrogen bond interactions with key amino acid
residues supported the predicted interference of lead
with GSTM1 function.