High-Frequency, Low-Intensity Pulsed Electric Field and N-Acetylcysteine Synergistically Protect SH-SY5Y Cells...

Area of Science:

• Neuroscience
• Biochemistry
• Cell Biology

Background:

• Oxidative stress is a key factor in neurodegenerative diseases (NDDs).
• N-acetylcysteine (NAC) exhibits antioxidant properties, making it a potential therapeutic agent.
• Novel therapeutic strategies are needed to combat oxidative damage in neuronal cells.

Purpose of the Study:

• To investigate the synergistic neuroprotective effects of combining NAC with high-frequency, low-intensity pulsed electric field (H-LIPEF) stimulation.
• To evaluate the combined treatment's impact on oxidative stress and apoptosis in neuronal cells.
• To elucidate the underlying molecular mechanisms of the combined neuroprotection.

Main Methods:

• SH-SY5Y human neuronal cells were subjected to hydrogen peroxide (H₂O₂)-induced oxidative damage.
• Cells were pretreated with NAC and exposed to H-LIPEF stimulation.
• Cell viability, mitochondrial apoptosis, reactive oxygen species levels, and DNA damage markers were assessed.
• Key signaling pathway components, including p-Akt, Nrf2, SOD2, and MTH1, were analyzed.

Main Results:

• Combined NAC and H-LIPEF treatment significantly reduced oxidative stress and improved cell viability.
• The combination therapy more effectively inhibited mitochondrial apoptosis compared to individual treatments.
• Mechanistic studies revealed decreased superoxide and intracellular H₂O₂ levels.
• Enhanced activation of the p-Akt/Nrf2/SOD2 pathway and reduced oxidative DNA damage (8-oxo-dG) were observed, alongside elevated MTH1 expression.

Conclusions:

• H-LIPEF stimulation potentiates the neuroprotective effects of low-dose NAC.
• The combination therapy offers a promising strategy for mitigating oxidative stress and DNA damage in neurodegenerative diseases.
• This synergistic approach warrants further investigation as a novel therapeutic intervention for NDDs.