N-acetylcysteine modulates peripheral nerve excitability and conduction in a rat Model of chronic organophosphate exposure.

Chronic low-dose exposure to organophosphate pesticides has been associated with persistent peripheral neurotoxicity, yet the functional mechanisms underlying axonal dysfunction remain insufficiently defined. We investigated the effects of chronic diazinon exposure on peripheral nerve excitability and conduction properties in rats and evaluated the potential protective role of N-acetylcysteine (NAC). Adult male Wistar rats were allocated to four groups (n = 9 each): control (CON), diazinon (COP), combined treatment (COP+NAC), and NAC alone (NAC) for four weeks. Axonal excitability of the caudal nerve was assessed in vivo using threshold tracking, and sciatic nerve compound action potentials were recorded ex vivo with estimation of conduction velocity distributions. Diazinon exposure reduced rheobase and refractoriness, shortened the relative refractory period, increased superexcitability, and decreased the resting I/V slope, consistent with membrane depolarization and altered sodium channel function. Compound action potential amplitude and area were significantly reduced, accompanied by a shift toward slower-conducting fibers, indicating preferential impairment of fast axons. Concurrent NAC treatment partially normalized excitability parameters and attenuated conduction velocity shifts, while NAC alone produced mild hyperpolarizing changes. These findings indicate that chronic diazinon exposure disrupts axonal membrane properties and selectively affects fast-conducting fibers, and that NAC may mitigate these functional alterations.