Neurotoxicity and neurodegenerative disorders caused by pyrethroids: Adverse events, mechanisms of action and therapeutic approaches.

Abstract

Pyrethroid insecticides are extensively used worldwide and were initially considered to have low toxicity to non-target organisms. However, with the widespread application of Type I (non-cyano) and Type II (α-cyano) pyrethroids, evidence increasingly indicates that chronic exposure can induce neurological damage and risk of neurotoxicity and neurodegenerative disorders. This effect is primarily mediated through the disruption of voltage-gated sodium channels. Their lipophilic nature facilitates passage across the blood-brain barrier (BBB), where they can impair tight junctions increasing barrier permeability and creating a dual insult scenario that exacerbates neurotoxic effects. This review article synthesizes current knowledge on the roles and interrelationships of oxidative stress coupled with mitochondrial damage, autophagy dysregulation, neuroinflammation, and disturbances in voltage-gated ion channels within the context of pyrethroid-induced neurotoxicity. It examines the dual role of the BBB, which functions as both protector and target, and discusses the application of plant-derived natural extract for intervention. The analysis extends to the synergistic interactions among these pathophysiological mechanisms, highlights exposure risks for susceptible populations, and outlines current research challenges alongside future directions. This literature review manuscript offers novel insights and a valuable reference for the prevention and treatment of pyrethroid-induced neurotoxicity and related neurodegenerative disorders.