Toxic effects of Acetamiprid on the human microglial cell line HMC3

Acetamiprid (ACE), a second-generation neonicotinoid insecticide, is one of the most widely utilized pesticides globally. Recently, neonicotinoids have faced increasing scrutiny due to their potential mammalian neurotoxicity and their role as metabolism-disrupting chemicals (MDCs). Emerging evidence suggests that ACE can impair the functionality of microglia - the resident macrophages of the central nervous system (CNS), disrupting brain homeostasis, neuroinflammatory balance, and neurodevelopment. This study aimed to investigate the direct toxic effects of ACE at environmentally relevant doses on the human microglial cell line clone 3 (HMC3), under both basal and lipopolysaccharide (LPS)-induced inflammatory conditions. Furthermore, we evaluated the protective potential of protocatechuic acid (PCA), a bioactive phenolic compound found in edible plants and a major secondary metabolite of anthocyanins and other flavonoids. PCA is considered a promising neuroprotective candidate due to its potent antioxidant properties and its ability to cross the blood-brain barrier (BBB). Our findings demonstrate that ACE exposure, even at low concentrations (150nM), alters human microglial physiology, compromising both cellular viability and functional homeostasis. These results underscore the significant neurotoxic risk associated with ACE. Notably, PCA failed to counteract ACE-induced damage under our experimental conditions, despite its established anti-inflammatory properties.