Physiological and Behavioral Effects of Chronic Diethylpropion Exposure During Development in Caenorhabditis elegans:...

Diethylpropion (DEP), a psychostimulant structurally related to amphetamine, is prescribed as an appetite suppressant but carries a potential risk of neurotoxicity and abuse. Here, we investigated the physiological and behavioral consequences of chronic DEP exposure during development in Caenorhabditis elegans, combining in vivo assays with in silico toxicity predictions. Age-synchronized larvae were exposed to DEP (100-500 μM) for up to 72 h, and survival, growth, reproduction, feeding, and neuromotor function were assessed. DEP reduced survival in a dose-dependent manner, delayed larval development, decreased body size, and impaired reproductive capacity, including brood size reduction, shorter egg-laying period, and increased intrauterine egg retention. Neuromotor activity, measured by head thrashes and body bends, as well as pharyngeal pumping rates, was significantly reduced. DEP also triggered oxidative stress, evidenced by upregulation of gst-4::GFP expression. In silico analysis predicted high neurotoxicity, oxidative stress potential, and endocrine disruption, with probable interactions in dopaminergic signaling and mitochondrial function. These findings indicate that developmental DEP exposure disrupts multiple physiological systems in C. elegans, highlighting its potential to cause lasting neuromuscular and reproductive impairments.