Cadmium chloride exposure impairs the growth and behavior of Drosophila via ferroptosis

Cadmium (Cd) is a widely distributed toxic heavy metal that enters the environment via anthropogenic mobilization and accumulates in plants and animals, causing metabolic abnormalities even mortality. Although the toxic effects and stress damage of cadmium have been investigated extensively over the past few decades, research on its ability to trig-ger ferroptosis, growth retardation, and behavioral abnormalities is insufficient. As a result, the effects of CdCl2 expo-sure on growth and development, activity and sleep, and ferroptosis in this study were examined in fruit fly (Drosophila melanogaster). When exposed to 0.5 mM CdCl2, the entire growth period from larvae to adults was prolonged, and the rates of pupation and eclosion were decreased. Additionally, CdCl2 exposure resulted in a decrease in body weight and individual size of fruit fly and high lethality rate. Moreover, CdCl2 exposure altered fruit fly behavior, including de-creased activity and increased sleep duration, particularly in females. Ferrostatin-1 (Fer-1) is a potent selective ferrop-tosis inhibitor that effectively slows lipid hydroperoxide accumulation to rescue body size reduction and restore activity and sleep in CdCl2-exposed female flies. CdCl2 exposure could induce ferroptosis in fruit fly mechanistically, as evidenced by inhibition of Nrf2 signaling pathway, accumulation of lipid peroxidation, impairment of GPX4 antiox-idant system, and upregulation of iron metabolism. Our findings suggest that Cd exposure triggers ferroptosis, which leads to growth retardation and behavioral disorders in fruit fly.