Ferrocene-derived magnetic fiber-particles from diesel exhaust: enhanced pulmonary toxicity via Bach1-SAT1-polyamine depletion

Abstract

Background and aim: Magnetic nanoparticles are key components of air pollution. The combustion of diesel engine fuels, especially with ferrocene doping to reduce emissions, may increase exposure to these particles and related health risks. This study aimed to reveal the generation and characterization of ferrocene-derived magnetic particles (FMP) in ferrocene-doped diesel exhaust, and to investigate its toxicities and associated mechanisms in an avian model. Methods: FMP was observed in ferrocene-doped diesel exhaust particles, and extracted with neodymium magnets. Extracted FMP was characterized, and exposed to hatchling chickens via aerosol inhalation. Pulmonary toxicities were assessed with pathological and molecular methods. Associated mechanisms were investigated with RNA-seq, in vitro cell culture, and in vivo gene silencing. Results: FMP was characterized to be fibrous, magnetic iron-containing carbon particles. Extracted FMP could directly induce pulmonary toxicity. Mechanistic investigations revealed molecular mechanism associated with ferroptosis via Bach1, SAT1 and polyamines depletion, and further confirmed with ferroptosis inhibitor treatment, Bach1 inhibitor treatment, supplementation of polyamines or SAT1 silencing. Conclusions: Ferrocene doping could result in formation of magnetic particles in diesel exhaust. For the first time, magnetic fiber-like particles were extracted from ferrocene-doped DE particles, which is a potential source of magnetic particles in air pollution. To better balance emission control and health effects, further investigations are necessary.