Toxicological alterations induced by subacute exposure of silver nanoparticles in Wistar rats

Silver nanoparticles (AgNPs) have become crucial players in the field of medicine and various other industries. AgNPs have a wide array of applications, which includes production of electronic goods, cosmetics, synthesis of dyes, and printing inks, as well as targeted delivery of drugs to specialized cells inside the body. Even though humans readily come in contact with these particles, the organ-specific accumulation and resulting mechanisms of toxicity induced by inhaled AgNPs are still under investigation. The goal of this study was to determine the organ distribution of inhaled AgNPs and investigate the resulting systemic toxicity. To do this, male Wistar rats were exposed by inhalation to AgNPs for 4 hr/day (200 parts per billion/day) for five consecutive days. The nanoparticles were generated using a laser ablation technique using a soft-landing ion mobility (SLIM) instrument. Inductively coupled plasma mass spectrometric (ICP-MS) analysis showed organ-specific accumulation of the nanoparticles, with the highest concentration present in the lungs, followed by the liver and kidneys. Nanoparticle distribution was characterized in the organs using scanning electron microscopy (SEM) and matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) imaging. Bone marrow cytotoxicity assay of the cells from the femur of rats showed micronuclei formation and signs of cellular cytotoxicity. Moreover, rats displayed increased levels of circulating lactate and glutathione disulphide (GSSG), as determined by liquid chromatography-mass spectrometry (LC-MS) analysis. Collectively, our observations suggest that inhaled subacute exposure to AgNP results in accumulation of AgNPs in the lungs, liver, and kidneys, preferentially, as well as mediates induced systemic toxicity.