Biomarkers of oxidative stress for in vivo assessment of toxicological effects of iron oxide nanoparticles

Iron oxide nanoparticles (Fe₂O₃-IONPs) have revolutionized the industry by significant economic and scientific impacts. Enormous increase in the usage of IONPs has raised concerns about their unseen adverse effects. In the current study, we investigated the effects of IONPs and its bulk on oxidative stress biomarkers, histopathology and biodistribution in rats after 28 days repeated oral treatment at 30, 300 and 1000 mg/kg body weight (b.w.). IONPs size in dry, wet forms and crystallinity was determined using TEM, DLS and XRD. The investigation of oxidative stress biomarkers demonstrated significant increase in lipid peroxidation and decrease in reduced glutathione content in the liver, kidney and the brain of the treated groups in a dose dependant manner. Further, antioxidant enzymes catalase, glutathione S transferase, glutathione peroxidase and glutathione reductase activities were significantly elevated along with significant decrease in superoxide dismutase activity in treated rat organs. ICP-OES analysis revealed dose and size dependant accumulation of IONPs in the liver followed by kidney and the brain than bulk. Moreover, accumulation of IONPs at high dose brought pathological changes only in liver. A large fraction of IONPs was eliminated in urine. Bulk material was substantially excreted in faeces than IONPs suggesting increased absorption of IONPs. In conclusion accumulated IONPs and bulk in organs trigger free radical generation, leading to the induction of oxidative stress condition in rats. The results obtained highlight the importance of toxicity assessments in evaluating the efficiency of IONPs for the safe implementation for diversified applications.