Engineered nanoparticles have been extensively explored in various biomedical settings including nanoparticulate imaging agents due to its promising benefits to mankind. Iodine-intolerance patients have caused alarming concerns in searching new contrast media with lower toxicity effect. However, proper potential mechanism of nanoparticles has yet to be fully established despite its early acceptance and emerging usage. By using animal model system, our aim is to assess acute toxicity of 14 nm iron oxide nanoparticles (IONPs) coated with citric acid, nitric acid, perchloric acid and silane-polyethylene glycol (SiPEG). Eighteen male Wistar Rats were used in order to explore the underlying toxicity of IONPs in liver tissues after 24 hours. Hydroxyl radicals (˙OH) were elucidated by using reactive oxygen species (ROS) production assay and western blotting for the presence of p53 protein expression. The results revealed SiPEG coated IONPs have lower ROS production and lower expression of p53, however no statistical significant were observed. It can be hypothesized that SiPEG has blood-pooling contrast agent potential due to longer circulation period in blood. While, IONPs not coated with SiPEG tend to be phagocytosed by mononuclear phagocyte system and released Fe2+ ions initiative to acute cellular toxicity. The outcomes highlighted that administration of SiPEG coated IONPs believed to be a safer radiographic contrast media.