Today, nanoparticles (NPs) have been widely used in various fields. Manganese oxide nanoparticles have attracted a lot of attention due to many applications. One of the major concerns regarding the widespread use of various NPs is the exposure and accumulation in human organs and finally toxicity. The generation of reactive oxygen species (ROS) by mitochondria is one of the most important mechanisms of toxicity suggested by published studies induced by other NPs. However, limited studies have been conducted on the mechanism of toxicity of MnO2-NPs and MnO2-microparticles (MnO2-MPs). In this study, we compared the accumulation of MnO2-NPs and MnO2-MPs in different tissues and evaluated their effects on mitochondrial complexes in isolated mitochondria. Our results showed that intravascular (iv) administration of the MnO2-NPs in the same dose compared to the MnO2-MPs resulted in more accumulation in the C57 mouse female tissues. The effect of MnO2-NPs and MnO2-MPs in mitochondria showed that complexes I and III play an important role in increasing ROS generation and this effect is related to type of tissue. Also, our results showed that exposure to MnO2-NPs and MnO2-MPs reduced the activity of mitochondrial complexes II and IV. Our results suggest that the toxicity of the MnO2-NPs is higher than that of the MnO2-MPs and can lead to the depletion of antioxidant status, likely induction of apoptosis, cancer, and neurodegenerative disease. Abbreviations: NPs: nanoparticles; ROS: reactive oxygen species; SDH: succinate dehydrogenase; DCFH-DA: dichloro-dihydro-fluorescein diacetate; ELISA: enzyme-linked immunosorbent assay; MnO2-NPs: manganese oxide nanoparticles.
Keywords: MnO-MPs; MnO-NPs; ROS; mechanism; mitochondrial complexes; toxicity.