IN VIVO AND IN VITRO TOXICOLOGICAL STUDIES OF CO-EXPOSURE TO SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES AND SOLID LIPID NANOPARTICLES
1ALABI A. OKUNOLA*, 2SILVA H. ADNY, 3BAKARE A. ADEKUNLE, 2CRECZYNSKI-PASA B. TÂNIA
1Department of Biology, Federal University of Technology, Akure, Ondo State, Nigeria.
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2Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, P O Box 476, Florianópolis, SC 88040-900, Brazil.
3Cell Biology and Genetics Unit, Department of Zoology, University of Ibadan, Ibadan, Nigeria
Aim: To evaluate the possible cytogenotoxicity of co-exposure to Solid lipid nanoparticles (SLNs) and Superparamagnetic iron oxide nanoparticles (SPIONs), and the mechanism of action.
Background: Data on the toxicity of SLNs and SPIONs is insufficient, and no data exist on the toxicity of co-exposure to the two nanoparticles. In nature, human, animal and environment are co-exposed to different NPs at the same time from different sources.
Methods: In vitro cytotoxicity of SPIONs, SLNs and their 1:1 mixture using Alamar blue assay in NIH/3T3 (murine embryo fibroblast cells) cell line; and in vivo genotoxicity using murine bone marrow micronucleus assay were investigated. The molecular mechanisms underlining the induced cytogenotoxicity were studied through cell cycle analysis, detection of reactive oxygen species and alterations in mitochondrial membrane potential.
Results: The results showed that SPIONs has low cytotoxicity compared to SLNs. However, the mixture of SPIONs and SLNs showed synergistic effect in NIH/3T3. In mice, there was a significant increase (p<0.05) in micronucleated polychromatic erythrocytes (MNPCE) and nuclear abnormalities (NA) in SPIONs, SLNs and their mixture treated mice. The mixture induced the highest frequency of MNPCE and NA. Apoptosis triggered by reactive oxygen species increase and disturbances in mitochondrial membrane potential were the probable mechanisms of action.
Conclusion: Co-exposure to SLNs and SPIONs nanoparticles is more cytogenotoxic than the individual nanoparticle,hence, care should be taken in human exposure to multiple nanoparticles from different consumer products.