The Potent Role of Thymoquinone in Neutralizing Iron Oxide Nanoparticles’ Toxicity
The emergence of nanoparticles in the field of medicine has been a significant leap forward, promising unprecedented advancements in disease diagnosis and therapy. Iron oxide nanoparticles (IONPs) are one such class of nanoparticles that have been increasingly recognized for their applications in magnetic resonance imaging (MRI) and cancer theranostics. However, their biocompatibility and potential toxicological impacts on both human health and the environment have been subjected to intense scrutiny. A recent study, published in Scientific Reports, has shed new light on this safety aspect, evaluating the DNA-damaging and oxidative stress-inducing effects of IONPs in vivo and in vitro, with a possible mitigation strategy offered by thymoquinone (DOI: 10.1038/s41598-019-43188-5).
Reactive Oxygen Species: A Double-Edged Sword in Nanomedicine
Reactive oxygen species (ROS) generation is a critical determinant of nanoparticle-induced cytotoxicity. IONPs, due to their high reactivity, can lead to the excessive production of ROS, causing cellular damage, genotoxicity, and apoptosis in various cells, including normal cell lines. The oxidative stress resultant from ROS overload has been implicated in the pathogenesis of numerous diseases, bringing to the forefront the urgency to address this potential side effect of IONPs.
The aforementioned study, spearheaded by a team from Aligarh Muslim University, meticulously explored the interaction of IONPs with cellular DNA and assessed their toxicological effects in primary lymphocytes of Wistar rats and in vivo in these rats. Characterization of IONPs using state-of-art techniques such as Transmission Electron Microscopy (TEM), Scanning Electron Microscopy with Energy Dispersive X-ray Spectroscopy (SEM-EDS), and X-ray Diffraction (XRD) facilitated a comprehensive understanding of their biochemical interaction profiles with DNA. The alarming finding that IONPs not only form complex structures with DNA but also intercalate between DNA base pairs unveils a mechanism through which these nanoparticles may exert genotoxic effects.
Descending into a Cellular Crisis: IONPs Propel DNA and Oxidative Damage
The in vitro segment of the research demonstrated a worrying dose-dependent decrease in rat lymphocyte viability upon exposure to increasing concentrations of IONPs. This detrimental effect paralleled the observed dose-dependent uptick in ROS generation, suggesting a causative link between elevated ROS and cellular death.
The in vivo arm of the study painted an equally concerning picture. Wistar rats administered with varying doses of IONPs exhibited dose-dependent genetic damage, manifesting as decreased enzymatic activity of antioxidants and increased lipid peroxidation – a hallmark of oxidative stress. These findings corroborate the hypothesis that IONPs-induced genotoxicity in vivo may be a repercussion of the oxidative stress inflicted by unleashed ROS.
Thymoquinone: A Promising Protectors Against Nanoparticle Assault
Enter thymoquinone – a phytochemical known for its potent antioxidant properties. Found in the seeds of Nigella sativa, also known as black cumin, thymoquinone has been investigated for its therapeutic potential, including its anti-inflammatory, anticancer, and antioxidative stress activities. In this investigation, thymoquinone played a notably significant role in mitigating the DNA and oxidative damage inflicted by IONPs both in vitro and in vivo. The supplementation of thymoquinone alongside IONPs treatment yielded a marked reduction in genetic damage and lipid peroxidation, as well as restored antioxidant enzyme activities, indicative of its protective effect against the onslaught of IONPs.
Implications and Future Directions
This groundbreaking study has profound implications for the future of nanomedicine, particularly in safely harnessing the therapeutic potential of IONPs. By identifying the genotoxicity profile of IONPs and offering a natural antidote in the form of thymoquinone, it paves the way for safer biomedical applications of nanoparticles.
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References
1. Ansari, M. O., Parveen, N., Ahmad, M. F., Wani, A. L., Afrin, S., … Tabish, M. (2019). Evaluation of DNA interaction, genotoxicity and oxidative stress induced by iron oxide nanoparticles both in vitro and in vivo: attenuation by thymoquinone. Scientific Reports, 9, 6912. doi: 10.1038/s41598-019-43188-5
2. Gupta, A. K., & Gupta, M. (2005). Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials, 26(18), 3995-4021. doi:10.1016/j.biomaterials.2004.10.012
3. Singh, N., et al. (2009). NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials, 30(23-24), 3891-3914. doi:10.1016/j.biomaterials.2009.04.009
4. Ahamed, M., et al. (2013). Iron oxide nanoparticle-induced oxidative stress and genotoxicity in human skin epithelial and lung epithelial cell lines. Current Pharmaceutical Design, 19(37), 6681-6690. doi:10.2174/1381612811319370011
5. Freitas, M. L. L., et al. (2002). A double-coated magnetite-based magnetic fluid evaluation by cytometry and genetic tests. Journal of Magnetism and Magnetic Materials, 252, 396-398. doi:10.1016/S0304-8853(02)00655-8
Keywords
1. Iron Oxide Nanoparticles
2. Thymoquinone Benefits
3. Oxidative Stress Reduction
4. Nanoparticle Toxicity Mitigation
5. Genotoxicity and Antioxidants