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An investigation into the mechanism of toxicity of zinc oxide nanoparticles.
Sharma, Vyom
Sharma, Vyom
Publication Date
2012-04-19
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The University of Bradford theses are licenced under a Creative Commons Licence.
Peer-Reviewed
Open Access status
Accepted for publication
Institution
University of Bradford
Department
School of Life Sciences
Awarded
2011
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Abstract
The wide scale use of ZnO nanoparticles (NPs) in the world consumer
market has resulted in likelihood of exposure to human beings. The present
study was aimed to assess the in vitro and in vivo interactions of ZnO NPs in
the mammalian system and to elucidate the possible mechanism of their
toxicity.
Our in vitro results using human epidermal cells (A431), primary human
epidermal keratinocytes and human liver cells (HepG2) demonstrated that
cells exposed to ZnO NPs exhibit a decrease in cell viability which was
independent of NP dissolution. ZnO NPs also induced oxidative DNA
damage as evidenced by an increase in the Fpg sensitive sites. The reactive
oxygen species triggered a decrease in mitochondrial membrane potential
and an increase in the ratio of Bax/Bcl2 leading to apoptosis through the
intrinsic pathway. In addition, ZnO NPs induced phosphorylation of JNK, P38
and P53ser15. The results from our in vivo studies using a mouse model
showed that ZnO NPs induce lipid peroxidation, oxidative DNA damage and
apoptosis in liver which further confirmed our in vitro findings.
The data from the present study provide valuable insights into the cellular
interactions of ZnO NPs and the underlying molecular mechanism of their
toxicity. The results also stress the need for a comprehensive environmental
health and safety assessment of engineered nanomaterials to ensure safer
nanotechnology based products.
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Type
Thesis
Qualification name
PhD