title: Induction of oxidative stress, DNA damage and apoptosis in mouse liver after sub-acute oral exposure to zinc oxide nanoparticles.
abstract: Zinc oxide (ZnO) nanoparticles are finding applications in a wide range of products including cosmetics, food packaging, imaging, etc. This increases the likelihood of human exposure to these nanoparticles through dermal, inhalation and oral routes. Presently, the majority of the studies concerning ZnO nanoparticle toxicity have been conducted using in vitro systems which lack the complex cell-cell, cell-matrix interactions and hormonal effects found in the in vivo scenario. The present in vivo study in mice was aimed at investigating the oral toxicity of ZnO nanoparticles. Our results showed a significant accumulation of nanoparticles in the liver leading to cellular injury after sub-acute oral exposure of ZnO nanoparticles (300 mg/kg) for 14 consecutive days. This was evident by the elevated alanine aminotransferase (ALT) and alkaline phosphatase (ALP) serum levels and pathological lesions in the liver. ZnO nanoparticles were also found to induce oxidative stress indicated by an increase in lipid peroxidation. The DNA damage in the liver and kidney cells of mice was evaluated by the Fpg-modified Comet assay which revealed a significant (p<0.05) increase in the Fpg-specific DNA lesions in liver indicating oxidative stress as the cause of DNA damage. The TUNEL assay revealed an induction of apoptosis in the liver of mice exposed to ZnO nanoparticles compared to the control. Our results conclusively demonstrate that sub-acute oral exposure to ZnO nanoparticles in mice leads to an accumulation of nanoparticles in the liver causing oxidative stress mediated DNA damage and apoptosis. These results also suggest the need for a complete risk assessment of any new engineered nanoparticle before its arrival into the consumer market.
authors.affiliation: Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Vyom
authors.initials: V
authors.lastname: Sharma
authors.forename: Poonam
authors.initials: P
authors.lastname: Singh
authors.forename: Alok K
authors.initials: AK
authors.lastname: Pandey
authors.forename: Alok
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D020552:Comet Assay; D004249:DNA Damage; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D015034:Zinc Oxide