The effects of nano-sized PbO on biomarkers of membrane disruption and DNA damage in a sub-chronic inhalation study on mice
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- 8-OHdG, 8-isoPGE isoprostanes, 8-isoPGF2α, LC-MS/MS, Oxidative damage, TBARS, inhalation, lead, lipid peroxidation, nanoparticle,
- MeSH
- Biomarkers metabolism MeSH
- Inhalation Exposure adverse effects analysis MeSH
- Liver drug effects metabolism MeSH
- Kidney drug effects metabolism MeSH
- Humans MeSH
- Membrane Lipids metabolism MeSH
- Brain drug effects metabolism MeSH
- Mice, Inbred ICR MeSH
- Mice MeSH
- Nanoparticles metabolism toxicity MeSH
- Lead metabolism toxicity MeSH
- Oxidation-Reduction MeSH
- Oxidative Stress drug effects MeSH
- Oxides metabolism toxicity MeSH
- Lipid Peroxidation drug effects MeSH
- Lung drug effects metabolism MeSH
- DNA Damage * MeSH
- Toxicity Tests, Subchronic MeSH
- Inflammation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Biomarkers MeSH
- lead oxide MeSH Browser
- Membrane Lipids MeSH
- Lead MeSH
- Oxides MeSH
Although the production of engineered nanoparticles increases our knowledge of toxicity and mechanisms of bioactivity during relevant exposures is lacking. In the present study mice were exposed to PbO nanoparticles (PbONP; 192.5 µg/m3; 1.93 × 106 particles/cm3) for 2, 5 and 13 weeks through continuous inhalation. The analyses addressed Pb and PbONP distribution in organs (lung, liver, kidney, brain) using electrothermal atomic absorption spectrometry and transmission electron microscopy, as well as histopathology and analyses of oxidative stress biomarkers. New LC-MS/MS methods were validated for biomarkers of lipid damage F2-isoprostanes (8-iso-prostaglandins F2-alpha and E2) and hydroxylated deoxoguanosine (8-OHdG, marker of DNA oxidation). Commonly studied malondialdehyde was also measured as TBARS by HPLC-DAD. The study revealed fast blood transport and distribution of Pb from the lung to the kidney and liver. A different Pb accumulation trend was observed in the brain, suggesting transfer of NP along the nasal nerve to the olfactory bulbs. Long-term inhalation of PbONP caused lipid peroxidation in animal brains (increased levels of TBARS and both isoprostanes). Membrane lipid damage was also detected in the kidney after shorter exposures, but not in the liver or lung. On the contrary, longer exposures to PbONP increased levels of 8-OHdG in the lung and temporarily increased lung weight after 2 and 5 weeks of exposure. The histopathological changes observed mainly in the lung and liver indicated inflammation and general toxicity responses. The present long-term inhalation study indicates risks of PbONP to both human health and the environment.
Faculty of Medicine Department of Histology and Embryology Masaryk University Brno Czech Republic
Faculty of Science Institute of Experimental Biology Masaryk University Brno Czech Republic
Faculty of Science RECETOX Masaryk University Brno Czech Republic
Institute of Analytical Chemistry Czech Academy of Sciences Brno Czech Republic
Institute of Animal Physiology and Genetics Czech Academy of Sciences Brno Czech Republic
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