title: Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles.
abstract: The use of amorphous silica (SiO2) in biopharmaceutical and industrial fields can lead to human exposure by injection, skin penetration, ingestion, or inhalation. However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs) on multiple organs and the mechanisms underlying these effects are not well understood. Presently, we investigated the acute (24 hours) effects of intraperitoneally administered 50 nm SiNPs (0.25 mg/kg) on systemic toxicity, oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney, and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the lung, liver, kidney, and brain, but was not changed in the heart. Similarly, superoxide dismutase and catalase activities were significantly affected by SiNPs in all organs studied. While the concentration of tumor necrosis factor α was insignificantly increased in the liver and brain, its increase was statistically significant in the lung, heart, and kidney. SiNPs induced a significant elevation in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver, and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed by comet assay, in all the organs studied. SiNPs caused leukocytosis and increased the plasma activities of lactate dehydrogenase, creatine kinase, alanine aminotranferase, and aspartate aminotransferase. These results indicate that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs, and highlight the need for thorough evaluation of SiNPs before they can be safely used in human beings.
authors.affiliation: Department of Physiology, United Arab Emirates University, Al Ain, UAE, Sultanate of Oman.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Nemmar
authors.affiliation: Department of Physiology, United Arab Emirates University, Al Ain, UAE, Sultanate of Oman.
authors.forename: Priya
authors.initials: P
authors.lastname: Yuvaraju
authors.affiliation: Department of Physiology, United Arab Emirates University, Al Ain, UAE, Sultanate of Oman.
authors.forename: Sumaya
authors.initials: S
authors.lastname: Beegam
authors.affiliation: Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE, Sultanate of Oman.
authors.forename: Javed
authors.initials: J
authors.lastname: Yasin
authors.affiliation: Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE, Sultanate of Oman.
authors.forename: Elsadig E
authors.initials: EE
authors.lastname: Kazzam
authors.affiliation: Department of Pharmacology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Al-Khoudh, Sultanate of Oman.
authors.forename: Badreldin H
authors.initials: BH
authors.lastname: Ali
mesh_terms: D000818:Animals; D004249:DNA Damage; D007249:Inflammation / Q000139:chemically induced; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D009928:Organ Specificity; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry* / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D012822:Silicon Dioxide; D013482:Superoxide Dismutase
keywords: DNA damage; amorphous silica nanoparticles; inflammation; organ toxicity; oxidative stress