title: Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation.
abstract: Amorphous silica nanoparticles (SiNPs) are being used in biomedical, pharmaceutical, and many other industrial applications entailing human exposure. However, their potential vascular and systemic pathophysiologic effects are not fully understood. Here, we investigated the acute (24 hours) systemic toxicity of intraperitoneally administered 50 nm and 500 nm SiNPs in mice (0.5 mg/kg). Both sizes of SiNPs induced a platelet proaggregatory effect in pial venules and increased plasma concentration of plasminogen activator inhibitor-1. Elevated plasma levels of von Willebrand factor and fibrinogen and a decrease in the number of circulating platelets were only seen following the administration of 50 nm SiNPs. The direct addition of SiNPs to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced with 50 nm SiNPs. Both sizes of SiNPs increased lactate dehydrogenase activity and interleukin 1β concentration. However, tumor necrosis factor α concentration was only increased after the administration of 50 nm SiNPs. Nevertheless, plasma markers of oxidative stress, including 8-isoprostane, thiobarbituric acid reactive substances, catalase, and glutathione S-transferase, were not affected by SiNPs. The in vitro exposure of human umbilical vein endothelial cells to SiNPs showed a reduced cellular viability, and more potency was seen with 50 nm SiNPs. Both sizes of SiNPs caused a decrease in endothelium-dependent relaxation of isolated small mesenteric arteries. We conclude that amorphous SiNPs cause systemic inflammation and coagulation events, and alter vascular reactivity. Overall, the effects observed with 50 nm SiNPs were more pronounced than those with 500 nm SiNPs. These findings provide new insight into the deleterious effect of amorphous SiNPs on vascular homeostasis.
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Nemmar
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod, Sultanate of Oman.
authors.forename: Sulayma
authors.initials: S
authors.lastname: Albarwani
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Sumaya
authors.initials: S
authors.lastname: Beegam
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Priya
authors.initials: P
authors.lastname: Yuvaraju
authors.affiliation: Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Javed
authors.initials: J
authors.lastname: Yasin
authors.affiliation: Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Samir
authors.initials: S
authors.lastname: Attoub
authors.affiliation: Department of Pharmacology, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khod, Sultanate of Oman.
authors.forename: Badreldin H
authors.initials: BH
authors.lastname: Ali
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008297:Male; D008422:Materials Testing; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011921:Rats, Inbred WKY; D012822:Silicon Dioxide / Q000633:toxicity*; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced* / Q000276:immunology*; D013927:Thrombosis / Q000139:chemically induced* / Q000276:immunology*
chemical_list: D012822:Silicon Dioxide
keywords: amorphous silica nanoparticles; systemic inflammation; thrombosis; toxicity