Amorphous nanosilicas induce consumptive coagulopathy after systemic exposure.
We previously reported that well-dispersed amorphous nanosilicas with particle size 70 nm (nSP70) penetrate skin and produce systemic exposure after topical application. These findings underscore the need to examine biological effects after systemic exposure to nanosilicas. The present study was designed to examine the biological effects. BALB/c mice were intravenously injected with amorphous nanosilicas of sizes 70, 100, 300, 1000 nm and then assessed for survival, blood biochemistry, and coagulation. As a result, injection of nSP70 caused fatal toxicity, liver damage, and platelet depletion, suggesting that nSP70 caused consumptive coagulopathy. Additionally, nSP70 exerts procoagulant activity in vitro associated with an increase in specific surface area, which increases as diameter reduces. In contrast, nSP70-mediated procoagulant activity was absent in factor XII-deficient plasma. Collectively, we revealed that interaction between nSP70 and intrinsic coagulation factors such as factor XII, were deeply related to nSP70-induced harmful effects. In other words, it is suggested that if interaction between nSP70 and coagulation factors can be suppressed, nSP70-induced harmful effects may be avoided. These results would provide useful information for ensuring the safety of nanomaterials (NMs) and open new frontiers in biological fields by the use of NMs.
Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Hiromi
H
Nabeshi
Tomoaki
T
Yoshikawa
Keigo
K
Matsuyama
Yasutaro
Y
Nakazato
Akihiro
A
Arimori
Masaaki
M
Isobe
Saeko
S
Tochigi
Sayuri
S
Kondoh
Toshiro
T
Hirai
Takanori
T
Akase
Takuya
T
Yamashita
Kohei
K
Yamashita
Tokuyuki
T
Yoshida
Kazuya
K
Nagano
Yasuhiro
Y
Abe
Yasuo
Y
Yoshioka
Haruhiko
H
Kamada
Takayoshi
T
Imazawa
Norio
N
Itoh
Masuo
M
Kondoh
Kiyohito
K
Yagi
Tadanori
T
Mayumi
Shin-ichi
S
Tsunoda
Yasuo
Y
Tsutsumi
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D005174:Factor XII / Q000378:metabolism; D005260:Female; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity*; D010316:Particle Size; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis; D014914:Whole Blood Coagulation Time
D012822:Silicon Dioxide; D005174:Factor XII