Low-dose, subchronic exposure to silver nanoparticles causes mitochondrial alterations in Sprague–Dawley rats

Background/Aims: Our recent study indicated that the serum microcystin-LR (MC-LR) level is positively linked to the risk of human hepatocellular carcinoma (HCC). Gankyrin is over-expressed in cancers and mediates oncogenesis; however, whether MC-LR induces tumor formation and the role of gankyrin in this process is unclear. Methods: We induced malignant transformation of L02 liver cells via 35 passages with exposure to 1, 10, or 100 nM MC-LR. Wound healing, plate and soft agar colony counts, and nude mice tumor formation were used to evaluate the tumorigenic phenotype of MC-LR-treated cells. Silencing gankyrin was used to confirm its function. We established a 35-week MC-LR exposure rat model by twice weekly intraperitoneal injection with 10 μg/kg body weight. In addition, 96 HCC patients were tested for tumor tissue gankyrin expression and serum MC-LR levels. Results: Chronic low-dose MC-LR exposure increased proliferation, mobility, clone and tumor formation abilities of L02 cells as a result of gankyrin activation, while silencing gankyrin inhibited the carcinogenic phenotype of MC-LR-treated cells. MC-LR also induced neoplastic liver lesions in Sprague-Dawley rats due to up-regulated gankyrin. Furthermore, a trend of increased gankyrin was observed in humans exposed to MC-LR. Conclusion: These results suggest that MC-LR induces hepatocarcinogenesis in vitro and in vivo by increasing gankyrin levels, providing new insight into MC-LR carcinogenicity studies.

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Genotoxicity of Silver Nanoparticles in Lung Cells of Sprague Dawley Rats after 12 Weeks of Inhalation Exposure

Toxics ◽

10.3390/toxics1010036 ◽

2013 ◽

Vol 1 (1) ◽

pp. 36-45 ◽

Cited By ~ 10

Author(s):

Hyun Cho ◽

Jae Sung ◽

Kyung Song ◽

Jin Kim ◽

Jun Ji ◽

...

Keyword(s):

Silver Nanoparticles ◽

Inhalation Exposure ◽

Lung Cells ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Blood Biochemical and Hematological Study after Subacute Intravenous Injection of Gold and Silver Nanoparticles and Coadministered Gold and Silver Nanoparticles of Similar Sizes

BioMed Research International ◽

10.1155/2018/8460910 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Ji Hyun Lee ◽

Mary Gulumian ◽

Elaine M. Faustman ◽

Tomomi Workman ◽

KiSoo Jeon ◽

...

Keyword(s):

Silver Nanoparticles ◽

Low Dose ◽

Systemic Toxicity ◽

Blood Biochemistry ◽

Control Group ◽

High Dose ◽

Sprague Dawley ◽

Gold And Silver Nanoparticles ◽

Blood Biochemical ◽

Active Partial Thromboplastin Time

Background. To investigate the effect of subacute intravenous administration AgNP (silver nanoparticles, 10 nm) and AuNP (gold nanoparticles, 12.8 nm) and AgNP/AuNP mixture to blood biochemistry, hematology, and platelet coagulation, subacute toxicity study was conducted. Methods. AuNP and AgNP in which their size distribution was not statistically different, mixed or separate, were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The rats were allowed to recover for a further 4 weeks in order to examine systemic toxicity expressed in the blood biochemistry and hematology. The dose groups (5 males per group for the administration and 3 males for the recovery) consisted of 7 divisions, i.e., control, AgNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), AuNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), and mixed AgNP/AuNP (with a low dose of 10/10 μg/kg/day and a high dose of 100/100 μg/kg/day). Results. There were no significant dose-related changes in the hematology and blood biochemical values for the rats. Coagulation time in terms of the active partial thromboplastin time (APTT) and prothrombin time (PT) did not show any significant changes, when compared to the control group. Conclusion. The subacute injection of AuNP and AgNP or their mixture did not induce any noticeable systemic toxicity.

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