Bioavailability and toxicokinetics of citrate-coated silver nanoparticles in rats.

Bioavailability, tissue distribution, blood concentration, and excretion of citrate-coated silver nanoparticles (AgNPs; size, 7.9 ± 0.95 nm by TEM diameter) were investigated. Male SD rats were treated by a single oral or intravenous administration of either 1 or 10 mg/kg AgNPs. Silver concentration of blood was determined at 10 min, and at 1, 2, 4, 8, 24, 48, and 96 h after treatment. Silver in the liver, lungs, and kidneys was also measured at 24 and 96 h after treatment. Excretion of silver nanoparticles via feces and urine was determined at 24 h after treatment. After oral administration, most AgNPs were found in feces, and their blood concentration was very low. This suggests that absorption through the gastrointestinal tract was not good. However, a high level of silver in the blood was detected after tail vein injection. When rats were injected with 1 mg/kg AgNPs, the silver concentration of blood was significantly elevated at 10 min after injection; the level subsequently decreased. In the rats treated with 10 mg/kg AgNPs, the elevated level did not decrease, but was maintained during the experimental period. On the basis of the values of AUC(oral)/AUC(iv), the bioavailability of orally administered AgNPs was 1.2% in the group treated with 1 mg/kg AgNPs and 4.2% in the group treated with 10 mg/kg AgNPs. AgNPs accumulated in the liver, lungs, and kidneys; the accumulated AgNPs were released into the blood stream. AgNP levels in the urine were extremely low compared to the levels in the feces. When rats were injected with AgNPs, these particles were also detected in feces at 24 h after treatment, which suggests bile secretion of AgNPs.

Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticles.

Toxicity of nanoparticles depends on many factors including size, shape, chemical composition, surface area, surface charge, and others. In this study, we compared the toxicity of different sized-silver nanoparticles (AgNPs) which are being widely used in consumer products due to its unique antimicrobial activity. When mice were treated with AgNPs 1mg/kg for 14 days by oral administration, small-sized AgNPs (22nm, 42nm, and 71nm) were distributed to the organs including brain, lung, liver, kidney, and testis while large-sized AgNPs (323nm) were not detected in those tissues. The levels of TGF-ß in serum were also significantly increased in the treated group of small-sized AgNPs but not in large-sized AgNPs. In addition, B cell distribution was increased in small-sized AgNPs but not in large-sized-AgNPs by the phenotype analysis. However, body weight or in the ratio of organ/body weight were not different between the control group and all the AgNPs-treated groups. The repeated-dose toxicity of AgNPs (42nm) was also investigated in mice by oral administration for 28 days. By the administration of AgNPs (0.25mg/kg, 0.50mg/kg, 1.00mg/kg), adverse impacts on liver and kidney were observed in a high dose-treated group (1.00mg/kg), when determined by blood chemistry and histipathological analysis. Cytokines including IL-1, IL-6, IL-4, IL-10, IL-12, and TGF-ß were also increased in a dose-dependent manner by repeated oral administration. In addition, B cell distribution in lymphocyte and IgE production were increased. Based on these results, it is suggested that repeated oral administration of nano-sized AgNPs may cause organ toxicity and inflammatory responses in mice.

Embryotropic effect of insulin-like growth factor (IGF)-I and its receptor on development of porcine preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer.

Insulin-like growth factor (IGF)-I is a receptor-mediated autocrine/paracrine growth/survival factor for mammalian embryo development. The present study investigated the temporal expression and regulation of porcine IGF-I receptor (IGF-IR) mRNA and the role of IGF-I on development of porcine in vitro fertilized (IVF) and somatic cell nuclear transfer (SCNT) embryos. As assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), the level of IGF-IR mRNA expression was high in unfertilized oocytes, 2-cell and 4-cell embryos and gradually decreased in 8-cell embryos, morulae, and blastocysts in both IVF and SCNT series. The IVF or SCNT embryos were cultured with 0, 1, 10, 50, or 100 ng/ml IGF-I for 168 hr. Supplementing with 50 ng/ml IGF-I increased blastocyst formation and the number of cells in inner cell masses (ICMs) in both IVF and SCNT embryos. In a second experiment, more blastocysts were obtained when IVF or SCNT embryos were cultured for the first 48 hr or for the entire 168 hr with 50 ng/ml IGF-I compared to culturing without IGF-I for 48 hr or with IGF-I for the last 120 hr or without IGF-I for the entire 168 hr. Treating IVF or SCNT embryos with 50 ng/ml IGF-I significantly up-regulated IGF-IR mRNA compared to untreated control embryos. In conclusion, the present study demonstrated that IGF-IR mRNA is expressed in porcine IVF and SCNT embryos, and that IGF-I improved the developmental competence of IVF and SCNT embryos through its specific receptors.

Seroprevalence of antibodies to Neospora caninum in dogs and raccoon dogs in Korea.

Neospora caninum is an important cause of abortion in cattle, and dogs are its only known definitive host. Its seroprevalence among domestic urban and rural dogs and feral raccoon dogs (Nyctereutes procyonoides koreensis) in Korea was studied by indirect fluorescent antibody test (IFAT) and by the neospora agglutination test (NAT), respectively. Antibodies to N. caninum were found in 8.3% of urban dogs and in 21.6% of dogs at dairy farms. Antibody titers ranged from 1:50 to 1:400. Antibodies to N. caninum were found in six (23%) of 26 raccoon dogs. However, the potential role of raccoon dogs as a source of horizontal transmission of bovine neosporosis needs further investigation. The results of this study suggest that there is a close relationship between N. caninum infection among dairy farm dogs and cattle in Korea. This study reports for the first time upon the seroprevalence of N. caninum infection in raccoon dogs in Korea.