Our observation of snPt1-induced cytotoxicity in cell culture suggests that snPt1 may be internalized by renal cells, with concomitant induction of ROS production or DNA damage. However,

alternative toxic effects (such as cytotoxicity of inflammatory cytokines on renal cells by accumulation of inflammatory cells in the kidney) might emerge during chronic exposure to snPt1. At equivalent dose levels, platinum particles of 8 nm in size did not induce apparent toxic effects in renal tissues by acute or chronic administration. This result suggests that selection of specific size ranges for the platinum particles might overcome the undesirable side effects. Current studies have shown that organic cation transporter 2 (OCT2) is highly expressed in kidney

and plays an important role in the nephrotoxicity of cisplatin [40, 41]. MG-132 clinical trial Identification of the snPt1 transporter may help to clarify the mechanism of snPt1-induced nephrotoxicity. Conclusions In the CBL-0137 order present study, we investigated the biological safety of platinum nanoparticles in mice and found that platinum particles of less than 1 nm induced kidney injury, although the injurious effects were reduced by increasing the nanoparticle size. For future nanoparticle applications, it will be critical GSK690693 to further understand the bioactivity and kinetics of materials less than 1 nm in size.

Accumulation of toxicity profiles will aid in the creation of the safe and efficacious nanomaterials and contribute to the advancement of the field. D-malate dehydrogenase Acknowledgements The authors thank all members of our laboratory for useful comments. This study was partly supported by a grant from the Ministry of Health, Labour, and Welfare of Japan. Electronic supplementary material Additional file 1: Figure S1: Cytotoxicity of snPt1 in renal cells. MDCK cells were treated with vehicle, snPt1, or snPt8 at 0, 10, 20, 40, or 60 μg/ml. After 24 h exposure, morphology of the cells was photographed. Higher magnification images are shown in the insets. (PPT 608 KB) Additional file 2: Figure S2: (A) Histological analysis of kidney tissues in intraperitoneally administered mice. Vehicle or test article (snPt1 or snPt8 at 10 mg/kg) was administered intraperitoneally to mice as a single dose. At 24 h after administration, kidneys were collected and fixed with 4% paraformaldehyde. Tissue sections were stained with hematoxylin and eosin and observed under a microscope. (B) Acute kidney injury score in mice treated intraperitoneally with vehicle, snPt1, or snPt8. Grade 0: none, 1: slight, 2: mild, 3: moderate, 4: severe. (PPT 202 KB) References 1.