Platinum Nanoparticles As A Therapeutic Agent Against Dextran Sodium Sulfate-Induced Colitis In Mice

• Published in: International journal of nanomedicine Vol. 14; pp. 8361 - 8378
• Main Authors: Zhu, Suqin, Zeng, Mingyong, Feng, Guangxin, Wu, Haohao
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.10.2019; Dove; Dove Medical Press
• Subjects: Acute Disease; Administration, Oral; Animals; anti-inflammation; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Bacteria; Biodiversity; Body weight; Colitis; Colitis - chemically induced; Colitis - microbiology; Colitis - therapy; Colon - microbiology; Colon - pathology; Dextran Sulfate; Dextrans; Disease Models, Animal; EDTA; Gastrointestinal Microbiome - drug effects; gut barrier function; gut microbiota; Health aspects; Histochemistry; House mouse; Inflammation; Inflammation - pathology; Interleukins; Lipopolysaccharides; Macrophages; Male; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - therapeutic use; Metal Nanoparticles - ultrastructure; Mice; Mice, Inbred C57BL; Microbiota (Symbiotic organisms); Mitogens; Nanoparticles; Necrosis; Nitric oxide; Nitrogen oxides; Original Research; Platinum - therapeutic use; platinum nanoparticles; Polysaccharides; Proteins; RAW 264.7 Cells; RNA; Signal Transduction - drug effects; Sulfates; Tumor necrosis factor; Tumors; Ulcerative colitis; Canada; Japan; China; platinum nanoparticles; anti-inflammation; gut-barrier function; gut-microbiota; ulcerative colitis
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/ijn.s210655

This study aimed to evaluate the anti-colitis potential of platinum nanoparticles (PtNPs). 5-, 30- and 70-nm PtNPs were administered to C57BL/6 mice once daily by intragastric gavage for 8 d during and after 5-d dextran sodium sulfate treatment. According to body weight change, stool blood and consistency, and colon length and histopathology, PtNPs size-dependently alleviated DSS-induced murine colitis. PtNPs enhanced gut-barrier function by upregulating the colonic expressions of heat-shock protein 25 and tight junction proteins. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of white blood cells, PtNPs attenuated colonic and systemic inflammation. By suppressing lipopolysaccharide-triggered production of proinflammatory mediators, including nitric oxide, tumor necrosis factor-α and interleukin-6, PtNPs exerted direct anti-inflammatory activities in RAW264.7 macrophages through a mechanism involving intracellular reactive oxygen species scavenging and Toll-like receptor 4/NF-κB signaling suppression. High-throughput 16S rRNA sequencing of fecal samples unveiled that PtNPs induced gut dysbiosis by unfavorably altering α-diversity, Firmicutes/Bacteroidetes ratio, and richness of certain specific bacteria. PtNPs are a promising anti-colitis agent, but may negatively impact gut-microbiota.