Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 14, Issue -, Pages 8361-8378Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S210655
Keywords
platinum nanoparticles; ulcerative colitis; gut-microbiota; anti-inflammation; gut-barrier function
Funding
- National Natural Science Foundation of China [31601406]
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Purpose: This study aimed to evaluate the anti-colitis potential of platinum nanoparticles (PtNPs). Materials and methods: 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. Results: 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-alpha, 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-a 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-kappa B signaling suppression. High-throughput 16S rRNA sequencing of fecal samples unveiled that PtNPs induced gut dysbiosis by unfavorably altering alpha-diversity, Firmicutes/Bacteroidetes ratio, and richness of certain specific bacteria. Conclusion: PtNPs are a promising anti-colitis agent, but may negatively impact gut-microbiota.
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