4.7 Article

Photodynamic Therapy of Novel Photosensitizer Ameliorates TNBS-Induced Ulcerative Colitis via Inhibition of AOC1

Journal

FRONTIERS IN PHARMACOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.746725

Keywords

ulcerative colitis; gut microbiota; photodynamic therapy; novel photosensitizer; AOC1

Funding

  1. national major science and technology special project for significant new drugs development [2018ZX09711001-005-018/2019ZX09721001-006001]
  2. medical and health science and technology innovation project [2017-I2M-3-021/2019-I2M-1-005]
  3. key technologies R&D program of Tianjin [20YFZCSY00570]

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Combining photodynamic therapy (PDT) with a novel photosensitizer LD4 for treating ulcerative colitis (UC) in rat models can improve survival rates, modulate expression of inflammatory factors, protect intestinal epithelial integrity, rebuild intestinal microflora balance, and reprogram protein expression profiles. AOC(1) emerges as a potential target in this efficient UC treatment approach using LD4-PDT.
Ulcerative colitis (UC), a chronic, nonspecific inflammatory bowel disease characterized by continuous and diffuse inflammatory changes in the colonic mucosa, requires novel treatment method. Photodynamic therapy (PDT), as a promising physico-chemical treatment method, were used to treat UC rats' model with novel photosensitizer LD4 in this paper, the treatment effect and mechanism was investigated. LD4-PDT could improve the survival rate of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC model rats, decrease expression of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-alpha, malondialdehyde (MDA), myeloperoxidase (MPO) and increase the expression of glutathione (GSH) and superoxide oxidase (SOD), while protecting the integrity of the intestinal epithelium. LD4-PDT treatment could rebuild the intestinal microflora composition and reprogram the colonic protein profiles in TNBS-induced rats to almost the normal state. Proteomics analysis based upon TNBS-induced UC model rats revealed that Amine oxidase copper-containing 1 (AOC(1)) was a potential target of LD4-PDT. Novel photosensitizer agent LD4-PDT represents an efficient treatment method for UC, and AOC(1) may be a promising target.

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