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

Abstract

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)-α, 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 (AOC1) was a potential target of LD4-PDT. Novel photosensitizer agent LD4-PDT represents an efficient treatment method for UC, and AOC1 may be a promising target.

Photodynamic Therapy for Inflammatory and Cancerous Diseases of the Intestines: Molecular Mechanisms and Prospects for Application

“…Moreover, a recent study reported that LD4-PDT facilitated the healing of colonic mucosa, regulated gut microbiota, and ameliorated clinical symptoms of UC 19 . This study presents compelling evidence supporting the multifaceted effects of LD4-PDT, which include the regulation of inflammatory cytokine balance and modulation of gut microbiota composition.…”

“…PDT offers several advantages, including minimally invasive procedures, dual-targeted killing, minimal toxicity and side effects, and the potential for repeated treatments 1 . It fulfills the criteria for the aforementioned new treatment options for IBD 19 . Numerous studies have showcased the considerable advantages of PDT in treating inflammatory diseases, including IBD 4 , 36 , 37 .…”

“…This study presents compelling evidence supporting the multifaceted effects of LD4-PDT, which include the regulation of inflammatory cytokine balance and modulation of gut microbiota composition. These combined actions result in the restoration of the colonic proteome in TNBS-induced colitis rats, leading to the effective alleviation of acute colitis 19 . Mechanistically, the beneficial effects of LD4-PDT on colitis in rats may be attributed to its regulation of the AOC1 target 19 .…”

Extracellular vesicles as a novel photosensitive drug delivery system for enhanced photodynamic therapy

“…Since then, several PSs, such as 5-aminolevulinic acid (5-ALA) and temoporfin, have been approved for cancer therapy ( Fotinos et al, 2006 ). Notably, with the development of endoscopy and fiberoptic technologies, PSs (e.g., 5-ALA) have been applied to treat gastrointestinal diseases, such as ulcerative colitis ( Rong et al, 2021 ). In fact, Reinhard et al (2015) reported a liposomal formulation of meta-tetra (hydroxyphenyl) chlorin that alleviated colitis and prevented colitis-associated carcinogenesis in mice.…”

“…Photodynamic therapy (PDT), a non-invasive therapeutic approach employing light irradiation and photosensitizers (PSs) to remove unwanted cells, has been proven efficacious for the treatment of several diseases, including cancers ( Zheng et al, 2020 ; Zou et al, 2021 ), cardiovascular disease ( Kim et al, 2013 ), inflammatory bowel disease ( Rong et al, 2021 ), and diabetic ocular disease ( van Rijssen et al, 2021 ). Compared with traditional treatment methods such as surgery, radiotherapy, and chemotherapy, PDT exhibited efficient therapeutic action and low systemic toxicity ( Feng et al, 2020 ; Gunaydin et al, 2021 ).…”