Mo <sub>3</sub>Se <sub>4</sub> nanoparticle with ROS scavenging and multi-enzyme activity for the treatment of DSS-induced colitis in mice

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Abstract

Ulcerative colitis (UC), as a most common inflammatory bowel disease (IBD), has become a global public health concern. Exploring novel method of treating UC is urgent and necessary. Recently, nanozyme with excellent antioxidant properties may be one useful therapeutic strategy. In this study, a two-dimensional transition metal chalcogenide (TMCs) nano flake and polyethylene glycol (PEG) modified Mo ₃Se ₄ nano flakes (PMNFs) was synthesized, which had multi-enzyme activity, including peroxidase, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). The inhibition effect of PMNFs on sodium dextran sulfate (DSS)-induced colitis was explored. UC was effectively inhibited by PMNFs in this work. PMNFs significantly reduced disease activity index (DAI) score, including weight loss, colon shorten and histopathological abnormalities. The possible mechanism of PMNFs-attenuated colitis was investigated. The results showed that PMNFs reversed DSS-induced oxidative damage, and the antioxidant pathway Nrf2-keap1 signal was activated by PMNFs. Moreover, PMNFs suppressed the expression of pro-inflammatory factors including IL-1β, TNF-α, IFN-β and IL-6 via the inactivation of TLR4/NF-κB pathway in DSS-induced colitis and LPS-treated macrophage. Furthermore, PMNFs treatment prevented the reduction of tight junction proteins (ZO-1, occludin, and claudin-1) and mucin-2 (MUC-2) as well as the up-regulation of epithelial apoptosis caused by DSS. These findings demonstrate that the PMNFs against DSS-induced colitis due to its prevention on oxidative damage, inflammation, and intestine barrier breakdown. Thus, PMNFs have a potential application in the treatment of various oxidative stress or inflammation-related diseases.

Graphical abstract

Highlights

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Mo ₃Se ₄ nano flakes (PMNFs) can effective scavenge ROS in vivo and in vitro.
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PMNFs have multi-enzyme activity, including the peroxidase, GPx, SOD, and CAT.
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PMNFs can prevent symptoms of colitis induced by DSS in mice.
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PMNFs against DSS-induced colitis through prevention on oxidative damage, inflammation, and intestine barrier breakdown.

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Ulcerative colitis

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Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon. Ulcerative colitis usually presents with bloody diarrhoea and is diagnosed by colonoscopy and histological findings. The aim of management is to induce and then maintain remission, defined as resolution of symptoms and endoscopic healing. Treatments for ulcerative colitis include 5-aminosalicylic acid drugs, steroids, and immunosuppressants. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. The therapeutic armamentarium for ulcerative colitis is expanding, and the number of drugs with new targets will rapidly increase in coming years.

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Author and article information

Contributors

Xianxiang Wang

Journal

Journal ID (nlm-ta): Redox Biol

Journal ID (iso-abbrev): Redox Biol

Title: Redox Biology

Publisher: Elsevier

ISSN (Electronic): 2213-2317

Publication date PMC-release: 14 August 2022

Publication date Collection: October 2022

Publication date (Electronic): 14 August 2022

Volume: 56

Electronic Location Identifier: 102441

Affiliations

[a ]College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China

[b ]College of Science, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China

[c ]College of Agronomy, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China

[d ]State Key Laboratory of Hybrid Rice, Rice Research Institute, Sichuan Agricultural University, Chengdu, 611130, China

Author notes

[∗ ]Corresponding author. xianxiangwang@ 123456hotmail.com

[1]

These authors contributed equally to this work.

Article

Publisher Item ID: S2213-2317(22)00213-0 Publisher ID: 102441

DOI: 10.1016/j.redox.2022.102441

PMC ID: 9411672

PubMed ID: 35985164

SO-VID: 158d17cf-2f16-4118-b818-83c805422cec

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 16 June 2022

Date revision received : 6 August 2022

Date accepted : 11 August 2022

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