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Assessing acute colitis induced by dextran sulfate sodium in rats and its impact on gastrointestinal fluids

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Abstract

Dextran sulfate sodium (DSS) is commonly used to induce colitis in rats. While the DSS-induced colitis rat model can be used to test new oral drug formulations for the treatment of inflammatory bowel disease, the effect of the DSS treatment on the gastrointestinal tract has not been thoroughly characterized. Additionally, the use of different markers to assess and confirm successful induction of colitis is somewhat inconsistent. This study aimed to investigate the DSS model to improve the preclinical evaluation of new oral drug formulations. The induction of colitis was evaluated based on the disease activity index (DAI) score, colon length, histological tissue evaluation, spleen weight, plasma C-reactive protein, and plasma lipocalin-2. Furthermore, the study investigated how the DSS-induced colitis affected the luminal pH, lipase activity, and concentrations of bile salts, polar lipids, and neutral lipids. For all evaluated parameters, healthy rats were used as a reference. The DAI score, colon length, and histological evaluation of the colon were effective disease indicators in DSS-induced colitis rats, while spleen weight, plasma C-reactive protein, and plasma lipocalin-2 were not. The luminal pH of the colon and bile salt- and neutral lipid concentrations in regions of the small intestine were lower in DSS-induced rats compared to healthy rats. Overall, the colitis model was deemed relevant for investigating ulcerative colitis-specific formulations.

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Abbreviations

CD:

Crohn’s disease

CRP:

C-reactive protein

DAI:

Disease activity index

DSS:

Dextran sulfate sodium

DSS rats:

Dextran sulfate sodium-induced colitis rats

GI:

Gastrointestinal

HEP:

Humane endpoint

IBD:

Inflammatory bowel disease

RP-HPLC-CAD:

Reversed-phase high-performance liquid chromatography-charged aerosol detection

UC:

Ulcerative colitis

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Funding

The research is funded by the Danish National Research Foundation (DNRF122), Villum Fonden (Grant No. 9301), Center for intelligent drug delivery and sensing using microcontainers and nanomechanics (IDUN), and Lundbeckfonden (R286-2018–2015).

Author information

Authors and Affiliations

  1. Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Mette Klitgaard, Maja Nørgaard Kristensen, Ramakrishnan Venkatasubramanian, Jette Jacobsen, Ragna Berthelsen, Thomas Rades & Anette Müllertz

  2. The Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Health Technology, Technical University of Denmark, 2800, Kongens Lyngby, Denmark

    Maja Nørgaard Kristensen

  3. Department of Veterinary and Animal Science, University of Copenhagen, Stigbøjlen 4, 1870, Frederiksberg C, Denmark

    Priscila Guerra

  4. Bioneer:FARMA, Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Anette Müllertz

Authors
  1. Mette Klitgaard
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  2. Maja Nørgaard Kristensen
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  3. Ramakrishnan Venkatasubramanian
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  4. Priscila Guerra
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  5. Jette Jacobsen
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  6. Ragna Berthelsen
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  7. Thomas Rades
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  8. Anette Müllertz
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Contributions

MK conceptualization, investigation, methodology, writing – original draft. MNK conceptualization, investigation, methodology, writing – original draft. RV investigation, methodology, writing—review & editing. PG investigation, methodology, writing—review & editing. JJ methodology, writing—review & editing, supervision, project administration. RB methodology, writing—review & editing, supervision, project administration. TR methodology, writing—review & editing, supervision, project administration. AM methodology, project administration, resources, funding acquisition, writing—review & editing, supervision.

Corresponding author

Correspondence to Anette Müllertz.

Ethics declarations

Ethics approval

All animal studies were performed at the University of Copenhagen under license number 2019–15-0201–00262. All procedures complied with the Danish laws regarding animal experiments, the EU Directive 2010/63/EU, and the ARRIVE guidelines.

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Not applicable.

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Not applicable.

Competing interests

The authors declare no competing interests.

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Mette Klitgaard and Maja Nørgaard Kristensen contributed equally to this work.

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Supplementary file1 (DOCX 468 KB)

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Klitgaard, M., Kristensen, M.N., Venkatasubramanian, R. et al. Assessing acute colitis induced by dextran sulfate sodium in rats and its impact on gastrointestinal fluids. Drug Deliv. and Transl. Res. 13, 1484–1499 (2023). https://doi.org/10.1007/s13346-023-01313-y

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