TY - JOUR

T1 - Assessing acute colitis induced by dextran sulfate sodium in rats and its impact on gastrointestinal fluids

AU - Klitgaard, Mette

AU - Kristensen, Maja Nørgaard

AU - Venkatasubramanian, Ramakrishnan

AU - Guerra, Priscila

AU - Jacobsen, Jette

AU - Berthelsen, Ragna

AU - Rades, Thomas

AU - Müllertz, Anette

N1 - Funding Information: 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).

PY - 2023

Y1 - 2023

N2 - 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. Graphical Abstract: [Figure not available: see fulltext.]

AB - 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. Graphical Abstract: [Figure not available: see fulltext.]

KW - Bile salts

KW - Charged aerosol detection

KW - DSS-induced colitis

KW - Lipids

KW - Luminal pH

U2 - 10.1007/s13346-023-01313-y

DO - 10.1007/s13346-023-01313-y

M3 - Journal article

C2 - 36913104

AN - SCOPUS:85149907341

VL - 13

SP - 1484

EP - 1499

JO - Drug Delivery and Translational Research

JF - Drug Delivery and Translational Research

SN - 2190-393X

ER -