Tiwari Priyanka, Jena Gopabandhu
Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sahibzada Ajit Singh Nagar, Punjab, 160062, India.
Inflamm Res. 2025 Jul 31;74(1):107. doi: 10.1007/s00011-025-02072-x.
Dextran sulfate sodium (DSS)-induced colitis in rodents is considered a well-established experimental model for the induction of ulcerative colitis (UC) and its extra-intestinal manifestations (EIMs). The influence of strain on EIMs of UC remains poorly understood. The present study elucidated the strain-specific responses to different concentrations of DSS and its effects on the local (colon), systemic (DNA damage in peripheral blood), and extra-intestinal (liver, pancreas, brain) manifestations.
BALB/c and C57BL/6 mice, two commonly used rodent strains, were assigned to control and DSS (0.5%, 1%, 2%, and 3% w/v) treatment groups. DSS was provided in drinking water for 7 days over three cycles, with a 7-day inter-cycle remission. No other treatments or interventions were provided.
BALB/c exhibited gradual weight loss even at the lower doses of DSS, while C57BL/6 showed an early and sustained weight loss, particularly at the higher doses, contributing to greater severity and mortality. C57BL/6 exhibited significant systemic and colonic damage, with elevated inflammatory markers (nitrite, TNF-α, IL-1β, LPS) and reduced IL-10 in all the target organs. In contrast, MPO activity and goblet cell loss were more significant in BALB/c. C57BL/6 exhibited significant increase in the intestinal permeability as well as expression of TLR4 in colon and brain as compared to BALB/c mice. Overall, C57BL/6 mice showed significant increase in UC associated brain damage at higher concentrations of DSS, whereas BALB/c exhibited significant liver and pancreatic damage in a dose-dependent manner to DSS exposure. The expression of apoptotic cells and NF-κB/ICAM-1 increased dose-dependently in both the strains, with distinct patterns of expressions at the target organs.
Strain-specific differences in inflammation, cell adhesion, apoptosis, and systemic DNA damage may be responsible for the differential severity, susceptibility, and the extent of colonic and extra-colonic damage observed in BALB/c and C57BL/6 mice. These findings underscore the importance of selecting an appropriate experimental model for UC and can offer translational relevance in predicting organ susceptibility and managing the intestinal and extraintestinal complications.
硫酸葡聚糖钠（DSS）诱导的啮齿动物结肠炎被认为是一种成熟的溃疡性结肠炎（UC）及其肠外表现（EIMs）的实验模型。品系对UC肠外表现的影响仍知之甚少。本研究阐明了不同品系对不同浓度DSS的特异性反应及其对局部（结肠）、全身（外周血DNA损伤）和肠外（肝脏、胰腺、脑）表现的影响。
将两种常用的啮齿动物品系BALB/c和C57BL/6小鼠分为对照组和DSS（0.5%、1%、2%和3% w/v）处理组。在三个周期内，连续7天通过饮用水给予DSS，周期之间有7天的缓解期。未给予其他治疗或干预。
即使在较低剂量的DSS处理下，BALB/c小鼠也出现逐渐体重减轻，而C57BL/6小鼠则表现出早期且持续的体重减轻，尤其是在较高剂量时，导致更严重的病情和更高的死亡率。C57BL/6小鼠表现出显著的全身和结肠损伤，所有靶器官中的炎症标志物（亚硝酸盐、TNF-α、IL-1β、LPS）升高，IL-10降低。相比之下，BALB/c小鼠的髓过氧化物酶（MPO）活性和杯状细胞损失更为显著。与BALB/c小鼠相比，C57BL/6小鼠的肠道通透性以及结肠和脑中TLR4的表达显著增加。总体而言，在较高浓度的DSS处理下，C57BL/...
