Date of Graduation

8-2023

Document Type

Thesis

Degree Name

Master of Science in Human Environmental Science (MS)

Degree Level

Graduate

Department

General Human Environmental Sciences

Advisor/Mentor

Trudo, Sabrina P.

Committee Member

Bailey, Mechelle T.

Second Committee Member

Zhao, Jiangchao

Keywords

Animal model; Apiaceous vegetables; Colorectal cancer; DSS induced colitis

Abstract

Colorectal cancer is the second leading cause of cancer-related deaths in the US. Dietary habits account for 50% of the cases. A westernized diet (high fat, high sugar/fructose, and low in fruits and vegetables) and inflammatory bowel diseases are risk factors for colorectal cancer. Evidence suggests phytochemicals in apiaceous vegetables (API; celery family) possess anti-inflammatory and potentially chemopreventive properties. Hence, investigation of whether the consumption of API mitigates acute colitis is warranted. Using mice fed the Total Western Diet (TWD) and administered dextran sodium sulfate (DSS; induces colitis), the objectives of this project are to identify the effects of API intake on 1) severity of colitis assessed by disease activity index (DAI), 2) protection of the gastrointestinal barrier against the effects of DSS, 3) colon biomarkers of inflammation and barrier function, and 4) serum inflammation markers. The TWD is formulated to mimic the average diet composition in the US, thus enhancing translation to humans. Hence, C57BL/6J mice (n=90) were divided into the following groups 1) TWD; 2) TWD+21% API wet wt:wt (10.5% celery + 10.5% parsnip; equivalent to a total of ~1 c/d in the human diet using allometric scaling based on kcals); 3) TWD+42% API (21% celery + 21% parsnip); 4) TWD+2% DSS; 5) TWD+21%API+DSS; 6) TWD+42%API+DSS. Mice were fed for 19 days with access to normal drinking water unless assigned to DSS on days 12-17. On day 20, mice were euthanized, and tissues were collected. Results showed that API supplementation mitigated weight loss caused by DSS but did not fully restore weight gain. DSS exposure led to colon shortening, while API supplementation minimized this effect. API also improved the weight/length ratio of the colon, indicating a reduction in colonic inflammation. The histological assessment confirmed the protective effects of API against colitis-induced damage. Notably, occludin expression, an important protein in tight junction formation, was decreased by DSS, but API supplementation had differential effects. NF-κB signaling, a key pathway in inflammation, was modulated by API supplementation. API reduced the expression of p-p65, a marker of inflammation, in the colon. However, this reduction was reversed in the groups receiving API and DSS, indicating an interaction between API and DSS-induced colitis. Serum cytokine analysis revealed that API supplementation decreased pro-inflammatory cytokines such as CXCL1, CXCL9, CXCL13, and G-CSF while increasing anti-inflammatory proteins like IL-4, IL-13, and IL-27. API intake showed beneficial effects on cell expression, histological parameters, and inflammatory markers in the DSS-induced colitis model. The results support the hypothesis that API intake reduces colitis severity and possesses anti-inflammatory properties. These findings align with previous studies using different models, providing important comparisons. API intake also protected the gastrointestinal barrier and reduced inflammatory cell infiltration. In conclusion, API supplementation demonstrates protective effects against DSS-induced colitis, modulates NF-κB signaling and inflammatory cytokines, and maintains gut barrier integrity. These findings highlight the potential of API as a dietary intervention to reduce colitis severity and mitigate CRC risk.

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