Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Signalling Mediators to Attenuate Chemotherapy-induced Intestinal Disruptions
Monday, Feb. 16, 1-2 p.m.
CSF-1302
Hello Everyone,
You are warmly invited to attend the upcoming seminar on Monday, February 16th, 2026. Please find the details below.
February 16th, 2026
1:00 p.m. – 2:00 p.m.
CSF-1302
The direct link for the meeting is:
https://mun.webex.com/mun/j.php?MTID=mef6284c3c5998928921692f0269ab1fc
Speaker: Dr. Sarah Parsons (Ph.D. ,Postdoc Fellow, Dr. Cheema’s Lab)
Title: Effect of eicosapentaenoic acid and docosahexaenoic acid on signalling mediators to attenuate chemotherapy-induced intestinal disruptions (doctoral thesis research)
Abstract:
Background: Chemotherapy agents, irinotecan (CPT-11) and 5-fluorouracil (5-FU), treat advanced colorectal cancer, but cause chemotherapy-induced intestinal disruptions mediated in part by cytokines and oxylipins. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are known to alter cytokines and the balance of oxylipins in other inflammatory conditions. The present doctoral thesis investigated effects of dietary EPA and DHA on inflammatory mediators and intestinal microbiota composition.
Methods: Female Fischer 344 rats were fed a control diet or a diet containing fish oil initiated on the same day as chemotherapy (day 0). Ward colon tumor was implanted and allowed to grow for ~2 weeks prior to giving a clinically relevant dose of CPT-11 and 5-FU, administered sequentially within 24 hours. Rats were euthanized on day 0 and following chemotherapy on days 2, 4, and 8. Ileum and colon tissue were assessed for phospholipid fatty acid molecular species, cytokines, oxygenase enzyme proteins, and oxylipins. Fecal microbiota sequencing, histological colonic inflammatory scoring, and colonic myeloperoxidase levels were also assessed.
Results: Chemotherapy depleted total phospholipids and essential fatty acids in colonic phospholipid while having no effect on ileal phospholipid. Total and individual oxylipins derived from AA increased after chemotherapy treatment, including 5-hydroxyeicosatetraenoic acid (HETE), 11,12-DiHETE, prostaglandin (PG) D2, PGE2, 6-keto-PGF1α, and thromboxane (Tx) B2 in colon tissue and 6-keto-PGF1α, 8-HETE, and leukotriene B4 in ileum tissue. Early AA-derived signals corresponded with chemotherapy-induced disruptions to intestinal microbial communities and reduced total branched-chain fatty acids and isovalerate. Overt inflammation in the ileum and colon was undetected through cytokines, immunohistochemistry, and myeloperoxidase levels. Feeding the EPA+DHA diet resulted in a 15- and 2-fold enrichment from baseline to day 8 in EPA and DHA content of colonic membrane phospholipid (w/w%), respectively, and a 40-fold and 2-fold increase in EPA and DHA content in ileal membrane phospholipid (w/w%), respectively. Dietary EPA and DHA attenuated restoration of total AA by day 8 with lower AA content in colonic PC 16:0_20:4 and PI 20:4_18:0 than in animals fed the control diet. The EPA-DHA diet attenuated colonic TXB2 and PGE2 by day 2 and stabilized the change in total AA-derived oxylipins, PGD2, and PGE2 from baseline to day 8, bringing TXB2 below baseline post-chemotherapy. Ileal 6-keto-PGF1α and PGD2 also reduced by day 4 to levels below baseline while increasing the anti-inflammatory AA metabolite lipoxin A4. With EPA and DHA phospholipid enrichment, EPA- and DHA-derived oxylipins increased by day 8, many of which are precursors to several specialized pro-resolving lipid mediators. Reduced AA metabolites and increased EPA and DHA metabolites implicated a lower inflammatory milieu likely responsible for mitigating early depletion of differentiating taxa and the number of late differentiating taxa in response to chemotherapy.
Conclusion: This study suggests that the beneficial effect of EPA and DHA on ileum and colon tissue after cytotoxic chemotherapy is likely related to inhibition of regulatory processes and of oxygenase enzymes. Provision of EPA and DHA increased the very low levels of EPA and DHA content in ileal and colonic membrane phospholipid yielding EPA and DHA metabolites while reducing AA metabolites. Dietary EPA and DHA may provide an important adjunct therapy to lower the risk of adverse intestinal effects of chemotherapy in colorectal cancer patients
All are welcome to attend. Please mark your calendars and join us for this exciting presentation.
Presented by Department of Human Biosciences