Dietary eicosapentaenoic and docosahexaenoic acids decrease prostanoids in the ileum of rats treated with irinotecan and 5-fluorouracil

doi:10.4251/wjgo.120472

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World Journal of Gastrointestinal Oncology

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1948-5204

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Sep 15, 2026; 18(9): 120472
Published online Sep 15, 2026. doi: 10.4251/wjgo.120472

Table 1 Total phospholipid fatty acids in ileum tissue of rats treated with chemotherapy and fed eicosapentaenoic acid + docosahexaenoic acid diet, mean ± SEM

Phospholipid fatty acids (% w/w)	Baseline	Control diet			EPA + DHA diet			Main effects		Interaction
Phospholipid fatty acids (% w/w)	Day 0 (n = 5)	Day 2 (n = 4)	Day 4 (n = 4)	Day 8 (n = 4)	Day 2 (n = 5)	Day 4 (n = 4)	Day 8 (n = 4)	P value (diet)	P value (day)	P value (diet and day)
18: 2n-6	3.9 ± 0.38	3.8 ± 0.16³	5.3 ± 0.17	4.0 ± 0.19	3.9 ± 0.31	5.0 ± 0.17	4.4 ± 0.22		0.0003
20: 4n-6	9.7 ± 0.28	11 ± 0.25¹^,³	8.9 ± 0.47	10 ± 0.16	10 ± 0.13³	8.0 ± 0.30	8.6 ± 0.33²	0.001	< 0.001	0.031
Total n-6	14 ± 0.39	15 ± 0.16	14 ± 0.17	14 ± 0.20	14 ± 0.33	13 ± 0.20	13 ± 0.24	0.049	0.003
18: 3n-3	0.024 ± 0.009	0.002 ± Tr³	0.053 ± Tr	0.050 ± 0.011	0.027 ± 0.020³	0.057 ± 0.005	0.058 ± 0.014		0.002
20: 5n-3	Tr	0	0.002 ± 0.001	Tr	0.058 ± 0.035³	0.54 ± 0.10²	0.80 ± 0.12²	< 0.001	< 0.001	< 0.001
22: 6n-3	0.29 ± 0.01	0.27 ± 0.005	0.31 ± 0.003	0.30 ± 0.02	0.31 ± 0.014³	0.52 ± 0.03²	0.69 ± 0.02²	< 0.001	< 0.001	< 0.001
Total n-3	0.31 ± 0.018	0.27 ± 0.005	0.37 ± 0.005	0.36 ± 0.027	0.40 ± 0.069³	1.1 ± 0.14²	1.5 ± 0.15²	< 0.001	< 0.001	< 0.001

¹Denotes significant differences between baseline and day 2 in rats fed the control diet (chemotherapy effect).

²Denotes significant differences between diets on the same day (diet effect).

³Denotes significant differences between days within the same diet (time effect).

Tr: Trace; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid.

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Table 2 Oxylipins derived from n-6 polyunsaturated fatty acid in ileum tissue of rats treated with chemotherapy and fed eicosapentaenoic acid + docosahexaenoic acid diet, mean ± SEM

Oxylipin (ng/mg of protein)	Baseline	Control diet			EPA + DHA diet			Main effects		Interaction
Oxylipin (ng/mg of protein)	Day 0 (n = 5)	Day 2 (n = 4)	Day 4 (n = 4)	Day 8 (n = 4)	Day 2 (n = 5)	Day 4 (n = 4)	Day 8 (n = 4)	P value (diet)	P value (day)	P-diet × day
PGD₂	88 ± 5.8	110 ± 16⁶	66 ± 8.8	83 ± 7.9	92 ± 4.1⁶	31 ± 6.0	36 ± 2.3⁵	< 0.001	< 0.001	0.026
PGE₂	10 ± 0.48	22 ± 1.1	20 ± 2.5	11 ± 1.7	25 ± 3.7	16 ± 9.7	5.9 ± 0.42		< 0.001
6-keto-PGF_1α	19 ± 0.93	34 ± 3.1⁴^,⁶	19 ± 1.8	19 ± 1.5	32 ± 3.0⁶	9.4 ± 1.5⁵	9.2 ± 0.46⁵	< 0.001	< 0.001	0.021
PGF_2α	63 ± 2.3	89 ± 12	49 ± 8.5	58 ± 2.7	79 ± 19⁶	21 ± 4.7	20 ± 2.3	0.007	< 0.001
¹TXB₂	170 ± 10	180 ± 27	110 ± 18	170 ± 18	150 ± 27⁶	60 ± 12	97 ± 15	0.006	< 0.001
5-HETE	37 ± 6.6	65 ± 5.3⁶	15 ± 3.6	50 ± 5.5	66 ± 9.8⁶	15 ± 5.1	48 ± 11		< 0.001
8-HETE	17 ± 3.3	49 ± 16⁴^,⁶	9.3 ± 2.4	26 ± 1.4	44 ± 8.1⁶	8.8 ± 2.4	23 ± 3.6		< 0.001
11-HETE	590 ± 97	1300 ± 408⁶	380 ± 112	750 ± 101	1000 ± 155	370 ± 107	630 ± 52		< 0.001
12-HETE	34 ± 6.3	56 ± 15⁶	21 ± 3.1	36 ± 6.3	37 ± 8.5	10 ± 2.3	29 ± 5.5		0.004
15-HETE	300 ± 32	330 ± 56⁶	150 ± 26	340 ± 12	380 ± 65⁶	120 ± 39	220 ± 37		< 0.001
20-HETE	1.5 ± 0.52	2.7 ± 1.2	0.91 ± 0.77	1.9 ± 0.21	1.2 ± 0.33	0.16 ± 0.16	1.0 ± 0.49
LTB₄	0.30 ± 0.045	0.92 ± 0.12⁴	0.35 ± 0.086	0.31 ± 0.06	0.83 ± 0.19⁶	0.09 ± 0.05	0.56 ± 0.34		< 0.001
LXA₄	0.16 ± 0.049	0.36 ± 0.13	0.033 ± Tr	0.11 ± 0.02	0.49 ± 0.12⁶	0.10 ± 0.02	0.57 ± 0.22⁵	0.024	0.004
²Sum of AA-derived	1400 ± 120	2400 ± 450⁴^,⁶	880 ± 170	1700 ± 140	2100 ± 190⁶	700 ± 180	1300 ± 50		< 0.001
³Sum of LA-derived	890 ± 160	1600 ± 240⁵^,⁶	1800 ± 390	690 ± 88	1500 ± 240⁶	690 ± 100⁵	830 ± 190		0.006	0.038
Sum n-6-derived	2300 ± 220	4000 ± 660⁴	2700 ± 250	2400 ± 200	3500 ± 250⁶	1400 ± 250	2100 ± 230	0.03	< 0.001

¹Thromboxane (TX) B₂ is the inactive but stable product of the bioactive precursor TXA₂.

²Sum of arachidonic acid-derived: Prostaglandin (PG) D₂, PGE₂, 6-keto-PGF_1α, PGF_2α, thromboxane (TX) B₂, 5-hydroxyeicosatetraenoic acid (HETE), 8-HETE, 11-HETE, 12-HETE, 15-HETE, 8,9-dihydroxy-eicosatetraenoic acid (DiHETE), 11,12-DiHETE, 14,15-DiHETE, 20-HETE (trace, not shown), leukotriene-B_4, and LXA₂.

³Sum of linoleic acid-derived: 9-hydroxyoctadecadienoic acid (HODE), 13-HODE, 9,10-dihydroxyoctadecenoic acid (DiHOME), 12,13-DiHOME. Two sample assessed for 13-HODE were more than three standard deviations from the aggregated mean of rats fed the eicosapentaenoic acid + docosahexaenoic acid diet. Thus, the two outliers were replaced with the mean of each outlier’s treatment group.

⁴Denotes significant differences between baseline and day 2 in rats fed the control diet (chemotherapy effect).

⁵Denotes significant differences between diets on the same day (diet effect).

⁶Denotes significant differences between days within the same diet (time effect).

Tr: Trace; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; PG: Prostaglandin; TX: Thromboxane; HETE: Hydroxyeicosatetraenoic acid; LT: Leukotriene; LX: Lipoxin; AA: Arachidonic acid; LA: Linoleic acid.

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Table 3 Oxylipins derived from n-3 polyunsaturated fatty acid in ileum tissue of rats treated with chemotherapy and fed eicosapentaenoic acid + docosahexaenoic acid diet, mean ± SEM

Oxylipin (ng/mg of protein)	Baseline	Control diet			EPA + DHA diet			Main effects		Interaction
Oxylipin (ng/mg of protein)	Day 0 (n = 5)	Day 2 (n = 4)	Day 4 (n = 4)	Day 8 (n = 4)	Day 2 (n = 5)	Day 4 (n = 4)	Day 8 (n = 4)	P value (diet)	P value (day)	P-diet × day
15-HEPE	7.7 ± 2.3	12 ± 1.3	2.9 ± 2.2	6.1 ± 1.3	13 ± 4.0⁵	11 ± 2.4	29 ± 5.8⁴	0.001	0.009	0.003
18-HEPE	1.1 ± 0.8	1.1 ± 1.1	Tr ± Tr	2.2 ± 1.3	5.0 ± 1.7⁵	6.8 ± 1.8	64 ± 17⁴	< 0.001	< 0.001	< 0.001
17,18-DiHETE	0.0 ± Tr	Tr ± Tr	0.06 ± 0.06	0.07 ± Tr	0.16 ± 0.06⁵	0.43 ± 0.16⁴	2.1 ± 0.19⁴	< 0.001	< 0.001	< 0.001
¹Sum EPA-derived	8.8 ± 3.0	13 ± 2.2	2.9 ± 2.2	8.4 ± 0.61	18 ± 5.0⁵	18 ± 4.0	94 ± 20⁴	< 0.001	< 0.001	< 0.001
4-HDoHE	3.9 ± 1.0	7.9 ± 1.3	2.1 ± 0.53	3.5 ± 0.43	9.2 ± 2.0⁵	2.5 ± 0.67	11 ± 3.1	0.037	< 0.001
8-HDoHE	0.4 ± 0.1	1.1 ± 0.41	0.06 ± 0.06	0.2 ± 0.07	0.81 ± 0.31	0.68 ± 0.17	1.2 ± 0.14
13-HDoHE	4.0 ± 0.3	3.5 ± 1.0	2.8 ± 0.98	3.3 ± 0.52	5.7 ± 1.4	3.5 ± 0.96	7.4 ± 1.9	0.023
14-HDoHE	4.3 ± 0.8	4.2 ± 1.2	2.7 ± 0.50	3.7 ± 0.70	5.8 ± 1.4	2.7 ± 0.34	5.4 ± 1.7
16-HDoHE	154 ± 20	170 ± 32	66 ± 18	160 ± 8.3	240 ± 56⁵	120 ± 34	340 ± 76⁴	0.013	0.005
17-HDoHE	4.2 ± 0.3	5.7 ± 1.2	5.0 ± 1.0	3.8 ± 0.67	8.4 ± 1.0	10 ± 6.8	10 ± 1.5	0.044
20-HDoHE	24 ± 7.9	41 ± 9.2	12 ± 7.5	31 ± 2.7	33 ± 7.7⁵	12 ± 2.7	58 ± 17		0.006
Protectin D1	0.71 ± 0.0	2.0 ± 0.40³^,⁴	0.54 ± 0.29	0.71 ± 0.11	1.8 ± 0.46⁵	0.61 ± 0.22	1.6 ± 0.49		< 0.001
²Sum DHA-derived	196 ± 26	230 ± 39	91 ± 20	210 ± 8.1	300 ± 68⁵	150 ± 38	430 ± 87	0.013	0.002
Sum n-3-derived	205 ± 28	250 ± 38	94 ± 20	220 ± 8.5	320 ± 72⁵	170 ± 42	520 ± 80⁴	0.002	< 0.001	0.018

¹Sum of eicosapentaenoic acid-derived oxylipins: 15-hydroxyeicosapentaenoic acid (HEPE), 18-HEPE, 17,18-dihydroxy-eicosatetraenoic acid (trace, not shown).

²Sum of docosahexaenoic acid-derived oxylipins: 4-hydroxy-docosahexaenoic acid (HDoHE), 8-HDoHE, 13-HDoHE, 14-HDoHE, 16-HDoHE, 17-HDoHE, 20-HDoHE, protectin-D1 (trace, not shown).

³Denotes significant differences between baseline and day 2 in rats fed the control diet (chemotherapy effect).

⁴Denotes significant differences between diets on the same day (diet effect).

⁵Denotes significant differences between days within the same diet (time effect).

Tr: Trace; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; HEPE: Hydroxyeicosapentaenoic acid; DiHETE: Dihydroxy-eicosatetraenoic acid; HDoHE: Hydroxy-docosahexaenoic acid.

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Table 4 Cytokines and chemokine in ileum tissue of rats treated with chemotherapy and fed eicosapentaenoic acid + docosahexaenoic acid diet, mean ± SEM

Immune signals (pg/mg of protein)	Baseline	Control diet			EPA + DHA diet			Main effects		Interaction
Immune signals (pg/mg of protein)	Day 0 (n = 5)	Day 2 (n = 4)	Day 4 (n = 4)	Day 8 (n = 4)	Day 2 (n = 5)	Day 4 (n = 4)	Day 8 (n = 4)	P value (diet)	P value (day)	P-diet × day
TNF-α	74 ± 2.4	58 ± 6.6¹	60 ± 6.6	93 ± 1.6	62 ± 7.1¹	69 ± 2.8	100 ± 6.9		< 0.001
IL-10	88 ± 3.0	67 ± 3.6	74 ± 15	110 ± 18	77 ± 8.6	87 ± 10	110 ± 21
Fractalkine	710 ± 31	600 ± 31¹	930 ± 120	890 ± 76	610 ± 50¹	946 ± 68	860 ± 79		< 0.001
IL-1β	220 ± 28	110 ± 15¹	140 ± 22	300 ± 35	140 ± 30¹	146 ± 23	330 ± 69		< 0.001
IL-6	480 ± 7.6	480 ± 9.8	490 ± 3.7	500 ± 9.5	500 ± 5.7	490 ± 6.7	520 ± 9.4

¹Denotes significant differences between days on the same diet (time effect).

EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; IL: Interleukin; TNF: Tumor necrosis factor.

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Citation: Parsons SR, Rivas-Serna IM, Clandinin MT, Mazurak VC. Dietary eicosapentaenoic and docosahexaenoic acids decrease prostanoids in the ileum of rats treated with irinotecan and 5-fluorouracil. World J Gastrointest Oncol 2026; 18(9): 120472
URL: https://www.wjgnet.com/1948-5204/full/v18/i9/120472.htm
DOI: https://dx.doi.org/10.4251/wjgo.120472

Parsons SR, Rivas-Serna IM, Clandinin MT, Mazurak VC. Dietary eicosapentaenoic and docosahexaenoic acids decrease prostanoids in the ileum of rats treated with irinotecan and 5-fluorouracil. World J Gastrointest Oncol 2026; 18(9): 120472 [DOI: 10.4251/wjgo.120472]

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