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

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
	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-PGF1α	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
PGF2α	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.