#METABOLOMICS WORKBENCH michaelsa93_20170809_135138 DATATRACK_ID:1197 STUDY_ID:ST000846 ANALYSIS_ID:AN001369 PROJECT_ID:PR000600
VERSION             	1
CREATED_ON             	August 10, 2017, 2:57 pm
#PROJECT
PR:PROJECT_TITLE                 	Statin Immuno-Metabolomics in Asthma
PR:PROJECT_SUMMARY               	Innovative and novel therapies are urgently needed for the treatment of patients
PR:PROJECT_SUMMARY               	with severe asthma, especially those who are refractory to standard-of-care
PR:PROJECT_SUMMARY               	bronchodilators and inhaled corticosteroids. The Zeki lab is investigating the
PR:PROJECT_SUMMARY               	role of the mevalonate (MA) pathway, in the pathogenesis of airway inflammation
PR:PROJECT_SUMMARY               	and remodeling. Although statins all inhibit HMGCR in the same manner in terms
PR:PROJECT_SUMMARY               	of enzyme binding site, the statins’ varied physiochemical properties with
PR:PROJECT_SUMMARY               	respect to their polarity (i.e. lipophilicity) result in very different immune
PR:PROJECT_SUMMARY               	and lipid effects. The major significance of this work is to advance a new class
PR:PROJECT_SUMMARY               	of inhaler therapies for asthma; the statins which work by an entirely different
PR:PROJECT_SUMMARY               	mechanism than current ICS/LABA mainstays. Evidence suggests that statins may
PR:PROJECT_SUMMARY               	have an additive benefit to corticosteroids in asthma, thereby confirming a
PR:PROJECT_SUMMARY               	unique mechanism, namely via MVA pathway inhibition. This becomes particularly
PR:PROJECT_SUMMARY               	important in the severe asthma population which is highly
PR:PROJECT_SUMMARY               	corticosteroid-resistant, is poorly controlled with high exacerbation rates and
PR:PROJECT_SUMMARY               	hospitalizations, and has the highest healthcare costs of all asthma phenotypes.
PR:PROJECT_SUMMARY               	In essence, the potential public health impact of even an incremental
PR:PROJECT_SUMMARY               	improvement in asthma symptom control cannot be underestimated. Even the
PR:PROJECT_SUMMARY               	prevention of 1 asthma attack preserves lung function and reduces the adverse
PR:PROJECT_SUMMARY               	personal and financial impact. This study aimed to determine if statin polarity
PR:PROJECT_SUMMARY               	affects airway drug concentration and systemic drug absorption and to determine
PR:PROJECT_SUMMARY               	the effect of inhaled statins on naïve airway immune cell populations and
PR:PROJECT_SUMMARY               	alveolar-capillary membrane and epithelial barrier integrity in healthy rhesus
PR:PROJECT_SUMMARY               	monkeys. In this particular component of the study, we investigated the
PR:PROJECT_SUMMARY               	metabolic effects resulting from the use of statins in these healthy rhesus
PR:PROJECT_SUMMARY               	monkeys. Specifically, the Newman lab analyzed for lipid mediator (oxylipin,
PR:PROJECT_SUMMARY               	endocannabinoid, fatty acid, and nitro lipid) in lung and trachea tissue,
PR:PROJECT_SUMMARY               	plasma, and BAL and bile acid changes in the lung and trachea tissue and plasma.
PR:INSTITUTE                     	University of California, Davis
PR:DEPARTMENT                    	Internal Medicine
PR:LAST_NAME                     	Zeki
PR:FIRST_NAME                    	Amir
PR:ADDRESS                       	2825 J St. Suite 400 Sacramento, CA 95816
PR:EMAIL                         	aazeki@ucdavis.edu
PR:PHONE                         	(916) 734-8230
#STUDY
ST:STUDY_TITLE                   	Statin Immuno-Metabolomics in Asthma (part IV)
ST:STUDY_TYPE                    	Placebo-controled trial
ST:STUDY_SUMMARY                 	Innovative and novel therapies are urgently needed for the treatment of patients
ST:STUDY_SUMMARY                 	with severe asthma, especially those who are refractory to standard-of-care
ST:STUDY_SUMMARY                 	bronchodilators and inhaled corticosteroids. The Zeki lab is investigating the
ST:STUDY_SUMMARY                 	role of the mevalonate (MA) pathway, in the pathogenesis of airway inflammation
ST:STUDY_SUMMARY                 	and remodeling. Although statins all inhibit HMGCR in the same manner in terms
ST:STUDY_SUMMARY                 	of enzyme binding site, the statins’ varied physiochemical properties with
ST:STUDY_SUMMARY                 	respect to their polarity (i.e. lipophilicity) result in very different immune
ST:STUDY_SUMMARY                 	and lipid effects. The major significance of this work is to advance a new class
ST:STUDY_SUMMARY                 	of inhaler therapies for asthma; the statins which work by an entirely different
ST:STUDY_SUMMARY                 	mechanism than current ICS/LABA mainstays. Evidence suggests that statins may
ST:STUDY_SUMMARY                 	have an additive benefit to corticosteroids in asthma, thereby confirming a
ST:STUDY_SUMMARY                 	unique mechanism, namely via MVA pathway inhibition. This becomes particularly
ST:STUDY_SUMMARY                 	important in the severe asthma population which is highly
ST:STUDY_SUMMARY                 	corticosteroid-resistant, is poorly controlled with high exacerbation rates and
ST:STUDY_SUMMARY                 	hospitalizations, and has the highest healthcare costs of all asthma phenotypes.
ST:STUDY_SUMMARY                 	In essence, the potential public health impact of even an incremental
ST:STUDY_SUMMARY                 	improvement in asthma symptom control cannot be underestimated. Even the
ST:STUDY_SUMMARY                 	prevention of 1 asthma attack preserves lung function and reduces the adverse
ST:STUDY_SUMMARY                 	personal and financial impact. This study aimed to determine if statin polarity
ST:STUDY_SUMMARY                 	affects airway drug concentration and systemic drug absorption and to determine
ST:STUDY_SUMMARY                 	the effect of inhaled statins on naïve airway immune cell populations and
ST:STUDY_SUMMARY                 	alveolar-capillary membrane and epithelial barrier integrity in healthy rhesus
ST:STUDY_SUMMARY                 	monkeys. In this particular component of the study, we investigated the
ST:STUDY_SUMMARY                 	metabolic effects resulting from the use of statins in these healthy rhesus
ST:STUDY_SUMMARY                 	monkeys. Specifically, the Newman lab analyzed for lipid mediator (oxylipin,
ST:STUDY_SUMMARY                 	endocannabinoid, fatty acid, and nitro lipid) in lung and trachea tissue,
ST:STUDY_SUMMARY                 	plasma, and BAL and bile acid changes in the lung and trachea tissue and plasma.
ST:INSTITUTE                     	USDA
ST:DEPARTMENT                    	Obesity and metabolism research unit
ST:LABORATORY                    	Newman's Lab
ST:LAST_NAME                     	Newman
ST:FIRST_NAME                    	John
ST:ADDRESS                       	430 West Health Sciences Dr. Davis, Ca, 95616
ST:EMAIL                         	John.Newman@ars.usda.gov
ST:PHONE                         	(530) 752-1009
#SUBJECT
SU:SUBJECT_TYPE                  	Animal
SU:SUBJECT_SPECIES               	Macaca mulatta
SU:TAXONOMY_ID                   	9544
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data
SUBJECT_SAMPLE_FACTORS           	-	Zeki R 74	Tissue:Right Lung | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki R 28 Repl Avg.	Tissue:Right Lung | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki R 48	Tissue:Right Lung | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki R 68	Tissue:Right Lung | Treatment:Simvastatin	
SUBJECT_SAMPLE_FACTORS           	-	Zeki R 40	Tissue:Right Lung | Treatment:Simvastatin	
SUBJECT_SAMPLE_FACTORS           	-	Zeki R 95	Tissue:Right Lung | Treatment:Simvastatin	
SUBJECT_SAMPLE_FACTORS           	-	Zeki L 74	Tissue:Left Lung | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki L 48	Tissue:Left Lung | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki L 28 Repl Avg.	Tissue:Left Lung | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki L 95	Tissue:Left Lung | Treatment:Simvastatin	
SUBJECT_SAMPLE_FACTORS           	-	Zeki L 40	Tissue:Left Lung | Treatment:Simvastatin	
SUBJECT_SAMPLE_FACTORS           	-	Zeki L 68	Tissue:Left Lung | Treatment:Simvastatin	
SUBJECT_SAMPLE_FACTORS           	-	Zeki T 74	Tissue:Trachea | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki T 48	Tissue:Trachea | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki T 28 Repl Avg.	Tissue:Trachea | Treatment:Control	
SUBJECT_SAMPLE_FACTORS           	-	Zeki T 40	Tissue:Trachea | Treatment:Simvastatin	
SUBJECT_SAMPLE_FACTORS           	-	Zeki T 68	Tissue:Trachea | Treatment:Simvastatin	
SUBJECT_SAMPLE_FACTORS           	-	Zeki T 95	Tissue:Trachea | Treatment:Simvastatin	
#COLLECTION
CO:COLLECTION_SUMMARY            	Monkeys were treated with placebo or Provastatin for 12 days. Further, after the
CO:COLLECTION_SUMMARY            	wash out period animals were treated with Simvastatin for 12 days. Tissue were
CO:COLLECTION_SUMMARY            	collected upone animals termination at day 12 of Simvastatin treatment
CO:SAMPLE_TYPE                   	Tissue
CO:TISSUE_CELL_IDENTIFICATION    	Trachea and lung tissue
#TREATMENT
TR:TREATMENT_SUMMARY             	Monkeys were treated (by inhalation) with placebo or Provastatin for 12 days.
TR:TREATMENT_SUMMARY             	Further, after the wash out period animals were treated with Simvastatin for 12
TR:TREATMENT_SUMMARY             	days.
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	Oxylipins, endocannabinoids, bile acids and fatty acids were isolated using a
SP:SAMPLEPREP_SUMMARY            	Waters Ostro Sample Preparation Plate (Milford, MA). Lung and trachea samples
SP:SAMPLEPREP_SUMMARY            	were aliquoted (~40-60mg) into 2mL polypropylene tubes and spiked with a 5 µL
SP:SAMPLEPREP_SUMMARY            	anti-oxidant solution (0.2 mg/ml solution BHT/EDTA in 1:1 MeOH:water) and 10 μL
SP:SAMPLEPREP_SUMMARY            	1000nM analytical deuterated surrogates. A total of 50 µL of methanol, 550µL
SP:SAMPLEPREP_SUMMARY            	isopropanol w/ 10mM ammonium formate & 1% formic acid and 100 uL water were
SP:SAMPLEPREP_SUMMARY            	added and the tube was placed in a Geno/Grinder for 30 sec before being
SP:SAMPLEPREP_SUMMARY            	centrifuged at 10,000g for 5 min at room temp. The supernate was then
SP:SAMPLEPREP_SUMMARY            	transferred into the plate wells and samples were eluted into glass inserts
SP:SAMPLEPREP_SUMMARY            	containing 10 μL 20% glycerol by applying a vacuum at 15 Hg for 10 min. Eluent
SP:SAMPLEPREP_SUMMARY            	was dried by speed vacuum for 35 min at the medium BP setting, before switching
SP:SAMPLEPREP_SUMMARY            	to an aqueous setting for an additional 35 min. Once dry, samples were
SP:SAMPLEPREP_SUMMARY            	re-constituted with the internal standard 1-cyclohexyl ureido, 3-dodecanoic acid
SP:SAMPLEPREP_SUMMARY            	(CUDA) and 1-Phenyl 3-Hexadecanoic Acid Urea (PHAU) at 100 nM (50:50 MeOH:CAN),
SP:SAMPLEPREP_SUMMARY            	vortexed 1 min, transferred to a spin filter (0.1 µm, Millipore, Billerica,
SP:SAMPLEPREP_SUMMARY            	MA), centrifuged for 3 min at 6ºC at <4500g (rcf), before being transferred to
SP:SAMPLEPREP_SUMMARY            	2 mL LC-MS amber vials. Extracts were stored at -20ºC until analysis by
SP:SAMPLEPREP_SUMMARY            	UPLC-MS/MS. The internal standard was used to quantify the recovery of surrogate
SP:SAMPLEPREP_SUMMARY            	standards.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_TYPE           	Reversed phase
CH:INSTRUMENT_NAME               	Waters Acquity
CH:COLUMN_NAME                   	Aquity C18 BEH 1.7µm 100mm x 2.1mm column
CH:FLOW_GRADIENT                 	See protocol/methods file
CH:FLOW_RATE                     	0.25 mL/min
CH:COLUMN_TEMPERATURE            	60 °C
CH:SOLVENT_A                     	0.1% acetic acid
CH:SOLVENT_B                     	90% ACN / 10% IPA
CH:INTERNAL_STANDARD             	See protocol/methods file
CH:RETENTION_TIME                	See protocol/methods file
CH:SAMPLE_INJECTION              	5 µL
CH:ANALYTICAL_TIME               	20 min
CH:WEAK_WASH_SOLVENT_NAME        	20% methanol, 10% isopropanol
CH:WEAK_WASH_VOLUME              	600 µL
CH:STRONG_WASH_SOLVENT_NAME      	50:50 Acetonitrile:Methanol
CH:STRONG_WASH_VOLUME            	600 µL
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:MS_COMMENTS                   	-
MS:INSTRUMENT_NAME               	ABI Sciex 6500 QTrap
MS:INSTRUMENT_TYPE               	Triple quadrupole
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	NEGATIVE
#MS_METABOLITE_DATA
MS_METABOLITE_DATA:UNITS         	Concentration (nM)
MS_METABOLITE_DATA_START
Samples	Zeki R 74	Zeki R 28 Repl Avg.	Zeki R 48	Zeki R 68	Zeki R 40	Zeki R 95	Zeki L 74	Zeki L 48	Zeki L 28 Repl Avg.	Zeki L 95	Zeki L 40	Zeki L 68	Zeki T 74	Zeki T 48	Zeki T 28 Repl Avg.	Zeki T 40	Zeki T 68	Zeki T 95
Factors	Tissue:Right Lung | Treatment:Control	Tissue:Right Lung | Treatment:Control	Tissue:Right Lung | Treatment:Control	Tissue:Right Lung | Treatment:Simvastatin	Tissue:Right Lung | Treatment:Simvastatin	Tissue:Right Lung | Treatment:Simvastatin	Tissue:Left Lung | Treatment:Control	Tissue:Left Lung | Treatment:Control	Tissue:Left Lung | Treatment:Control	Tissue:Left Lung | Treatment:Simvastatin	Tissue:Left Lung | Treatment:Simvastatin	Tissue:Left Lung | Treatment:Simvastatin	Tissue:Trachea | Treatment:Control	Tissue:Trachea | Treatment:Control	Tissue:Trachea | Treatment:Control	Tissue:Trachea | Treatment:Simvastatin	Tissue:Trachea | Treatment:Simvastatin	Tissue:Trachea | Treatment:Simvastatin
6-keto PGF1a	1.18	8.37	1.18	0.4	0.19	1.97	2.76	1.62	16.05	2.95	0.47	0.97	2.85	0.75	1.62	2.09	1.86	4.57
TXB2	2.39	23.75	3.13	1.52	0.67	6.08	22.2	2.04	42.6	6.97	1.04	2.52	13.5	2.99	17.85	4.41	13.3	8.21
PGE1	2.04	13.15	1.58	1.74	0.32	3.8	25.8	2.09	12.4	4	0.44	4.1	7.49	2.69	1.84	4.51	7.04	11.7
PGE2	52.3	234.5	29.9	21.7	5.87	71.8	340	25.7	259.5	105	9.54	54.8	61	29.6	25.95	33.8	53	104
15-Keto PGE2	3.36	6.12	4.3	1	0.76	2.83	24.2	5.79	8.28	2.27	1.66	2.52	6.64	4.97	6.29	4.31	8.05	5.81
PGD2	51.4	368	40.8	49.4	45.6	107	194	6.75	333	92.7	1.95	91.3	56.6	2.59	28.05	55.9	19.5	109
15-deoxy PGJ2	0.8	10.31	0.08	0.19	0.11	0.99	11.4	0.48	7.51	1.78	0.3	1.45	2.84	0.79	1.23	1	1.57	3.58
PGF2a	11.3	60.85	11.5	7	3.98	15.3	28.3	6.92	60	20	5.74	18.3	25.3	4.13	8.97	8.54	14.5	16.8
11-HETE	14.9	60.95	15.1	11.3	4.92	21.3	29.5	10	68.4	27.1	5.09	17.6	17	5.71	13.4	10	16.6	21.6
Lipoxin A4	9.26	11.53	11.1	5.14	0.94	9.08	2.34	6.85	19.3	14.6	0.86	3.89	3.93	2.51	1.99	3.06	4.38	8.58
6-trans-LTB4	6.7	7.41	20.9	10.8	1.86	8.71	6.04	9.24	10.19	11.8	1.3	10.7	4.69	1.74	3.51	4.68	3.93	13
5_15-DiHETE	8.1	2.3	2.6	1.06	0.66	0.72	1.54	0.44	2.9	0.45	0.69	1.08	0.35	0.29	0.41	0.7	0.38	1.5
8_15-DiHETE	88.8	54.15	110	99.2	16.1	57.5	29.2	38.9	66.25	60.3	12.3	96.3	15.4	6.14	5.45	16.6	21.4	35
9_12_13-TriHOME	87.2	65.15	291	168	37.1	99.8	51.3	135	56.7	109	27.7	135	77.9	54.4	100	91.9	104	206
9_10-e-DiHO	8.42	40	179	19.8	7.98	79.9	23.2	52.5	28.4	19.6	14	84.6	9.78	22.8	13.15	25.1	11.8	85.8
12_13-DiHOME	1.49	1.17	5.31	1.89	3.57	3.24	1.48	2.31	1.41	2.49	4.15	2.27	1.89	2.24	1.38	6.92	2.07	2.5
9_10-DiHOME	2.53	1.75	7.96	3.24	6.05	4.62	1.85	3.24	1.96	4.71	8.24	3.75	2.98	2.67	1.99	8.06	3.35	3.29
15_16-DiHODE	2.29	1.93	6.87	2.15	5.16	3.01	1.42	6.88	1.96	3.87	6.63	2.78	3.88	4.89	2.13	12.9	5.06	2.61
9_10-DiHODE	0.08	0.07	0.2	0.11	0.18	0.21	0.06	0.11	0.04	0.19	0.23	0.14	0.07	0.06	0.05	0.35	0.1	0.13
14_15-DiHETrE	1.25	1.34	1.89	1.59	0.84	1.26	1.18	1.05	1.79	1.53	1.04	1.7	0.69	0.47	0.49	0.95	0.73	0.97
11_12-DiHETrE	0.57	0.78	0.67	0.47	0.67	0.89	0.65	0.55	0.88	1.16	0.9	0.64	0.5	0.34	0.4	0.5	0.39	0.6
8_9-DiHETrE	0.94	0.67	0.78	0.63	0.48	0.7	0.45	0.6	0.91	1.6	0.77	0.52	0.3	0.32	0.22	0.29	0.37	0.3
5_6-DiHETrE	0.45	0.52	0.56	0.14	0.33	0.44	0.3	0.24	0.45	0.6	0.36	0.31	0.1	0.34	0.12	0.31	0.21	0.18
17_18-DiHETE	38.4	16.65	10.6	6.79	14.1	14	6.01	13.3	10.41	19.3	17.8	5.64	5.98	13.9	9.37	35.1	8.04	12.9
19_20-DiHDoPA	2.53	3.13	3.2	1.36	4.39	4.17	1.43	2.6	4.9	4.17	6.77	1.93	1.46	0.54	1.41	1.93	1.17	1.78
13-HODE	4940	1449.5	9160	9840	2030	3830	1590	3010	1580	4820	1180	8570	2000	776	1320	2820	2790	4290
9-HODE	42.2	69.2	97.9	105	44.9	84.4	38.6	37.9	71.7	86.9	49.6	106	73.9	25.7	66.9	115	93.5	145
13-HOTE	266	46.4	408	587	82.8	275	80	178	44.45	375	55	467	151	32.2	69.7	199	208	358
9-HOTE	0.31	0.15	0.83	0.67	1.02	1.16	0.4	0.24	0.22	1.17	1.04	0.81	0.43	0.86	0.27	0.91	0.6	0.55
20-HETE	13	17.35	4.88	7.72	5.76	8.43	4.58	5.53	37.85	22.3	8.08	15.1	0.64	0.81	2.71	0.13	0.67	1.27
15-HETE	310	781.5	403	369	130	456	258	181	872	595	72.2	388	230	130	236.5	150	293	290
12-HETE	8790	8110	11700	8230	1920	7670	4610	5220	10800	10100	1670	9820	3030	1450	2350	2850	3500	6110
9-HETE	6.68	7.27	6.73	5.19	2.36	3.37	3.4	3.84	9.29	5.27	1.06	7.32	2.13	0.7	2.06	2.1	2.07	2.5
8-HETE	87.9	165.75	70.8	45	11.6	98.9	49.9	49.7	223	114	11.1	45.9	34.5	28.9	24.15	24.9	49.8	62.1
5-HETE	6.64	15.7	6.38	3.73	2.94	7.47	15.2	7.6	31.15	8.64	4.27	5.86	13.3	4.07	12.35	8.71	8.98	17.1
15-HEPE	115	349	145	110	40.2	205	92.5	84	160.5	337	36.7	173	35.9	27.5	25.35	32.3	67	52.7
12-HEPE	288	509.5	604	408	79.2	510	302	261	356.5	748	78.3	554	53.5	38.1	46.55	71.1	111	193
9-HEPE	7.53	6.9	7.8	3.07	1.94	6.34	5.64	5.59	9.67	9.64	1.69	5.37	0.78	0.35	0.39	0.85	1.58	2.85
5-HEPE	0.25	2.11	0.74	0.54	0.52	1.77	2.93	0.96	3.32	1.84	0.64	0.7	0.63	0.52	0.88	0.77	1.12	0.76
17-HDoHE	136	302	252	147	104	302	117	124	294	437	81.6	254	203	111	279	210	224	326
14-HDoHE	2000	2245	3590	2890	867	2520	1270	1400	2430	3130	754	3630	1200	762	1080	1170	1720	2420
4-HDoHE	1.59	0.58	0.96	0.35	0.59	1.16	0.68	2.09	2.39	1.51	0.64	1.72	3.03	0.9	4.71	1.65	1.69	6.93
9_10-EpO	13.9	13.85	44.1	11	15.7	13.3	13.8	18.6	16.95	14.9	27.5	15.6	10.9	6.99	6.96	13.3	11.4	24.1
12(13)-EpOME	6.47	7.3	8.68	11.6	18.8	13.7	6.44	7.59	6.51	12.1	19.4	14.6	8.36	9.66	5.71	17.3	13.1	9.88
9(10)-EpOME	8.97	7.49	11.8	11.2	19.7	15	7	8.2	7.86	12.3	20.3	14.9	9.64	10.8	5.26	16.9	13.8	10.7
12(13)-Ep-9-KODE	7.17	4.43	19.9	12.5	6.84	16.9	5.37	17.1	6.12	9.81	14.5	13.1	12.2	9.2	9.08	32.9	14.8	32.9
15(16)-EpODE	0.88	0.59	1.16	0.98	2.49	1.31	0.6	0.7	0.66	1.5	3.46	1.09	0.65	0.68	0.82	2.77	1.64	1.44
12(13)-EpODE	0.35	0.16	0.36	0.64	0.59	0.64	0.39	0.2	0.21	0.75	0.71	0.56	0.38	0.33	0.05	0.32	0.48	0.33
9(10)-EpODE	1.16	0.97	4.17	4.74	2.98	2.38	1.32	3.02	0.83	2.11	2.46	3.74	1.56	1.93	1.71	3.68	3.08	3.19
14(15)-EpETrE	2.63	5.56	3.19	1.3	1.94	3.05	4.81	1.94	6.26	2.78	2.51	3.37	3.61	3.77	2.4	2.31	3.36	2.68
11(12)-EpETrE	2.08	4.34	2.76	0.89	1.85	2.58	2.65	1.82	3.87	2.7	1.39	2.07	2.24	2.45	1.59	1.73	1.51	1.35
8(9)-EpETrE	2.63	5.07	3.22	1.04	1.9	2.51	1.91	2.52	4.15	2.29	1.57	2.83	2.32	3.31	11.92	4.78	3.25	5.32
19(20)-EpDPE	0.19	1.13	1.04	0.05	0.26	1.1	0.47	0.36	1.49	1.93	1.77	0.29	1.11	1.48	1.1	1.19	0.87	0.76
13-KODE	79.1	21.85	220	249	52	79.8	31.1	160	27.3	73.5	42.5	189	82.9	72.2	120	175	145	180
9-KODE	39.8	34.7	80.4	47.9	41.6	56.2	30.7	40.3	38.85	59	52.6	60.8	59.6	31.5	43.05	98	65.3	78.8
15-KETE	10.7	15.25	8.7	7.16	4.77	7.34	5.34	9.57	14	11.7	3.28	10.8	11	8.4	9.1	10.9	10.1	4.13
5-KETE	3.59	3.38	2.73	1.46	1.69	2.65	4.08	2.5	4.7	3.52	2.28	2.16	4.58	1.23	5.5	3.95	3.14	4.66
10-Nitrooleate	13.9	4.18	12.5	11.2	19.7	10.2	4.58	11.4	11.3	5.65	16.3	7.03	11.1	0.75	11.59	16.5	16.7	2.57
PGE3	0.55	9.54	0.43	0.28	0.28	4.08	10.4	1.04	7.85	4.08	0.77	1.56	0.98	0.21	0.37	0.23	0.96	1.59
LTB4																		
LTB5																		
Resolvin D1																		
12_13-DiHODE																		
14_15-DiHETE																		
17(18)-EpETE																		
14(15)-EpETE																		
11(12)-EpETE																		
16(17)-EpDPE																		
15-HpETE screen																		
12-HpETE screen																		
5-HpETE screen																		
MS_METABOLITE_DATA_END
#METABOLITES
METABOLITES_START
metabolite_name
6-keto PGF1a
TXB2
PGE1
PGE2
15-Keto PGE2
PGD2
15-deoxy PGJ2
PGF2a
11-HETE
Lipoxin A4
6-trans-LTB4
5_15-DiHETE
8_15-DiHETE
9_12_13-TriHOME
9_10-e-DiHO
12_13-DiHOME
9_10-DiHOME
15_16-DiHODE
9_10-DiHODE
14_15-DiHETrE
11_12-DiHETrE
8_9-DiHETrE
5_6-DiHETrE
17_18-DiHETE
19_20-DiHDoPA
13-HODE
9-HODE
13-HOTE
9-HOTE
20-HETE
15-HETE
12-HETE
9-HETE
8-HETE
5-HETE
15-HEPE
12-HEPE
9-HEPE
5-HEPE
17-HDoHE
14-HDoHE
4-HDoHE
9_10-EpO
12(13)-EpOME
9(10)-EpOME
12(13)-Ep-9-KODE
15(16)-EpODE
12(13)-EpODE
9(10)-EpODE
14(15)-EpETrE
11(12)-EpETrE
8(9)-EpETrE
19(20)-EpDPE
13-KODE
9-KODE
15-KETE
5-KETE
10-Nitrooleate
PGE3
LTB4
LTB5
Resolvin D1
12_13-DiHODE
14_15-DiHETE
17(18)-EpETE
14(15)-EpETE
11(12)-EpETE
16(17)-EpDPE
15-HpETE screen
12-HpETE screen
5-HpETE screen
METABOLITES_END
#END