A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Model of Advanced Chronic Liver Disease
2.2. Docosahexaenoic Acid Administration
2.3. In Vivo Hemodynamic Analysis
2.4. Biochemical Analysis
2.5. Liver Histology
2.6. Oil Red O Staining
2.7. Immunofluorescence
2.8. Cell Culture and Docosahexaenoic Acid Treatment
2.9. RNA Isolation and Quantitative PCR
2.10. Western Blot Analysis
2.11. Statistical Analysis
3. Results
3.1. Hepatic Fatty Acid Profile Is Deregulated in Rats with ACLD
3.2. Treatment with DHA Reestablishes a Healthy Lipid Profile
3.3. DHA Ameliorates Portal Hypertension in Rats with ACLD
3.4. DHA Reduces Oxidative Stress and Inflammation
3.5. DHA Promotes HSC Deactivation in Rats with ACLD
3.6. DHA Promotes Deactivation of Human HSC
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Fatty Acid | Healthy Vehicle | Healthy DHA | Cirrhotic Vehicle | Cirrhotic DHA |
---|---|---|---|---|
SFA | ||||
MA (14:0) | 0.39 ± 0.04 | 0.31 ± 0.03 | 0.43 ± 0.01 | 0.30 ± 0.02 ** |
PA (C16:0) | 21.09 ± 0.31 | 21.48 ± 0.67 | 23.28 ± 0.41 ### | 24.58 ± 0.39 |
SA (C18:0) | 17.82 ± 0.26 | 17.40 ± 0.72 | 14.43 ± 0.88### | 16.02 ± 0.54 |
MUFA | ||||
POA (C16:1 n-7) | 1.74 ± 0.17 | 1.68 ± 0.22 | 2.64 ± 0.30 | 1.74 ± 2.13 * |
OA (C18:1 n-9) | 8.40 ± 0.54 | 7.33 ± 0.40 | 15.70 ± 1.32 ### | 8.87 ± 0.22 *** |
VAC (C18:1 n-7) | 3.77 ± 0.29 | 3.03 ± 0.10 | 3.36 ± 0.16 | 2.85 ± 0.16 |
EIA (C20:1 n-9) | 0.13 ± 0.01 | 0.11 ± 0.01 | 0.12 ± 0.01 | 0.12 ± 0.01 |
NA (C24:1 n-9) | 0.27 ± 0.02 | 0.24 ± 0.01 | 0.29 ± 0.03 | 0.34 ± 0.03 |
PUFA | ||||
n-3 series | ||||
ALA (C18:3 n-3) | 0.40 ± 0.04 | 0.43 ± 0.05 | 0.40 ± 0.03 | 0.25 ± 0.02 *** |
ETE (C20:3 n-3) | 0.30 ± 0,02 | 0.22 ± 0.02 * | 0.28 ± 0.02 | 0.13 ± 0.02 ** |
EPA (C20:5 n-3) | 0.18 ± 0.03 | 1.4 ± 0.26 ** | 0.11 ± 0.02 | 1.25 ± 0.08 *** |
DPA (C22:5 n-3) | 0.59 ± 0.03 | 1.41 ± 0.16 ** | 0.64 ± 0.03 | 1.42 ± 0.08 *** |
DHA (C22:6 n-3) | 5.85 ± 0.48 | 9.82 ± 0.52 ** | 1.97 ± 0.25 ### | 11.70 ± 0.45 *** |
n-6 series | ||||
LA (C18:2 n-6) | 17.63 ± 0.54 | 18.37 ± 0.31 | 18.13 ± 0.42 | 17.32 ± 0.29 |
GLA (C18:3 n-6) | 0.16 ± 0.01 | 0.11 ± 0.01 * | 0.32 ± 0.02 | 0.08 ± 0.01 *** |
HGLA (C20:3 n-6) | 0.52 ± 0.05 | 0.84 ± 0.05 *** | 0.,32 ± 0.02 | 0.82 ± 0.05 *** |
AA (C20:4 n-6) | 18.59 ± 0.32 | 14.76 ± 0.72 *** | 14.86 ± 0.90 ### | 10.25 ± 0.34 *** |
DTA (C22:4 n-6) | 0.49 ± 0.02 | 0.20 ± 0.02 *** | 0.73 ± 0.07 | 0.21 ± 0.01 *** |
DPA (C22:5 n-6) | 0.26 ± 0.01 | 0.20 ± 0.02 | 1.07 ± 0.18 | 0.24 ± 0.02 *** |
Total SFA | 40.26 ± 0.54 | 40.11 ± 0.90 | 39.01 ± 0.53 | 42.07 ± 0.35 *** |
Total MUFA | 14.31 ± 0.93 | 12.34 ± 0.56 | 22.11 ± 1.55 ### | 13.93 ± 0.36 *** |
Total PUFA | 45.44 ± 0.97 | 47.50 ± 0.74 | 38.88 ± 1.08 ### | 43.99 ± 0.37 *** |
Total n-3 FA | 7.32 ± 0.54 | 12.94 ± 0.86 *** | 3.11 ± 0.24 ### | 14.74 ± 0.47 *** |
Total n-6 FA | 38.11 ± 0.76 | 34.55 ± 0.65 *** | 35.77 ± 0.85 | 29.26 ± 0.33 *** |
Ratios | Healthy Vehicle | Healthy DHA | Cirrhotic Vehicle | Cirrhotic DHA |
---|---|---|---|---|
SFA/MUFA | 2.86 ± 0.44 | 3.27 ± 0.48 | 1.81 ± 0.34 ### | 3.04 ± 0.30 *** |
MUFA/PUFA | 0.32 ± 0.06 | 0.26 ± 0.03 | 0.58 ± 0.13 ## | 0.32 ± 0.03 *** |
ω-6/ω-3 | 5.32 ± 0.88 | 2.72 ± 0.46 ** | 11.72 ± 1.56 ### | 2.01 ± 0.26 *** |
ω-3 INDEX (DHA + EPA) | 6.03 ± 1.09 | 11.15 ± 1.64 *** | 2.08 ± 0.57 ### | 12.95 ± 1.49 *** |
AA/EPA | 108.3 ± 25.2 | 12.74 ± 5.69 *** | 156.0 ± 24.2 ### | 8.65 ± 2.35 *** |
AA/DHA | 3.26 ± 0.58 | 1.50 ± 0.33 *** | 7.87 ± 1.41 ### | 0.90 ± 0.18 *** |
Δ5 (C20:4 n-6/C20:3 n-6) | 36.99 ± 3.95 | 17.39 ± 1.152 *** | 47.55 ± 2.12 | 12.09 ± 0.85 *** |
Δ6 (C20:3 n-6/C18:2 n-6) | 2.99 ± 0.31 | 4.58 ± 0.27 | 1.76 ± 0.10 | 4.76 ± 0.31 *** |
SCD1 INDEX (C16:1 n-7/C18:1 n-9) | 20.72 ± 1.81 | 22.98 ± 2.79 | 16.80 ± 1.33 | 19.74 ± 1.51 |
SCD16 INDEX (C16:1 n-7/C16:0) | 8.24 ± 0.81 | 7.73 ± 0.78 | 11.30 ± 1.17 | 7.08 ± 0.49 |
SCD18 INDEX (C18:1 n-9/C18:0) | 47.32 ± 3.70 | 42.72 ± 3.76 | 111.6 ± 14.1 ### | 56.02 ± 2.63 *** |
C18:2 n-6/C20:4 n-6 | 0.95 ± 0.02 | 1.29 ± 0.08 | 1.24 ± 0.09 | 1.71 ± 0.08 |
C18:0/C16:0 | 0.85 ± 0.01 | 0.81 ± 0.04 | 0.62 ± 0.05 # | 0.66 ± 0.03 |
C24:0/C22:0 | 2.82 ± 0.12 | 3.39 ± 0.20 | 2.53 ± 0.22 | 3.01 ± 0.12 |
C24:0/C20:0 | 7.77 ± 0.73 | 7.28 ± 0.58 | 3.90 ± 0.35 # | 5.73 ± 0.35 |
C18:1 n-7/C16:1 n-7 | 2.22 ± 0,18 | 1.92 ± 0.23 | 1.34 ± 0.17 | 1.67 ± 0.11 ** |
Parameter | Vehicle | DHA | p Value |
---|---|---|---|
PP (mmHg) | 13.91 ± 0.60 | 12.05 ± 0.57 | 0.03 |
PBF (mL·min−1) | 15.66 ± 2.54 | 18.21 ± 2.31 | >0.20 |
IHVR (mmHg·min·mL−1) | 1.05 ± 0.15 | 0.79 ± 0.11 | 0.16 |
SMABF (mL·min−1) | 8.37 ± 0.91 | 10.03 ± 1.45 | >0.20 |
MAP (mmHg) | 116.23 ± 5.40 | 99.92 ± 6.25 | 0.1 |
HR (beats·min−1) | 415 ± 13 | 383 ± 17 | 0.15 |
AST (U/L) | 155.8 ± 17.08 | 115.8 ± 9.05 | 0.04 |
Albumin (U/L) | 31.2 ± 0.32 | 30.27 ± 0.53 | >0.20 |
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Boyer-Diaz, Z.; Domingo, J.C.; De Gregorio, E.; Manicardi, N.; Aristu-Zabalza, P.; Cordobilla, B.; Abad-Jordà, L.; Ortega-Ribera, M.; Fernández-Iglesias, A.; Marí, M.; et al. A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease. Nutrients 2019, 11, 2358. https://doi.org/10.3390/nu11102358
Boyer-Diaz Z, Domingo JC, De Gregorio E, Manicardi N, Aristu-Zabalza P, Cordobilla B, Abad-Jordà L, Ortega-Ribera M, Fernández-Iglesias A, Marí M, et al. A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease. Nutrients. 2019; 11(10):2358. https://doi.org/10.3390/nu11102358
Chicago/Turabian StyleBoyer-Diaz, Zoe, Joan Carles Domingo, Estefanía De Gregorio, Nicolò Manicardi, Peio Aristu-Zabalza, Begoña Cordobilla, Laia Abad-Jordà, Martí Ortega-Ribera, Anabel Fernández-Iglesias, Montserrat Marí, and et al. 2019. "A Nutraceutical Rich in Docosahexaenoic Acid Improves Portal Hypertension in a Preclinical Model of Advanced Chronic Liver Disease" Nutrients 11, no. 10: 2358. https://doi.org/10.3390/nu11102358