Cardiovascular Effects of PCB 126 (3,3’,4,4’,5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals
Abstract
:1. Introduction
2. Results
2.1. Concentration-Dependent Cardiovascular Toxicity of PCB126
2.2. Influence of Redox-Modulators on the Cardiovascular Toxicity Induced by PCB126
2.3. Gene Expression Analysis of Oxidative Stress Related Genes
3. Discussion
4. Materials and Methods
4.1. Zebrafish Maintenance and Egg Production
4.2. Exposure to PCB126
4.3. Exposure to Redox Modulating Chemicals
4.4. Heart Rate
4.5. Stroke Volume and Cardiac Output
4.6. Peripheral Blood Flow
4.7. Pericardial Sac Area and Body Length
4.8. Quantitative RT-PCR
4.9. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
CHD | Congenital heart defects |
DLC | Dioxin-like polychlorinated biphenil |
TCDD | 2,3,7,8-tetrachlorodibenzo-p-dioxin |
PCB126 | 3,3’,4,4’,5-Pentachlorobiphenyl |
AhR | Aryl hydrocarbon receptor |
MTC | Maximum tolerable concentration |
GSH | Glutathione |
DEM | Dimethyl maleate |
NAC | N-Acetyl-L-cysteine |
TROLOX | (±)-6-Hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid |
L-NAME | Nω-Nitro-L-arginine methyl ester hydrochloride |
SNP | Sodium nitroprusside dihydrate |
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Treatment | Maximum Blood Flow (nL/min) | Minimum Blood Flow (nL/min) | Heart Rate (beats/min) | Cardiac Output (nL/min) |
---|---|---|---|---|
Control | 34.7 ± 6.8 | 5.2 ± 1.1 | 215.7 ± 3.4 | 47.0 ± 6.1 |
PCB 126 1nM | 12.1 ± 0.7 * | 3.2 ± 0.3 * | 219.4 ± 5.7 | 35.1 ± 4.4 |
PCB 126 5 nM | 4.7 ± 0.6 * | 0.8 ± 0.1 * | 215.0 ± 10.7 | 22.8 ± 1.4 ** |
PCB 126 10 nM | 2.7 ± 1.6 * | 0.4 ± 0.3 * | 226.8 ± 17.0 | 14.1 ± 4.7 *** |
PCB 126 25 nM | 1.7 ± 1.6 * | 0.1 ± 0.1 * | 209.2 ± 5.8 | 22.0 ± 5.9 ** |
Substance | CAS Number | MTC 1 (µM) | Description |
---|---|---|---|
N-Acetyl-L-cysteine (NAC) | 616-91-1 | 100 | Glutathione precursor |
Diethyl maleat (DEM) | 141-05-9 | 0.05 | Glutathione depletor |
(±)-α-Lipoic acid | 1077-28-7 | 10 | Antioxidant and free radical scavenger |
(±)-α-Tocopherol | 10191-41-0 | 100 | Antioxidant and peroxyl radical scavenger |
(±)-6-Hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (TROLOX) | 53188-07-1 | 15 | Water-soluble analogue of alpha-tocopherol |
Quercetin | 117-35-9 | 12 | Flavonoid (mitochondrial ATPase and phosphodiesterase inhibitor) |
Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) | 51298-62-5 | 100 | Inhibitor of nitric oxide synthase |
Sodium nitroprusside dihydrate (SNP) | 13755-38-9 | 250 | Nitric oxide donor |
Indomethacin | 53-86-1 | 30 | Non-steroidal anti-inflammatory compound |
Treatment | Pericardial Sac Area (% Control Vehicle area) | Body Length (% Control Vehicle Length) |
---|---|---|
Vehicle control | 100 ± 4.1 a | 100 ± 1.1 a |
DEM 50nM | 128.7 ± 3.9 a | 98.4 ± 0.5 a |
PCB126 25 nM | 329.5 ± 20.6 b | 94.1 ± 0.9 b |
PCB126 25 nM + DEM 50 nM | 302.5 ± 10.8 b | 93.7 ± 0.4 b |
Vehicle control | 100 ± 2.9 a | 100 ± 1.2 a |
NAC 100 µM | 88.3 ± 8.2 a | 101.2 ± 1.4 a |
PCB126 25 nM | 205.0 ± 21.5 b | 94.1 ± 0.5 b |
PCB126 25 nM + NAC 100 µM | 216.5 ± 24.4 b | 92.8 ± 0.9 b |
Vehicle control | 100 ± 4.9 a | 100 ± 0.8 a |
Lipoic acid 10 µM | 102.9 ± 2.9 a | 98.4 ± 1.0 a |
PCB126 25 nM | 271.6 ± 10.4 b | 93.9 ± 0.1 b |
PCB126 25 nM + lipoic acid 10 µM | 318.9 ± 39.4 b | 88.9 ± 0.8 b |
Vehicle control | 100 ± 3.1 a | 100 ± 0.1 a |
Quercetin 12 µM | 118 ± 6.4 a | 98.5 ± 0.6 a |
PCB126 25 nM | 350.5 ± 13.0 b | 91.5 ± 0.5 b |
PCB126 25 nM + quercetin 12 µM | 340.3 ± 26.4 b | 91.6 ± 1.0 b |
Vehicle control | 100 ± 10.1 a | 100 ± 0.3 a |
Indomethacin 30 µM | 114.9 ± 1.7 a | 96.5 ± 0.7 a |
PCB126 25 nM | 223.9 ± 19.2 b | 92.3 ± 0.5 b |
PCB126 25 nM + indomethacin 30 µM | 246.9 ± 22.8 b | 89.6 ± 1.3 b |
Gene | Fold Change |
---|---|
cyp1a | 199.6 ± 62.1 * |
hsp70 | 1.72 ± 0.2 * |
gpx1a | 1.21 ± 0.2 |
sod1 | 1.03 ± 0.07 |
sod2 | 1.02 ± 0.06 |
cat | 0.91 ± 0.09 |
gstp1 | 1.74 ± 0.5 * |
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Teixidó, E.; Barenys, M.; Piqué, E.; Llobet, J.M.; Gómez-Catalán, J. Cardiovascular Effects of PCB 126 (3,3’,4,4’,5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals. Int. J. Mol. Sci. 2019, 20, 1065. https://doi.org/10.3390/ijms20051065
Teixidó E, Barenys M, Piqué E, Llobet JM, Gómez-Catalán J. Cardiovascular Effects of PCB 126 (3,3’,4,4’,5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals. International Journal of Molecular Sciences. 2019; 20(5):1065. https://doi.org/10.3390/ijms20051065
Chicago/Turabian StyleTeixidó, Elisabet, Marta Barenys, Ester Piqué, Joan M. Llobet, and Jesús Gómez-Catalán. 2019. "Cardiovascular Effects of PCB 126 (3,3’,4,4’,5-Pentachlorobiphenyl) in Zebrafish Embryos and Impact of Co-Exposure to Redox Modulating Chemicals" International Journal of Molecular Sciences 20, no. 5: 1065. https://doi.org/10.3390/ijms20051065