Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework
Abstract
:1. Introduction
2. Results
2.1. Embryotoxicity
2.2. DNA Methylation
2.3. DNA Oxidation
2.4. Neurobehavioral Studies
2.5. Antioxidative Parameters
3. Discussion and Hypothesized AOP Framework
3.1. Neurobehavior
3.2. Oxidative Stress
3.3. Epigenetics
3.4. Mechanisms Leading to Methylome Alteration
3.5. Methylome Alteration via Oxidative DNA Damage
3.6. Informative Key Events (KEs)
4. Materials and Methods
4.1. General Zebrafish Maintenance and Embryo Exposures
4.2. DNA Methylation
4.3. DNA Oxidation
4.4. Neurobehavior
4.5. Oxidative Stress Defense
4.6. Statistical Analysis
4.7. Hypothesized Adverse Outcome Pathway (AOP) Framework Development
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
NCD | Non-communicable disease |
DOHaD | Developmental origins of health and disease |
SAM | S-adenosyl-l-methionine |
DNMT | DNA methyl transferase |
AOP | Adverse outcome pathway |
MIE | Molecular initiating event |
KE | Key event |
KER | Key event relationship |
dpf | Days post fertilization |
GSH | Reduced glutathione |
GSSG | Oxidized glutathione |
GPx | Glutathione peroxidase |
GR | Glutathione reductase |
SOD | Superoxide dismutase |
TTT | Total thiols |
BAP | Biological antioxidant potential |
ROS | Reactive oxygen species |
APAP | Acetaminophen, paracetamol |
CED | Critical effect dose |
8-OHdG | 8-Hydroxyl-2′-deoxyguanosine |
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Target | cyp19a2-1 | vasa-3 | vasa-5 | vtg1-3 |
---|---|---|---|---|
effect | -/↑ 164 | ↑ 61.6/- | ↑ 143/- | -/↑ 74.7 |
Parameter | Carcass (μM) | Organ (μM) |
---|---|---|
GPx | 0.46 (0.20–1.3) | 0.30 (0.04–2.8) |
GSH | 0.01 (0–0.04) | 0.04 (0–0.42) |
GSSG | 0.15 (0–1.3) | 0.47 (0.17–0.92) |
GSSG:GSH ratio | 0.01 (0–0.11) | 0.01 (0–0.54) |
TTT | 14.1 (9.16–31.09) | 0.10 (0.04–0.27) |
GR | ns | ns |
SOD | ns | ns |
BAP | ns | ns |
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Ruiter, S.; Sippel, J.; Bouwmeester, M.C.; Lommelaars, T.; Beekhof, P.; Hodemaekers, H.M.; Bakker, F.; Van den Brandhof, E.-J.; Pennings, J.L.A.; Van der Ven, L.T.M. Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework. Int. J. Mol. Sci. 2016, 17, 1830. https://doi.org/10.3390/ijms17111830
Ruiter S, Sippel J, Bouwmeester MC, Lommelaars T, Beekhof P, Hodemaekers HM, Bakker F, Van den Brandhof E-J, Pennings JLA, Van der Ven LTM. Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework. International Journal of Molecular Sciences. 2016; 17(11):1830. https://doi.org/10.3390/ijms17111830
Chicago/Turabian StyleRuiter, Sander, Josefine Sippel, Manon C. Bouwmeester, Tobias Lommelaars, Piet Beekhof, Hennie M. Hodemaekers, Frank Bakker, Evert-Jan Van den Brandhof, Jeroen L. A. Pennings, and Leo T. M. Van der Ven. 2016. "Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework" International Journal of Molecular Sciences 17, no. 11: 1830. https://doi.org/10.3390/ijms17111830