Overcompensation of CoA Trapping by Di(2-ethylhexyl) Phthalate (DEHP) Metabolites in Livers of Wistar Rats
Abstract
:1. Introduction
2. Results
2.1. Effects of DEHP on Diet Consumption
2.2. Effects of DEHP on Rodent Growth and Liver Weight
2.3. Effects of DEHP on CoA Ester Production
3. Discussion
3.1. DEHP Feeding Study
3.2. Physiological CoA Esters
3.3. DEHP-Derived CoA Esters Which Are Isobars of Physiological CoA Esters
3.4. Unidentified CoA Esters
3.5. Constraints on the LC-MS/MS Analyses of CoA Esters
4. Materials and Methods
4.1. Materials
4.2. DEHP Diet Preparation
4.3. GCMS Quantification of DEHP in Diet
4.4. In Vivo Experiment
4.5. LC-MS/MS Quantification of Free CoA and CoA Esters
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
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Retention Time (min) | Control nmol/g | 2% DEHP nmol/g | [DEHP]/[Control] 1 | |
---|---|---|---|---|
Free CoA and physiological CoA esters | ||||
m/z 768: Free CoA | 4.6 | 36.1 ± 3.1 | 364.3 ± 64.5 *** | 10 |
m/z 810: Acetyl-CoA | 8.1 | 97.7 ± 4.0 | 190.6 ± 18.0 *** | 2 |
m/z 824: Propionyl-CoA | 8.9 | 7.9 ± 1.1 | 18.0 ± 1.7 *** | 2 |
m/z 838: Butyryl-CoA | 9.6 | 19.8 ± 4.0 | 29.2 ± 2.4 | 1.5 |
m/z 852: Pentanoyl-CoA | 10.3 | 7.7 ± 0.7 | 11.0 ± 0.4 ** | 1.4 |
m/z 854: Malonyl-CoA | 3.2 | 0.2 ± 0.03 | 2.8 ± 0.7 ** | 18 |
m/z 854: β-hydroxybutyryl-CoA | 8.3 | 9.0 ± 1.3 | 9.1 ± 1.1 | 1.0 |
m/z 866: Hexanoyl-CoA | 11.0 | 12.0 ± 3.1 | 13.1 ± 1.8 | 1.1 |
m/z 868: Succinyl-CoA | 6.1 | 3.3 ± 0.5 | 9.2 ± 1.4 ** | 3 |
m/z 868: Methylmalonyl-CoA | 5.1 | 0.4 ± 0.1 | 1.1 ± 0.2 * | 3 |
m/z 880: Heptanoyl-CoA | 11.5 | 3.4 ± 0.3 | 4.0 ± 0.3 | 1.2 |
m/z 912: 3-Hydroxy-3-methylglutaryl-CoA | 7.3 | 5.0 ± 0.7 | 3.2 ± 0.6 | 0.6 |
m/z 922: Decanoyl-CoA | 12.8 | 0.5 ± 0.1 | 0.3 ± 0.04 | 0.6 |
m/z 1006: Palmitoyl-CoA | 14.7 | 2.2 ± 0.4 | 3.4 ± 1.0 | 2 |
Identified DEHP-derived CoA esters which are isobars of physiological CoA esters | ||||
m/z 892: 3-Octenoyl-CoA 2-Ethyl-2-hexenoyl-CoA 2-Ethyl-5-hexenoyl-CoA | 11.5 | 4.5 ± 0.4 | 53.4 ± 8.8 *** | 12 |
m/z 894: Octanoyl-CoA 2-Ethylhexanoyl-CoA | 11.6 | 11.8 ± 2.6 | 438.7 ± 59.1 *** | 37 |
m/z 908: 3-Ketooctanoyl-CoA 3-Keto-2-ethylhexanoyl-CoA | 10.7 | 0.1 ± 0.1 | 12.5 ± 1.7 ** | 98 |
m/z 910: 3-Hydroxyoctanoyl-CoA 3-Hydroxy-2-ethylhexanoyl-CoA 6-Hydroxy-2-ethylhexanoyl-CoA 5-Hydroxy-2-ethylhexanoyl-CoA | 10.3 | 1.0 ± 0.1 | 23.2 ± 3.9 ** | 22 |
Unidentified CoA esters | ||||
m/z 861: Unknown 1 | 9.4 | 0.1 ± 0.02 | 2.0 ± 0.3 *** | 14 |
m/z 862: Unknown 2 | 7.9 | 0.2 ± 0.03 | 0.7 ± 0.1 *** | 4 |
m/z 872: Unknown 3 | 10.2 | 0.1 ± 0.03 | 1.5 ± 0.2 *** | 14 |
m/z 875: Unknown 4 | 9.9 | 0.2 ± 0.03 | 2.9 ± 0.5 *** | 16 |
m/z 888: Unknown 5 | 9.7 | 0.6 ± 0.1 | 2.6 ± 0.6 *** | 4 |
m/z 904: Unknown 6 | 9.0 | 0.04 ± 0.04 | 7.1 ± 1.6 ** | 190 |
m/z 929: Unknown 7 | 9.3 | 0.02 ± 0.01 | 0.5 ± 0.1 ** | 23 |
m/z 947: Unknown 8 | 10.4 | 0.02 ± 0.01 | 0.6 ± 0.1 ** | 32 |
m/z 968: Unknown 9 | 9.5 | ND | 0.4 ± 0.1 * | - |
m/z 989: Unknown 10 | 10.9 | 0.01 ± 0.01 | 0.1 ± 0.1 | 17 |
m/z 996: Unknown 11 | 11.8 | ND | 0.2 ± 0.1 * | - |
m/z 998: Unknown 12 | 11.9 | 0.03 ± 0.02 | 0.3 ± 0.1 ** | 11 |
m/z 1008: Unknown 13 | 10.4 | ND | 0.4 ± 0.1 * | - |
m/z 1026: Unknown 14 | 8.2 | ND | 0.5 ± 0.1 * | - |
m/z 1030: Unknown 15 | 9.8 | 0.1 ± 0.1 | 9.6 ± 1.6 *** | 80 |
m/z 1052: Unknown 16 | 10.5 | ND | 0.3 ± 0.1 * | - |
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Hala, D.; Petersen, L.H.; Huggett, D.B.; Puchowicz, M.A.; Brunengraber, H.; Zhang, G.-F. Overcompensation of CoA Trapping by Di(2-ethylhexyl) Phthalate (DEHP) Metabolites in Livers of Wistar Rats. Int. J. Mol. Sci. 2021, 22, 13489. https://doi.org/10.3390/ijms222413489
Hala D, Petersen LH, Huggett DB, Puchowicz MA, Brunengraber H, Zhang G-F. Overcompensation of CoA Trapping by Di(2-ethylhexyl) Phthalate (DEHP) Metabolites in Livers of Wistar Rats. International Journal of Molecular Sciences. 2021; 22(24):13489. https://doi.org/10.3390/ijms222413489
Chicago/Turabian StyleHala, David, Lene H. Petersen, Duane B. Huggett, Michelle A. Puchowicz, Henri Brunengraber, and Guo-Fang Zhang. 2021. "Overcompensation of CoA Trapping by Di(2-ethylhexyl) Phthalate (DEHP) Metabolites in Livers of Wistar Rats" International Journal of Molecular Sciences 22, no. 24: 13489. https://doi.org/10.3390/ijms222413489