Publication Details

Category Text Publication
Reference Category Journals
DOI 10.3390/metabo13070847
Licence creative commons licence
Title (Primary) Assessing the influence of propylthiouracil and phenytoin on the metabolomes of the thyroid, liver, and plasma in a rats
Author Wang, Z.; Haange, S.-B. ORCID logo ; Haake, V.; Huisinga, M.; Kamp, H.; Buesen, R.; Schubert, K.; Canzler, S. ORCID logo ; Hackerm├╝ller, J. ORCID logo ; Rolle-Kampczyk, U.; von Bergen, M.
Source Titel Metabolites
Year 2023
Department iDiv; MOLSYB; BIOINF
Volume 13
Issue 7
Page From art. 847
Language englisch
Topic T9 Healthy Planet
Data and Software links https://doi.org/10.5281/zenodo.5900664
Supplements https://www.mdpi.com/article/10.3390/metabo13070847/s1
Keywords thyroid hormones; propylthiouracil; phenytoin; metabolomics; hypothyroidism
Abstract The thyroid hormones (THs) regulate various physiological mechanisms in mammals, such as cellular metabolism, cell structure, and membrane transport. The therapeutic drugs propylthiouracil (PTU) and phenytoin are known to induce hypothyroidism and decrease blood thyroid hormone levels. To analyze the impact of these two drugs on systemic metabolism, we focused on metabolic changes after treatment. Therefore, in a rat model, the metabolome of thyroid and liver tissue as well as from the blood plasma, after 2-week and 4-week administration of the drugs and after a following 2-week recovery phase, was investigated using targeted LC-MS/MS and GC-MS. Both drugs were tested at a low dose and a high dose. We observed decreases in THs plasma levels, and higher doses of the drugs were associated with a high decrease in TH levels. PTU administration had a more pronounced effect on TH levels than phenytoin. Both drugs had little or no influence on the metabolomes at low doses. Only PTU exhibited apparent metabolome alterations at high doses, especially concerning lipids. In plasma, acylcarnitines and triglycerides were detected at decreased levels than in the controls after 2- and 4-week exposure to the drug, while sphingomyelins and phosphatidylcholines were observed at increased levels. Interestingly, in the thyroid tissue, triglycerides were observed at increased concentrations in the 2-week exposure group to PTU, which was not observed in the 4-week exposure group and in the 4-week exposure group followed by the 2-week recovery group, suggesting an adaptation by the thyroid tissue. In the liver, no metabolites were found to have significantly changed. After the recovery phase, the thyroid, liver, and plasma metabolomic profiles showed little or no differences from the controls. In conclusion, although there were significant changes observed in several plasma metabolites in PTU/Phenytoin exposure groups, this study found that only PTU exposure led to adaptation-dependent changes in thyroid metabolites but did not affect hepatic metabolites.
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=27226
Wang, Z., Haange, S.-B., Haake, V., Huisinga, M., Kamp, H., Buesen, R., Schubert, K., Canzler, S., Hackerm├╝ller, J., Rolle-Kampczyk, U., von Bergen, M. (2023):
Assessing the influence of propylthiouracil and phenytoin on the metabolomes of the thyroid, liver, and plasma in a rats
Metabolites 13 (7), art. 847