Comparative disposition of dimethylaminoethanol and choline in rats and mice following oral or intravenous administration
| Autor: | C.E. Garner, J. M. Sanders, Suramya Waidyanatha, K.A. Shipkowski, Christopher J. Wegerski, M. Doyle-Eisele, Jacob D. McDonald |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Administration Oral Absorption (skin) Urine Pharmacology Toxicology Article Choline Dimethylnitrosamine Excretion 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine In vivo Animals Tissue Distribution Rats Wistar Carcinogen ADME Deanol Metabolism Rats 030104 developmental biology chemistry 030220 oncology & carcinogenesis Administration Intravenous Female |
| Zdroj: | Toxicol Appl Pharmacol |
| Popis: | Dimethylaminoethanol (DMAE) and its salts have been used to treat numerous disorders in humans and hence safety of its use is a concern. DMAE is a close structural analog of choline, an essential nutrient. Exposure to DMAE may affect choline uptake and synthesis. The current investigation characterizes :1) the absorption, distribution, metabolism, and excretion (ADME) of DMAE in Wistar Han rats and B6C3F1 mice following a single gavage or intravenous (IV) administration of 10, 100 or 500 mg/kg [(14)C]DMAE, and 2) the ADME of [(14)C]choline (160 mg/kg) and the effect on its disposition following pre-treatment with DMAE (100 or 500 mg/kg). In both rats and mice, following gavage administration, DMAE was excreted in urine (16–69%) and as exhaled CO(2) (3–22%). The tissue retention was moderate (21–44%); however, the brain concentrations were low and there was no accumulation. Serum choline levels were not elevated following administration of DMAE. The DMAE metabolites in urine were DMAE N-oxide and N,N-dimethylglycine; the carcinogen, N-N-dimethylnitrosamine, was not detected. The pattern of disposition of [(14)C]choline following gavage administration was similar to that of [(14)C]DMAE. Prior treatment with DMAE had minimal effects on choline disposition. The pattern of disposition of [(14)C]DMAE and [(14)C]choline following IV administration was similar to gavage administration. There were minimal dose-, sex- or species-related effects following gavage or IV administration of [(14)C]DMAE or [(14)C]choline. Data from the current study did not support previous reports that: 1) DMAE alters choline uptake and distribution, or 2) that DMAE is converted into choline in vivo. |
| Databáze: | OpenAIRE |
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