| Autor: |
Haenen HE; Department of Toxicology, Agricultural University, Wageningen, The Netherlands., Rietjens IM, Vervoort J, Temmink JH, van Bladeren PJ |
| Jazyk: |
angličtina |
| Zdroj: |
Chemico-biological interactions [Chem Biol Interact] 1995 Nov 17; Vol. 98 (2), pp. 97-112. |
| DOI: |
10.1016/0009-2797(95)03637-7 |
| Abstrakt: |
Proximal tubular biotransformation of the glutathionyl (GSH) conjugate derived from 2,5-difluoronitrobenzene (5-fluoro-2-glutathionyl-nitrobenzene) was studied by means of 19F-NMR. This method allows a direct and specific detection of the fluorinated metabolites formed, at a detection limit of 1 microM for an overnight NMR run. Incubation of a monolayer of LLCPK1 cells with 100 microM 5-fluoro-2-glutathionyl-nitrobenzene for 24 h showed that these cells metabolize this GSH conjugate into the corresponding cysteinylglycyl and cysteine conjugate. The expected N-acetylcysteine conjugate however was not formed as an endproduct. Additional experiments demonstrated the absence of N-acetyltransferase activity in LLCPK1 cell lysates incubated with FCysNB and also the rapid loss of this activity in isolated renal proximal tubular cells (RPT): freshly isolated RPT cells do convert FCysNB to FNAcNB as major metabolite but, upon cultivation, quickly lose this capacity. Since uptake of FCysNB might also be a limiting factor, we investigated transport of FCysNB from the apical to the basolateral side of the culture RPT cells. No indication for such transport was obtained. Thus, the absence of mercapturic acid formation in LLCPK1 cells and cultured RPT cells is the results of a decline in N-acetyltransferase activity and perhaps a deficient cellular uptake of the cysteine conjugate. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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