Intracellular localization and metabolism of the phenanthridinium trypanocide, ethidium bromide, by isolated rat hepatocytes.
1. Confocal laser scanning microscopy (CLSM) has shown that ethidium (3 ,8-diamino-5-ethyl-6-phenylphenanthridinium) bromide, an aromatic phenanthridinium trypanocide, is taken up rapidly into the nucleoli and nuclear membranes of isolated rat hepatocytes. 2. It is biotransformed by the hepatocytes and at least five metabolites have been detected by high-performance liquid chromatography (HPLC). 3. Two new metabolites, 3- and 8-N-glucuronosylethidium, have been identified by HPLC-electrospray mass spectrometry and they represent the major pathway of metabolism, accounting for 6.4 +/- 0.7 and 19.5 +/- 1.2% respectively of total recovered drug after incubation. A third metabolite, 3,8-diacetylethidium, is formed in trace quantities. 4. The other two metabolites, 3-acetylethidium and 8-acetylethidium, have been reported previously.
Tettey
J N
JN
Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, UK.
Skellern
G G
GG
Midgley
J M
JM
Grant
M H
MH
Wilkinson
R
R
Pitt
A R
AR
D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004996:Ethidium / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D010617:Phenanthridines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014344:Trypanocidal Agents / Q000378:metabolism*
D010617:Phenanthridines; D014344:Trypanocidal Agents; D004996:Ethidium