Jna. Tettey et al., Intracellular localization and metabolism of the phenanthridinium trypanocide, ethidium bromide, by isolated rat hepatocytes, XENOBIOTICA, 29(4), 1999, pp. 349-360
1. Confocal laser scanning microscopy (CLSM) has shown that ethidium (3,8-d
iamino-5-ethyl-6-phenylphenanthridinium) bromide, an aromatic phenanthridin
ium trypanocide, is taken up rapidly into the nucleoli and nuclear membrane
s of isolated rat hepatocytes.
2. It is biotransformed by the hepatocytes and at least five metabolites ha
ve been detected by high-performance liquid chromatography (HPLC).
3. Two new metabolites, 3- and 8-N-glucuronosylethidium, have been identifi
ed by HPLC-electrospray mass spectrometry and they represent the major path
way of metabolism, accounting for 6.4 +/- 0.7 and 19.5 +/- 1.2% respectivel
y of total recovered drug after incubation. A third metabolite, 3,8-diacety
lethidium, is formed in tract quantities.
4. The other two metabolites, 3-acetylethidium and 8-acetylethidium, have b
een reported previously.