Intracellular localization and metabolism of the phenanthridinium trypanocide, ethidium bromide, by isolated rat hepatocytes

J. N.A. Tettey; G. G. Skellern; J. M. Midgley; M. H. Grant; R. Wilkinson; A. R. Pitt

doi:10.1080/004982599238551

Intracellular localization and metabolism of the phenanthridinium trypanocide, ethidium bromide, by isolated rat hepatocytes

J. N.A. Tettey, G. G. Skellern^*, J. M. Midgley, M. H. Grant, R. Wilkinson, A. R. Pitt

^*Corresponding author for this work

Analytical, Measurements and Physical Chemistry

University of Strathclyde

Research output: Contribution to journal › Article › peer-review

Abstract

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 ± 1.25% 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.

Original language	English
Pages (from-to)	349-360
Number of pages	12
Journal	Xenobiotica
Volume	29
Issue number	4
DOIs	https://doi.org/10.1080/004982599238551
Publication status	Published - 1999

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title = "Intracellular localization and metabolism of the phenanthridinium trypanocide, ethidium bromide, by isolated rat hepatocytes",

abstract = "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 ± 1.25% 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.",

author = "Tettey, {J. N.A.} and Skellern, {G. G.} and Midgley, {J. M.} and Grant, {M. H.} and R. Wilkinson and Pitt, {A. R.}",

year = "1999",

doi = "10.1080/004982599238551",

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T1 - Intracellular localization and metabolism of the phenanthridinium trypanocide, ethidium bromide, by isolated rat hepatocytes

AU - Tettey, J. N.A.

AU - Skellern, G. G.

AU - Midgley, J. M.

AU - Grant, M. H.

AU - Wilkinson, R.

AU - Pitt, A. R.

PY - 1999

Y1 - 1999

N2 - 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 ± 1.25% 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.

AB - 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 ± 1.25% 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.

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SN - 0049-8254

VL - 29

SP - 349

EP - 360

JO - Xenobiotica

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IS - 4

ER -

Intracellular localization and metabolism of the phenanthridinium trypanocide, ethidium bromide, by isolated rat hepatocytes

Abstract

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