Trimethylselenonium is not the major metabolite for human cancer patients excreting high doses of selenium

Background
Perceived health benefits from taking selenium has created interest in the effect of type and dose of selenium compound administered on its metabolic pathway in the human body. Valuable information has been gained by studying the metabolites occuring in human urine.

	Recently, several studies have shown the presence of selenosugars (see left) both in rat urine and human urine, questioning earlier results that claimed trimethylselenonium ion (TMSe) to be a major metabolite. Discrepancies have been explained with different metabolic pathways depending on the concentration of selenium: one that predominates at normal exposure levels resulting primarily in the
	formation and excretion of selenosugars, and a second that is invoked at high selenium exposure and results in excretion of TMSe. However, in a earlier study made by the research group from the Graz University, marked but consistent individual variability in the amount of TMSe produced by humans were found under background and modest intake (200 µg Se) conditions.
	Since experiments under high dose conditions cannot easily be done with humans, the hypothesis of the second metabolic pathway is still unproven.

The new study
Recently high doses of selenium have been administerted as a therapetic adjunct to cancer patients undergoing normal chemotherapy. In order to test the hypothesis of a high dose metabolic pathway, the researchers from Graz University worked together with researchers from the Roswell Park Cancer Institute, investigating the selenium speciation in urine from five cancer patients receiving up to 8000 µg Se/day as L-selenomethionine over a 4-week period.

While the results of the selenium speciation obtained by HPLC-ICP-MS differed significantly for the 5 patients, some features were common: Selenosugar 1 was always the main metabolite and selenomethionine was present generally at trace concentrations only, even though the selenium was administered as L-selenomethionine.

TMSe was a significant metabolite in only one of the 5 patients: in background urine of that particular patient it was present at 3.2 µg Se/L (28.6% of identified selenium species), and after selenium intake it increased to a maximum concentration of 332 µg Se/L (11.4% of identified selenium species). For the other 4 patients TMSe was present only as a trace metabolite ranging from 0.03 to 0.2 µg Se/L (0.4% to 6.5% of identified selenium species) for background samples and increased to 1.2 to 8 µg Se/L (0.06 to 0.29% of identified selenium species) after high selenium exposure. It is interesting to note that the ratio of TMSe to selenosugars actually decreased after high selenium exposure.

These results are clearly in opposition to the hypothesis that TMSe is the major metabolite within a high-dose selenium metabolic pathway.


The original study

 Doris Kuehnelt, Dijana Juresa, Kevin A. Francesconi, Marwan Fakih, Mary E. Reid, Selenium metabolites in urine of cancer patients receiving L-selenomethionine at high doses, Toxicol. Appl. Pharmacol., 220/2 (2007) 211-215. DOI: 10.1016/j.taap.2007.01.005


 Related studies

 Bente Gammelgaard, Kenny D. Jessen, Frank H. Kristensen, Ole Jons, Determination of trimethylselenonium ion in urine by ion-chromatography and inductively coupled plasma mass spectrometry detection, Anal. Chim. Acta, 404/1 (2000) 47-54. DOI: 10.1016/S0003-2670(99)00692-3

Bente Gammelgaard, Ole Jons, Lars Bendahl, Selenium speciation in pretreated human urine by ion-exchange chromatography and ICP-MS detection, J. Anal. At. Spectrom., 16/4 (2001) 339-344. DOI: 10.1039/b008359n

Juan Manuel Marchante-Gayón, Ingo Feldmann,  Christoph Thomas, Norbert Jakubowski, Speciation of selenium in human urine by HPLC-ICP-MS with a collision and reaction cell, J. Anal. At. Spectrom., 16/5 (2001) 457-463. DOI: 10.1039/B008649P

Bente Gammelgaard, Lars Bendahl, Ulrik Sidenius, Ole Jons, Selenium speciation in urine by ion-pairing chromatography with perfluorinated carboxylic acids and ICP-MS detection, J. Anal. At. Spectrom., 17/6 (2002) 570-575. DOI: 10.1039/b202256g

Jian Zheng, Masaki Ohata, Naoki Furuta, Reversed-phase liquid chromatography with mixed ion-pair reagents coupled with ICP-MS for the direct speciation analysis of selenium compounds in human urine, J. Anal. At. Spectrom., 17/7 (2002) 730-735. DOI: 10.1039/b202531k

Yasumitsu Ogra, Kazuya Ishiwata, Hiromitsu Takayama, Norio Aimi, Kazuo T. Suzuki, Identification of a novel selenium metabolite, Se-methyl-N-acetylseleno-hexosamine, in rat urine by HPLC-ICP MS and -electrospray ionization tandem mass spectrometry, J. Chromatogr. B, 767/2 (2002) 301-312. DOI: 10.1016/S1570-0232(01)00581-5

 Jian Zheng, Yasuyuki Shibata, Atsushi Tanaka, Study of the stability of selenium compounds in human urine and determination by mixed ion-pair reversed-phase chromatography with ICP-MS detection, Anal. Bioanal. Chem., 374/2 (2002) 348-353. DOI: 10.1007/s00216-002-1425-5

Bente Gammelgaard, Kim Grimstrup Madsen, Jesper Bjerrum, Lars Bendahl, Ole Jons, Jorgen Olsen, Ulrik Sidenius, Separation, purification and identification of the major selenium metabolite from human urine by multi-dimensional HPLC-ICP-MS and APCI-MS, J. Anal. At. Spectrom., 18/1 (2003) 65-70. DOI: 10.1039/b209832f

Bente Gammelgaard, Lars Bendahl, Selenium speciation in human urine samples by LC- and CE-ICP-MS-separation and identification of selenosugars, J. Anal. At. Spectrom., 19/1 (2004) 135-142. DOI: 10.1039/b307539g

Lars Bendahl, B. Gammelgaard, Separation and identification of Se-methylselenogalactosamine - a new metabolite in basal human urine - by HPLC-ICP-MS and CE-nano-ESI-(MS)2, J. Anal. At. Spectrom., 19 (2004) 950-957. DOI: 10.1039/b406589a

Bente Gammelgaard, Lars Bendahl, Naja Wessel Jacobsen, Stefan Stürup, Quantitative determination of selenium metabolites in human urine by LC-DRC-ICP-MS, J. Anal. At. Spectrom., 20/9 (2005) 889-893. DOI: 10.1039/b504612b

Dijana Juresa, Jerome Darrouzes, Norbert Kienzl, Maite Bueno, Florence Pannier, Martine Potin-Gautier, Kevin A. Francesconi, Doris Kuehnelt, An HPLC/ICPMS study of the stability of selenosugars in human urine: implications for quantification, sample handling, and storage, J. Anal. At. Spectrom., 21/7 (2006) 684-690. DOI: 10.1039/b602976k

Doris Kuehnelt, Dijana Juresa, Norbert Kienzl, Kevin A. Francesconi, Marked individual variability in the levels of trimethylselenonium ion in human urine determined by HPLC/ICPMS and HPLC/vapor generation/ICPMS, Anal. Bioanal. Chem., 386/7-8 (2006) 2207-2212. DOI: 10.1007/s00216-006-0848-9





last time modified: August 29, 2024