Comparative biotransformation of hexachlorobenzene and hexafluorobenzene in relation to the induction of porphyria.
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| Abstract |
The porphyrinogenic action of hexafluorobenzene was investigated and compared to that of hexachlorobenzene. Metabolite patterns in the urine of exposed rats were determined to quantify the extent of metabolism through cytochrome P450 catalysed oxidation and glutathione conjugation. Results obtained demonstrate an almost similar extent of formation of phenolic metabolites. However, in the urine of hexachlorobenzene exposed rats significantly higher levels of the N-acetyl-S-(pentahalophenyl)cysteine were observed than in the urine of hexafluorobenzene exposed rats. Hexafluorobenzene exposure did not result in induction of porphyria, whereas exposure to hexachlorobenzene did result in significantly elevated levels of urinary as well as liver porphyrins. Together these results indicate that if the reactive intermediate is indeed formed in the cytochrome P450 catalysed initial oxidative dehalogenation, the extent of its formation as well as its subsequent reactivity and reaction pathways vary with the type of the halogen substituents. Furthermore, the results seem to indicate that the extent of metabolism of hexahalogenated benzenes into urinary metabolites resulting from glutathione conjugation is a better indication of their porphyrinogenic action than their extent of metabolism to phenolic metabolites. Two explanations for this observation are presented.
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| Authors | I M Rietjens, A Steensma, C Den Besten, G van Tintelen, J Haas, B van Ommen, P J van Bladeren |
| Journal | European journal of pharmacology (Eur J Pharmacol) Vol. 293 Issue 4 Pg. 293-9 (Dec 07 1995) ISSN: 0014-2999 [Print] Netherlands |
| PMID | 8748681 (Publication Type: Comparative Study, Journal Article) |
| Chemical References |
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