The influence of carbamazepine on the heme biosynthetic pathway

Schoenfeld, Nili; Greenblat, Yehudit; Epstein, O; Atsmon, A

doi:10.1016/0006-2944(85)90089-4

Cited by 10 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since there are several reports of conditions under which chick-embryo hepatocytes treated with PHAs, and other compounds, accumulate URO with an associated decrease in uroporphyrinogen decarboxylase activity (Sinclair et al, 1983;Swain et al, 1983;de Verneuil et al, 1983;Nichol & Angel, 1984;Schoenfeld et al, 1985a,b), we paid particular attention to the validation of the uroporphyrinogen decarboxylase assay. The assay was shown to be linear with respect to protein concentration and incubation time for both control and TCB-treated cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Hepatic uroporphyrin accumulation and uroporphyrinogen decarboxylase activity in cultured chick-embryo hepatocytes and in Japanese quail (Coturnix coturnix japonica) and mice treated with polyhalogenated aromatic compounds

Lambrecht

Sinclair

Bement

et al. 1988

Biochemical Journal

View full text Add to dashboard Cite

The relationship between hepatic uroporphyrin accumulation and uroporphyrinogen decarboxylase (EC 4.1.1.37) activity was investigated in cultured chick-embryo hepatocytes, Japanese quail (Coturnix coturnix japonica) and mice that had been treated with polyhalogenated aromatic compounds. Chick-embryo hepatocytes treated with 3,3',4,4'-tetrachlorobiphenyl accumulated uroporphyrin in a dose-dependent fashion without a detectable decrease in uroporphyrinogen decarboxylase activity when either pentacarboxyporphyrinogen III or uroporphyrinogen III were used as substrates in the assay. Other compounds, such as hexachlorobenzene, parathion, carbamazepine and nifedipine, which have been shown previously to cause uroporphyrin accumulation in these cells, did not decrease uroporphyrinogen decarboxylase activity. Japanese quail treated with hexachlorobenzene for 7-10 days also accumulated hepatic uroporphyrin without any decrease in uroporphyrinogen decarboxylase activity. In contrast, hepatic uroporphyrin accumulation in male C57BL/6 mice treated with iron and hexachlorobenzene was accompanied by a 20-80% decrease in uroporphyrinogen decarboxylase activity, demonstrating that the assay used for uroporphyrinogen decarboxylase, using pentacarboxyporphyrinogen III as substrate, could detect decreased enzyme activity. Our results with chick hepatocytes and quail, showing uroporphyrin accumulation without a decrease in uroporphyrinogen decarboxylase activity, are consistent with a new two-stage model of the uroporphyria: initially uroporphyrinogen is oxidized by a cytochrome P-450-mediated reaction, followed in rodents by a progressive decrease in uroporphyrinogen decarboxylase activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatic uroporphyrin accumulation and uroporphyrinogen decarboxylase activity in cultured chick-embryo hepatocytes and in Japanese quail (Coturnix coturnix japonica) and mice treated with polyhalogenated aromatic compounds

Lambrecht

Sinclair

Bement

et al. 1988

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Hinweise auf einen hemmenden Effekt des Carbamazepins auf die Hämobiosynthese sind bekannt [139], Tierexperimentell wurde eine starke Zunahme der Aktivität der Delta-Aminolävulin-säure-Synthetase gefunden [243], klinisch wurde eine Carbamazepin-induzierte nicht hereditäre akute Porphyrie beschrieben [287]; andere Autoren weisen dagegen auf die Einsetzbarkeit von Carbamazepin auch bei bekannter Porphyrie hin [207]. Nachdem in tierexperimentellen Studien eine Verlängerung der atrioventrikulären Über-leitungszeit festgestellt wurde, überrascht es [128]; dabei sind extrem selten Erwachsene [255], vielmehr ganz überwiegend Kinder unter zwei Jahren betroffen und hier besonders solche unter Kombinationsbehandlung (Risikoraten bei Kindern unter zwei Jahren mit Polytherapie 1 : 500, mit Monotherapie 1 : 7000, bei Patienten über zwei Jahren mit Polytherapie 1:12000, mit Monotherapie 1:45 000) [65].…”

Section: Hypersensitivitätsreaktionenunclassified