Inhibition of ferrochelatase and accumulation of porphyrins in mouse hepatocyte cultures exposed to porphyrinogenic chemicals.
作者： Angela M. Brady , Edward A. Lock
DOI: 10.1007/BF01974011
关键词:
摘要: The ability of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine (EDDC) and griseofulvin to induce porphyria in primary cultures mouse hepatocytes has been examined. Exposure cultured DDC, EDDC or resulted a marked inhibition ferrochelatase which was sustained over the 4-day exposure period. Maximal concentrations DDC (25 μM), μM) 14-fold, 30-fold 9-fold increases, respectively, total porphyrin culture medium. Analysis porphyrins accumulating indicated predominance protoporphyrin with all three xenobiotics. Addition 5-aminolaevulinic acid (ALA) hepatocyte (10–1000 much larger increases (up 164-fold) accumulation medium predominantly uroporphyrin. These studies have demonstrated that provide valid mechanism-based vitro model hepatic porphyrias produced by dihydropyridines mice.
springer.com
sci-hub.se 参考文章(25)
Jinichi Onisawa, Robert F. Labbe, Effects of diethyl-1, 4-dihydro-2, 4,6-trimethylpyridine-3,5-dicarboxylate on the metabolism of porphyrins and iron. Journal of Biological Chemistry. ,vol. 238, pp. 724- 727 ,(1963) , 10.1016/S0021-9258(18)81326-6
F DE MATTEIS, BE PRIOR, Experimental hepatic porphyria caused by feeding 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine. Comparison with sedormid porphyria. Biochemical Journal. ,vol. 83, pp. 1- 8 ,(1962) , 10.1042/BJ0830001
D.J. Randall, W.S. Hoar, 8 - Special Techniques Fish Physiology. ,vol. 6, pp. 511- 528 ,(1971) , 10.1016/S1546-5098(08)60153-3
Francesco De Matteis, Giuseppe Abbritti, Anthony H. Gibbs, Decreased liver activity of porphyrin–metal chelatase in hepatic porphyria caused by 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Studies in rats and mice Biochemical Journal. ,vol. 134, pp. 717- 727 ,(1973) , 10.1042/BJ1340717
F. de Matteis, C. Hollands, A.H. Gibbs, N. de Sa, M. Rizzardini, Inactivation of cytochrome P-450 and production of N-alkylated porphyrins caused in isolated hepatocytes by substituted dihydropyridines. Structural requirements for loss of haem and alkylation of the pyrrole nitrogen atom. FEBS Letters. ,vol. 145, pp. 87- 92 ,(1982) , 10.1016/0014-5793(82)81212-X
F. De Matteis, A.H. Gibbs, P.B. Farmer, J.H. Lamb, Liver production of N-alkylated porphyrins caused in mice by treatment with substituted dihydropyridines. Evidence that the alkyl group on the pyrrole nitrogen atom originates from the drug. FEBS Letters. ,vol. 129, pp. 328- 331 ,(1981) , 10.1016/0014-5793(81)80194-9
Giuseppe Abbritti, Francesco De Matteis, Decreased levels of cytochrome P-450 and catalase in hepatic porphyria caused by substituted acetamides and barbiturates. Importance of the allyl group in the molecule of the active drugs. Chemico-Biological Interactions. ,vol. 4, pp. 281- 286 ,(1972) , 10.1016/0009-2797(72)90022-1
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
F. Matteis, C. Rimington, Disturbance of porphyrin metabolism caused by griseofulvin in mice. British Journal of Dermatology. ,vol. 75, pp. 91- 104 ,(1963) , 10.1111/J.1365-2133.1963.TB13945.X
G. Elder, Enzymatic defects in porphyria: an overview. Seminars in Liver Disease. ,vol. 2, pp. 87- 99 ,(1982) , 10.1055/S-2008-1040699