The porphyrogenic effects of calcium channel blocking drugs

1985 ◽  
Vol 69 (5) ◽  
pp. 581-586 ◽  
Author(s):  
N. Schoenfeld ◽  
J. Aelion ◽  
Y. Beigel ◽  
O. Epstein ◽  
A. Atsmon
Keyword(s):  
Chick Embryo ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Decarboxylase Activity ◽  
Blocking Drug ◽  
Slight Effect ◽  
Uroporphyrinogen Decarboxylase ◽  
Channel Blocking

1. Treatment of monolayers of chick embryo hepatocytes with the calcium channel blocking drugs nifedipine and verapamil resulted in a decrease in the activity of uroporphyrinogen decarboxylase, an increase in the activity of δ-aminolaevulinate synthase and accumulation of porphyrins with uroporphyrin and heptacarboxylic porphyrin predominating. 2. Diltiazem, another calcium channel blocking drug, did not affect uroporphyrinogen decarboxylase activity and had a slight effect only on the accumulation of porphyrins. 3. Experiments with nifedipine and verapamil in the presence of various concentrations of calcium indicate that the porphyrogenic effect is apparently not related to blocking of calcium channels.

scholarly journals CARDIO NEUROLOGICAL SYMPTOMS CAUSED BY AN ACUTE POISONING WITH SLOW CALCIUM CHANNEL BLOCKING AGENT (VERAPAMIL)

2020 ◽  
Vol 26 (4) ◽  
pp. 34-39
Author(s):  
Boris Borisovich Yatsinyuk ◽  
◽  
Pavel Pavlovich Gavrikov ◽  
Yulia Vasilyevna Lobur
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Blocking Agent ◽  
Acute Poisoning ◽  
Frequency Of Occurrence ◽  
Hemodynamic Parameters ◽  
Hemodynamic Effects ◽  
Channel Blocking ◽  
Consciousness Disorder ◽  
Calcium Channels Blockers

The research of an analysis of the cardiac hemodynamic effects of an acute chemical trauma with slow calcium channels blockers (verapamil) shows that the depth of disorder of cardiac hemodynamic parameters and the level and frequency of occurrence of consciousness disorder were determined in 46 patients within the period of 2007–2017 in this nosological form of acute poisoning.

scholarly journals 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

1988 ◽  
Vol 253 (1) ◽  
pp. 131-138 ◽  
Author(s):  
R W Lambrecht ◽  
P R Sinclair ◽  
W J Bement ◽  
J F Sinclair ◽  
H M Carpenter ◽  
...  
Keyword(s):  
Chick Embryo ◽  
Japanese Quail ◽  
Aromatic Compounds ◽  
Coturnix Japonica ◽  
Decarboxylase Activity ◽  
Coturnix Coturnix Japonica ◽  
Uroporphyrinogen Decarboxylase ◽  
Coturnix Coturnix ◽  
Dose Dependent Fashion ◽  
The Relationship

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.

scholarly journals Inhibition of uroporphyrinogen decarboxylase by halogenated biphenyls in chick hepatocyte cultures. Essential role for induction of cytochrome P-448

1984 ◽  
Vol 222 (3) ◽  
pp. 737-748 ◽  
Author(s):  
P R Sinclair ◽  
W J Bement ◽  
H L Bonkovsky ◽  
J F Sinclair
Keyword(s):  
Chick Embryo ◽  
Dose Response ◽  
Essential Role ◽  
Piperonyl Butoxide ◽  
Polycyclic Hydrocarbon ◽  
Decarboxylase Activity ◽  
Uroporphyrinogen Decarboxylase ◽  
Maximal Induction ◽  
Time Required ◽  
Cytochrome P 450

Uroporphyrinogen decarboxylase (EC 4.1.1.37) activity was assayed in cultures of chick-embryo hepatocytes by the changes in composition of porphyrins accumulated after addition of excess 5-aminolaevulinate. Control cells accumulated mainly protoporphyrin, whereas cells treated with 3,4,3′,4′-tetrachlorobiphenyl or 2,4,5,3′,4′-pentabromobiphenyl accumulated mainly uroporphyrin, indicating decreased activity of the decarboxylase. 3-Methylcholanthrene and other polycyclic-hydrocarbon inducers of the P-448 isoenzyme of cytochrome P-450, did not affect the decarboxylase in the absence of the biphenyls. Induction of P-448 was detected as an increase in ethoxyresorufin de-ethylase activity. Pretreatment of cells with methylcholanthrene decreased the time required for the halogenated biphenyls to inhibit the decarboxylase. The dose response of methylcholanthrene showed that less than 40% of the maximal induction of cytochrome P-448 was needed to produce the maximum biphenyl-mediated inhibition of the decarboxylase. In contrast, induction of the cytochrome P-450 isoenzyme by propylisopropylacetamide had no effect on the biphenyl-mediated decrease in decarboxylase activity. Use of inhibitors of the P-450 and P-448 isoenzymes (SKF-525A, piperonyl butoxide and ellipticine) supported the concept that only the P-448 isoenzyme is involved in the inhibition of the decarboxylase by the halogenated biphenyls. The effect of preinduction with methylcholanthrene to enhance inhibition of the decarboxylase was also shown by the increased rate at which porphyrin accumulated from endogenously synthesized 5-aminolaevulinate after treatment of cells with the combination of propylisopropylacetamide and the biphenyls. Antioxidants, chelators of iron, and chromate affected the decrease in decarboxylase activity only if they prevented the induced increase in cytochrome P-448. We conclude that the P-448 and not the P-450 isoenzyme of cytochrome P-450 plays an obligatory role in the inhibition of uroporphyrinogen decarboxylase caused by halogenated biphenyls.

scholarly journals Inhibition of uroporphyrinogen decarboxylase activity. The role of cytochrome P-450-mediated uroporphyrinogen oxidation

1990 ◽  
Vol 269 (2) ◽  
pp. 437-441 ◽  
Author(s):  
R W Lambrecht ◽  
J M Jacobs ◽  
P R Sinclair ◽  
J F Sinclair
Keyword(s):  
Chick Embryo ◽  
Fold Increase ◽  
Treated Mouse ◽  
Decarboxylase Activity ◽  
Chick Embryos ◽  
Uroporphyrinogen Decarboxylase ◽  
Chemically Induced ◽  
Cytochrome P 450 ◽  
Generating System

It was previously shown that uroporphyrinogen oxidation is catalysed by a form of cytochrome P-450 induced by 3-methylcholanthrene [Sinclair, Lambrecht & Sinclair (1987) Biochem. Biophys. Res. Commun. 146, 1324-1329]. We have now measured uroporphyrinogen oxidation and uroporphyrinogen decarboxylation simultaneously in 10,000 g supernatants from the livers of methylcholanthrene-treated mice and chick embryos incubated with an NADPH-generating system. We found that uroporphyrinogen oxidation is associated with inhibition of uroporphyrinogen decarboxylase activity. The decreased uroporphyrinogen decarboxylase activity was not due to depletion of substrate, since decarboxylase activity was not increased by a 2.6-fold increase in uroporphyrinogen. Uroporphyrinogen oxidation and the associated inhibition of decarboxylase activity were also observed with liver supernatant from methylcholanthrene-treated chick embryo; both actions required the addition of 3,3′,4,4′-tetrachlorobiphenyl. Uroporphyrinogen oxidation catalysed by microsomes from a methylcholanthrene-treated mouse inhibited the uroporphyrinogen decarboxylase activity in the 100,000 g supernatant. Ketoconazole, an inhibitor of cytochrome P-450, prevented both uroporphyrinogen oxidation and the inhibition of uroporphyrinogen decarboxylation. The addition of ketoconazole to mouse supernatant actively oxidizing uroporphyrinogen inhibited the oxidation and restored decarboxylation. The latter finding suggested that a labile inhibitor was formed during the oxidation. These results suggest uroporphyrinogen oxidation may be important in the mechanism of chemically induced uroporphyria.

Sign in / Sign up

Export Citation Format

Share Document