Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene

1. 1. It has been reported that hexachlorobenzene (HCB) in vivo produces hepatic porphyrinogen carboxy-lyase (PCL) decrease and pentachlorophenol (PCP) is one of its metabolites. In order to investigate if such decrease is due to an enzyme inhibitor present in the porphyric livers, the effects of th...

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Publicado: 1980
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0020711X_v12_n5-6_p1027_DeMolina
http://hdl.handle.net/20.500.12110/paper_0020711X_v12_n5-6_p1027_DeMolina
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spelling paper:paper_0020711X_v12_n5-6_p1027_DeMolina2023-06-08T14:41:01Z Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene 2,4 dinitrophenol hexachlorobenzene pentachlorophenol animal experiment drug identification drug induced disease enzyme inhibition hepatic porphyria liver oral drug administration porphyrinogen carboxylase preliminary communication rat tetrachlorophenol Animal Benzene Biotransformation Carboxy-Lyases Chorionic Gonadotropin Coproporphyrinogens Female Hexachlorobenzene Liver Pentachlorophenol Porphyrinogens Rats Structure-Activity Relationship Support, Non-U.S. Gov't 1. 1. It has been reported that hexachlorobenzene (HCB) in vivo produces hepatic porphyrinogen carboxy-lyase (PCL) decrease and pentachlorophenol (PCP) is one of its metabolites. In order to investigate if such decrease is due to an enzyme inhibitor present in the porphyric livers, the effects of the following additions on the normal rat liver PCL activity were investigated: (a) a porphyric liver preparation (free of porphyrins), (b) a heat deproteinized porphyric liver preparation, (c) HCB, PCP, several chloro and nitrophenols and other related compounds. 2. 2. The results of (a) and (b) would indicate that in porphyric liver there is probably an inhibitor tightly bound to the "porphyric" enzyme which is not separated by Sephadex G-25 and that produces an inhibition of "normal" enzyme smaller than that observed in vivo for HCB, the difference being perhaps due to a protein synthesis level action. 3. 3. From the results of (c) it is observed that (i) there are several drugs that inhibit hepatic PCL in different degrees, PCP, tetrachlorophenol and 2,4-dinitrophenol being the most effective, while HCB has no effect at any of the assayed concentrations, (ii) the inhibitory effect of these compounds could be mainly due to the presence of phenolic group and increased by the presence of electrophilic groups in the benzene ring, (iii) the above mentioned inhibitor made evident by the heating assays could be PCP, HCB being discarded because the absence of effect. However, the marked inhibitory effect of PCP decreases and disappears at lower concentrations. 4. 4. The physiological role of PCP in the production mechanism of HCB porphyria is discussed. © 1980. 1980 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0020711X_v12_n5-6_p1027_DeMolina http://hdl.handle.net/20.500.12110/paper_0020711X_v12_n5-6_p1027_DeMolina
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic 2,4 dinitrophenol
hexachlorobenzene
pentachlorophenol
animal experiment
drug identification
drug induced disease
enzyme inhibition
hepatic porphyria
liver
oral drug administration
porphyrinogen carboxylase
preliminary communication
rat
tetrachlorophenol
Animal
Benzene
Biotransformation
Carboxy-Lyases
Chorionic Gonadotropin
Coproporphyrinogens
Female
Hexachlorobenzene
Liver
Pentachlorophenol
Porphyrinogens
Rats
Structure-Activity Relationship
Support, Non-U.S. Gov't
spellingShingle 2,4 dinitrophenol
hexachlorobenzene
pentachlorophenol
animal experiment
drug identification
drug induced disease
enzyme inhibition
hepatic porphyria
liver
oral drug administration
porphyrinogen carboxylase
preliminary communication
rat
tetrachlorophenol
Animal
Benzene
Biotransformation
Carboxy-Lyases
Chorionic Gonadotropin
Coproporphyrinogens
Female
Hexachlorobenzene
Liver
Pentachlorophenol
Porphyrinogens
Rats
Structure-Activity Relationship
Support, Non-U.S. Gov't
Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene
topic_facet 2,4 dinitrophenol
hexachlorobenzene
pentachlorophenol
animal experiment
drug identification
drug induced disease
enzyme inhibition
hepatic porphyria
liver
oral drug administration
porphyrinogen carboxylase
preliminary communication
rat
tetrachlorophenol
Animal
Benzene
Biotransformation
Carboxy-Lyases
Chorionic Gonadotropin
Coproporphyrinogens
Female
Hexachlorobenzene
Liver
Pentachlorophenol
Porphyrinogens
Rats
Structure-Activity Relationship
Support, Non-U.S. Gov't
description 1. 1. It has been reported that hexachlorobenzene (HCB) in vivo produces hepatic porphyrinogen carboxy-lyase (PCL) decrease and pentachlorophenol (PCP) is one of its metabolites. In order to investigate if such decrease is due to an enzyme inhibitor present in the porphyric livers, the effects of the following additions on the normal rat liver PCL activity were investigated: (a) a porphyric liver preparation (free of porphyrins), (b) a heat deproteinized porphyric liver preparation, (c) HCB, PCP, several chloro and nitrophenols and other related compounds. 2. 2. The results of (a) and (b) would indicate that in porphyric liver there is probably an inhibitor tightly bound to the "porphyric" enzyme which is not separated by Sephadex G-25 and that produces an inhibition of "normal" enzyme smaller than that observed in vivo for HCB, the difference being perhaps due to a protein synthesis level action. 3. 3. From the results of (c) it is observed that (i) there are several drugs that inhibit hepatic PCL in different degrees, PCP, tetrachlorophenol and 2,4-dinitrophenol being the most effective, while HCB has no effect at any of the assayed concentrations, (ii) the inhibitory effect of these compounds could be mainly due to the presence of phenolic group and increased by the presence of electrophilic groups in the benzene ring, (iii) the above mentioned inhibitor made evident by the heating assays could be PCP, HCB being discarded because the absence of effect. However, the marked inhibitory effect of PCP decreases and disappears at lower concentrations. 4. 4. The physiological role of PCP in the production mechanism of HCB porphyria is discussed. © 1980.
title Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene
title_short Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene
title_full Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene
title_fullStr Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene
title_full_unstemmed Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene
title_sort investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene
publishDate 1980
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0020711X_v12_n5-6_p1027_DeMolina
http://hdl.handle.net/20.500.12110/paper_0020711X_v12_n5-6_p1027_DeMolina
_version_ 1768541969739415552