Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment

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The effect of a pretreatment with phenobarbitone (PB) on the porphyrinogenic action exerted by hexachlorobenzene (HCB) was examined in female rats. Kinetic studies of enzyme function after HCB poisoning showed that porphyrinogen carboxy-lyase was the only enzyme of haem biosynthesis that markedly lo...

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Autores principales: Wainstok de Calmanovici, R., Del Rios de Molina, C.M., Taira de Yamasato, M.C.
Formato: JOUR
Materias:
hexachlorobenzene
liver enzyme
phenobarbital
animal experiment
drug intoxication
drug mechanism
hepatic porphyria
intoxication
liver
nonhuman
porphyria
rat
Animalia
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_02646021_v218_n3_p753_WainstokdeCalmanovici
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
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spelling todo:paper_02646021_v218_n3_p753_WainstokdeCalmanovici2023-10-03T15:12:52Z Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment Wainstok de Calmanovici, R. Del Rios de Molina, C.M. Taira de Yamasato, M.C. hexachlorobenzene liver enzyme phenobarbital animal experiment drug intoxication drug mechanism hepatic porphyria intoxication liver nonhuman porphyria rat Animalia The effect of a pretreatment with phenobarbitone (PB) on the porphyrinogenic action exerted by hexachlorobenzene (HCB) was examined in female rats. Kinetic studies of enzyme function after HCB poisoning showed that porphyrinogen carboxy-lyase was the only enzyme of haem biosynthesis that markedly lowered its activity. Both stages of uroporphyrinogen (UPG) III decarboxylation were decreased. This enzyme, together with UPG I synthase (increased levels) were the first enzymes altered. Subsequently, an increase in δ-aminolaevulinate (AmLev) synthase and ferrochelatase was detected; AmLev dehydratase was the last to increase. On long-term exposure, PB alone did not modify the basal values of haem intermediates; only the content of cytochrome P-450 increased. All the enzyme activities studied showed no significant changes, except ferrochelatase, which increased. With both drugs the metabolic impairment promoted by HCB was accelerated and enhanced by prior PB treatment, leading to the onset of an earlier and stronger porphyria. A more noticeable accumulation and excretion of higher carboxylated porphyrins and precursors was more promptly observed as a consequence of the early porphyrinogen carboxy-lyase blockade and the concomitant induction of AmLev synthase. Although the enzymic activities of both AmLev dehydratase and ferrochelatase were enhanced, this response differed in time. For UPG I synthase this pretreatment elicited lower values than those found in the HCB group. Cytochrome P-450 contents were immediately and slightly enhanced by all the drugs, but the values for the combined treatment were the lowest. Of the several hypotheses that could explain the action of HCB on the haem pathway, our results would suggest that the porphyrinogenic action of HCB is mediated by some of its metabolic products. Fil:Wainstok de Calmanovici, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Del Rios de Molina, C.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Taira de Yamasato, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02646021_v218_n3_p753_WainstokdeCalmanovici
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic hexachlorobenzene
liver enzyme
phenobarbital
animal experiment
drug intoxication
drug mechanism
hepatic porphyria
intoxication
liver
nonhuman
porphyria
rat
Animalia
spellingShingle hexachlorobenzene
liver enzyme
phenobarbital
animal experiment
drug intoxication
drug mechanism
hepatic porphyria
intoxication
liver
nonhuman
porphyria
rat
Animalia
Wainstok de Calmanovici, R.
Del Rios de Molina, C.M.
Taira de Yamasato, M.C.
Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment
topic_facet hexachlorobenzene
liver enzyme
phenobarbital
animal experiment
drug intoxication
drug mechanism
hepatic porphyria
intoxication
liver
nonhuman
porphyria
rat
Animalia
description The effect of a pretreatment with phenobarbitone (PB) on the porphyrinogenic action exerted by hexachlorobenzene (HCB) was examined in female rats. Kinetic studies of enzyme function after HCB poisoning showed that porphyrinogen carboxy-lyase was the only enzyme of haem biosynthesis that markedly lowered its activity. Both stages of uroporphyrinogen (UPG) III decarboxylation were decreased. This enzyme, together with UPG I synthase (increased levels) were the first enzymes altered. Subsequently, an increase in δ-aminolaevulinate (AmLev) synthase and ferrochelatase was detected; AmLev dehydratase was the last to increase. On long-term exposure, PB alone did not modify the basal values of haem intermediates; only the content of cytochrome P-450 increased. All the enzyme activities studied showed no significant changes, except ferrochelatase, which increased. With both drugs the metabolic impairment promoted by HCB was accelerated and enhanced by prior PB treatment, leading to the onset of an earlier and stronger porphyria. A more noticeable accumulation and excretion of higher carboxylated porphyrins and precursors was more promptly observed as a consequence of the early porphyrinogen carboxy-lyase blockade and the concomitant induction of AmLev synthase. Although the enzymic activities of both AmLev dehydratase and ferrochelatase were enhanced, this response differed in time. For UPG I synthase this pretreatment elicited lower values than those found in the HCB group. Cytochrome P-450 contents were immediately and slightly enhanced by all the drugs, but the values for the combined treatment were the lowest. Of the several hypotheses that could explain the action of HCB on the haem pathway, our results would suggest that the porphyrinogenic action of HCB is mediated by some of its metabolic products.
format JOUR
author Wainstok de Calmanovici, R.
Del Rios de Molina, C.M.
Taira de Yamasato, M.C.
author_facet Wainstok de Calmanovici, R.
Del Rios de Molina, C.M.
Taira de Yamasato, M.C.
author_sort Wainstok de Calmanovici, R.
title Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment
title_short Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment
title_full Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment
title_fullStr Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment
title_full_unstemmed Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment
title_sort mechanism of hexachlorobenzene-induced porphyria in rats. effect of phenobarbitone pretreatment
url http://hdl.handle.net/20.500.12110/paper_02646021_v218_n3_p753_WainstokdeCalmanovici
work_keys_str_mv AT wainstokdecalmanovicir mechanismofhexachlorobenzeneinducedporphyriainratseffectofphenobarbitonepretreatment
AT delriosdemolinacm mechanismofhexachlorobenzeneinducedporphyriainratseffectofphenobarbitonepretreatment
AT tairadeyamasatomc mechanismofhexachlorobenzeneinducedporphyriainratseffectofphenobarbitonepretreatment
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