Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment
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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1984
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v218_n3_p753_WainstokdeCalmanovici http://hdl.handle.net/20.500.12110/paper_02646021_v218_n3_p753_WainstokdeCalmanovici |
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paper:paper_02646021_v218_n3_p753_WainstokdeCalmanovici2023-06-08T15:23:05Z Mechanism of hexachlorobenzene-induced porphyria in rats. Effect of phenobarbitone pretreatment Wainstok de Calmanovici, Rosa Ríos de Molina, María del Carmen Taira, María Cristina 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. 1984 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v218_n3_p753_WainstokdeCalmanovici 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, Rosa Ríos de Molina, María del Carmen Taira, María Cristina 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. |
author |
Wainstok de Calmanovici, Rosa Ríos de Molina, María del Carmen Taira, María Cristina |
author_facet |
Wainstok de Calmanovici, Rosa Ríos de Molina, María del Carmen Taira, María Cristina |
author_sort |
Wainstok de Calmanovici, Rosa |
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 |
publishDate |
1984 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02646021_v218_n3_p753_WainstokdeCalmanovici http://hdl.handle.net/20.500.12110/paper_02646021_v218_n3_p753_WainstokdeCalmanovici |
work_keys_str_mv |
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