Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment
Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA)...
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todo:paper_0041008X_v204_n2_p187_BilliDeCatabbi2023-10-03T14:51:15Z Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment Billi De Catabbi, S.C. Faletti, A. Fuentes, F. San Martín De Viale, L.C. Cochón, A.C. Arachidonic acid Cytochrome P450 Cytosolic phospholipase A2 Hexachlorobenzene Prostaglandin Rat liver aminopyrine n demethylase arachidonic acid cytochrome P450 ethoxyresorufin deethylase hexachlorobenzene phospholipase A2 prostaglandin E animal experiment animal model animal tissue arachidonic acid metabolism article clinical feature controlled study cytokine release enzyme activity female liver liver microsome liver toxicity membrane fluidity nonhuman porphyria cutanea tarda protein function rat statistical significance Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A2 (cPLA2) activity were investigated in an experimental model of porphyria cutanea tarda induced by HCB. Female Wistar rats were treated with a single daily dose of HCB (100 mg kg-1 body weight) for 5 days and were sacrificed 3, 10, 17, and 52 days after the last dose. HCB treatment induced the accumulation of hepatic porhyrins from day 17 and increased the activities of liver ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine N-demethylase (APND) from day 3 after the last dose. Liver microsomes from control and HCB-treated rats generated, in the presence of NADPH, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 11,12-Di HETE, and ω-OH/ω-1-OH AA. HCB treatment caused an increase in total NADPH CYP-dependent AA metabolism, with a higher response at 3 days after the last HCB dose than at the other time points studied. In addition, HCB treatment markedly enhanced PGE production and release in liver slices. This HCB effect was time dependent and reached its highest level after 10 days. At this time cPLA2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA2 activity on the 17th and 52nd day. Our results demonstrated for the first time that HCB induces both the cyclooxygenase and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were previous to the onset of a marked porphyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Observations also suggested that a possible role of cPLA2 in the early increase of AA metabolism cannot be excluded. However, the existence of other pathway(s) for metabolizable AA generation different from cPLA2 activation is also proposed. © 2004 Elsevier Inc. All rights reserved. Fil:Billi De Catabbi, S.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Faletti, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:San Martín De Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cochón, A.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_0041008X_v204_n2_p187_BilliDeCatabbi |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Arachidonic acid Cytochrome P450 Cytosolic phospholipase A2 Hexachlorobenzene Prostaglandin Rat liver aminopyrine n demethylase arachidonic acid cytochrome P450 ethoxyresorufin deethylase hexachlorobenzene phospholipase A2 prostaglandin E animal experiment animal model animal tissue arachidonic acid metabolism article clinical feature controlled study cytokine release enzyme activity female liver liver microsome liver toxicity membrane fluidity nonhuman porphyria cutanea tarda protein function rat statistical significance |
| spellingShingle |
Arachidonic acid Cytochrome P450 Cytosolic phospholipase A2 Hexachlorobenzene Prostaglandin Rat liver aminopyrine n demethylase arachidonic acid cytochrome P450 ethoxyresorufin deethylase hexachlorobenzene phospholipase A2 prostaglandin E animal experiment animal model animal tissue arachidonic acid metabolism article clinical feature controlled study cytokine release enzyme activity female liver liver microsome liver toxicity membrane fluidity nonhuman porphyria cutanea tarda protein function rat statistical significance Billi De Catabbi, S.C. Faletti, A. Fuentes, F. San Martín De Viale, L.C. Cochón, A.C. Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment |
| topic_facet |
Arachidonic acid Cytochrome P450 Cytosolic phospholipase A2 Hexachlorobenzene Prostaglandin Rat liver aminopyrine n demethylase arachidonic acid cytochrome P450 ethoxyresorufin deethylase hexachlorobenzene phospholipase A2 prostaglandin E animal experiment animal model animal tissue arachidonic acid metabolism article clinical feature controlled study cytokine release enzyme activity female liver liver microsome liver toxicity membrane fluidity nonhuman porphyria cutanea tarda protein function rat statistical significance |
| description |
Hexaclorobenzene (HCB), one of the most persistent environmental pollutants, can cause a wide range of toxic effects including cancer in animals, and hepatotoxicity and porphyria both in humans and animals. In the present study, liver microsomal cytochrome P450 (CYP)-dependent arachidonic acid (AA) metabolism, hepatic PGE production, and cytosolic phospholipase A2 (cPLA2) activity were investigated in an experimental model of porphyria cutanea tarda induced by HCB. Female Wistar rats were treated with a single daily dose of HCB (100 mg kg-1 body weight) for 5 days and were sacrificed 3, 10, 17, and 52 days after the last dose. HCB treatment induced the accumulation of hepatic porhyrins from day 17 and increased the activities of liver ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and aminopyrine N-demethylase (APND) from day 3 after the last dose. Liver microsomes from control and HCB-treated rats generated, in the presence of NADPH, hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), 11,12-Di HETE, and ω-OH/ω-1-OH AA. HCB treatment caused an increase in total NADPH CYP-dependent AA metabolism, with a higher response at 3 days after the last HCB dose than at the other time points studied. In addition, HCB treatment markedly enhanced PGE production and release in liver slices. This HCB effect was time dependent and reached its highest level after 10 days. At this time cPLA2 activity was shown to be increased. Unexpectedly, HCB produced a significant decrease in cPLA2 activity on the 17th and 52nd day. Our results demonstrated for the first time that HCB induces both the cyclooxygenase and CYP-dependent AA metabolism. The effects of HCB on AA metabolism were previous to the onset of a marked porphyria and might contribute to different aspects of HCB-induced liver toxicity such as alterations of membrane fluidity and membrane-bound protein function. Observations also suggested that a possible role of cPLA2 in the early increase of AA metabolism cannot be excluded. However, the existence of other pathway(s) for metabolizable AA generation different from cPLA2 activation is also proposed. © 2004 Elsevier Inc. All rights reserved. |
| format |
JOUR |
| author |
Billi De Catabbi, S.C. Faletti, A. Fuentes, F. San Martín De Viale, L.C. Cochón, A.C. |
| author_facet |
Billi De Catabbi, S.C. Faletti, A. Fuentes, F. San Martín De Viale, L.C. Cochón, A.C. |
| author_sort |
Billi De Catabbi, S.C. |
| title |
Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment |
| title_short |
Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment |
| title_full |
Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment |
| title_fullStr |
Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment |
| title_full_unstemmed |
Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment |
| title_sort |
hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment |
| url |
http://hdl.handle.net/20.500.12110/paper_0041008X_v204_n2_p187_BilliDeCatabbi |
| work_keys_str_mv |
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