Artículo

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" (2005) Toxicology and Applied Pharmacology. 204(2):187-195
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Abstract:

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.

Registro:

Documento: Artículo
Título:Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment
Autor:Billi De Catabbi, S.C.; Faletti, A.; Fuentes, F.; San Martín De Viale, L.C.; Cochón, A.C.
Filiación:Fac. de Ciencias Exactas Y Naturales, Depto. de Quím. Biol., Ciudad Universitaria, 1428 Buenos Aires, Argentina
Ctro. Estud. Farmacologicos B., 1414 Buenos Aires, Argentina
Fac. de Ciencias Exactas Y Naturales, Depto. de Quím. Biol., Pabellón II, 1428 Buenos Aires, Argentina
Palabras clave: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
Año:2005
Volumen:204
Número:2
Página de inicio:187
Página de fin:195
DOI: http://dx.doi.org/10.1016/j.taap.2004.09.001
Título revista:Toxicology and Applied Pharmacology
Título revista abreviado:Toxicol. Appl. Pharmacol.
ISSN:0041008X
CODEN:TXAPA
CAS:aminopyrine n demethylase, 9037-69-8; arachidonic acid, 506-32-1, 6610-25-9, 7771-44-0; cytochrome P450, 9035-51-2; ethoxyresorufin deethylase, 59793-97-4; hexachlorobenzene, 118-74-1, 55600-34-5; phospholipase A2, 9001-84-7; prostaglandin E, 11042-70-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0041008X_v204_n2_p187_BilliDeCatabbi

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Citas:

---------- APA ----------
Billi De Catabbi, S.C., Faletti, A., Fuentes, F., San Martín De Viale, L.C. & Cochón, A.C. (2005) . Hepatic arachidonic acid metabolism is disrupted after hexachlorobenzene treatment. Toxicology and Applied Pharmacology, 204(2), 187-195.
http://dx.doi.org/10.1016/j.taap.2004.09.001
---------- CHICAGO ----------
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" . Toxicology and Applied Pharmacology 204, no. 2 (2005) : 187-195.
http://dx.doi.org/10.1016/j.taap.2004.09.001
---------- MLA ----------
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" . Toxicology and Applied Pharmacology, vol. 204, no. 2, 2005, pp. 187-195.
http://dx.doi.org/10.1016/j.taap.2004.09.001
---------- VANCOUVER ----------
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. Toxicol. Appl. Pharmacol. 2005;204(2):187-195.
http://dx.doi.org/10.1016/j.taap.2004.09.001