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Abstract:

These studies try to elucidate why isocoproporphyrin appears in hexachlorobenzene-poisoned rats' feces. Chronic exposure of hexachlorobenzene to rats produces an experimental model for human porphyria cutanea tarda. After 8 weeks of treatment, rats showed high porphyrin excreta and 50% inhibition of liver uroporphyrinogen decarboxylase activity. Uroporphyrin plus heptacarboxylic porphyrin exceeded coproporphyrin in urine, whereas in feces, isocoproporphyrin, from abnormal pentacarboxylic porphyrinogen III oxidative decarboxylation by liver coproporphyrinogen oxidase, became the main porphyrin. Trypsin-treated mitochondria showed that the outer and inner membrane permeability barrier was highly conserved after hexachlorobenzene intoxication. In digitonin-treated hexachlorobenzene mitochondria, coproporphyrinogen oxidase was free in the mitochondrial intermembrane space, whereas in normal mitochondria, 30% to 50% remained anchored to the inner membrane. Hexachlorobenzene led to a decrease in respiratory control and ADP/O ratios (uncoupled mitochondria). Albumin restored oxidative phosphorylation, indicating no irreversible inner membrane damage. Normal and hexachlorobenzene mitochondria oscillatory studies exhibited similar damping factor values, showing that hexachlorobenzene had no significant effect on membrane fluidity and elasticity. Mitochondrial uncoupling could explain the free state of the enzyme within the intermembrane space. The free state of the enzyme makes it more flexible and would allow pentacarboxylic porphyrinogen III, whose levels are increased, to compete with coproporphyrinogen III and being transformed into dehydroisocoproporphyrinogen, the liver forerunner of fecal isocoproporphyrin. © American College of Toxicology.

Registro:

Documento: Artículo
Título:Hexachlorobenzene treatment on hepatic mitochondrial function parameters and intracellular coproporphyrinogen oxidase location
Autor:Sopena, Y.E.; Ferramola De Sancovich, A.M.; Sancovich, H.A.
Filiación:Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina
Palabras clave:Coproporphyrinogen Oxidase; Experimental Porphyria; Hexachlorobenzene; Isocoproporphyrin; Mitochondria; adenosine diphosphate; albumin; coproporphyrin; coproporphyrinogen oxidase; digitonin; heptacarboxyporphyrin; hexachlorobenzene; isocoproporphyrin; oxygen; pentacarboxylic porphyrinogen III; porphyrin derivative; porphyrinogen; trypsin; unclassified drug; uroporphyrin; uroporphyrinogen decarboxylase; coproporphyrinogen oxidase; digitonin; porphyrin; trypsin; animal experiment; animal tissue; article; cellular distribution; controlled study; decarboxylation; disease model; elasticity; enzyme activity; enzyme inhibition; feces; female; liver mitochondrion; long term exposure; membrane damage; membrane fluidity; membrane permeability; nonhuman; oscillation; outer membrane; oxidative phosphorylation; permeability barrier; porphyria cutanea tarda; rat; respiration control; urine; animal; drug effect; metabolism; physiology; Wistar rat; Rattus; Animals; Coproporphyrinogen Oxidase; Digitonin; Feces; Female; Hexachlorobenzene; Mitochondria, Liver; Porphyrins; Rats; Rats, Wistar; Trypsin
Año:2008
Volumen:27
Número:6
Página de inicio:455
Página de fin:465
DOI: http://dx.doi.org/10.1080/10915810802657002
Título revista:International Journal of Toxicology
Título revista abreviado:Int. J. Toxicol.
ISSN:10915818
CODEN:IJTOF
CAS:adenosine diphosphate, 20398-34-9, 58-64-0; coproporphyrin, 27121-71-7; coproporphyrinogen oxidase, 9076-84-0; digitonin, 11024-24-1; heptacarboxyporphyrin, 25744-38-1; hexachlorobenzene, 118-74-1, 55600-34-5; isocoproporphyrin, 36548-09-1; oxygen, 7782-44-7; porphyrinogen, 4396-11-6; trypsin, 9002-07-7; uroporphyrin, 18273-06-8, 26316-36-9, 553-18-4, 607-14-7; uroporphyrinogen decarboxylase, 9024-70-8; porphyrin, 24869-67-8; Coproporphyrinogen Oxidase, 1.3.3.3; Digitonin, 11024-24-1; Hexachlorobenzene, 118-74-1; Porphyrins; Trypsin, 3.4.21.4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10915818_v27_n6_p455_Sopena

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Citas:

---------- APA ----------
Sopena, Y.E., Ferramola De Sancovich, A.M. & Sancovich, H.A. (2008) . Hexachlorobenzene treatment on hepatic mitochondrial function parameters and intracellular coproporphyrinogen oxidase location. International Journal of Toxicology, 27(6), 455-465.
http://dx.doi.org/10.1080/10915810802657002
---------- CHICAGO ----------
Sopena, Y.E., Ferramola De Sancovich, A.M., Sancovich, H.A. "Hexachlorobenzene treatment on hepatic mitochondrial function parameters and intracellular coproporphyrinogen oxidase location" . International Journal of Toxicology 27, no. 6 (2008) : 455-465.
http://dx.doi.org/10.1080/10915810802657002
---------- MLA ----------
Sopena, Y.E., Ferramola De Sancovich, A.M., Sancovich, H.A. "Hexachlorobenzene treatment on hepatic mitochondrial function parameters and intracellular coproporphyrinogen oxidase location" . International Journal of Toxicology, vol. 27, no. 6, 2008, pp. 455-465.
http://dx.doi.org/10.1080/10915810802657002
---------- VANCOUVER ----------
Sopena, Y.E., Ferramola De Sancovich, A.M., Sancovich, H.A. Hexachlorobenzene treatment on hepatic mitochondrial function parameters and intracellular coproporphyrinogen oxidase location. Int. J. Toxicol. 2008;27(6):455-465.
http://dx.doi.org/10.1080/10915810802657002