title: Hexachlorobenzene treatment on hepatic mitochondrial function parameters and intracellular coproporphyrinogen oxidase location.
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.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 4557 (C1419HUM) CABA, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Yolanda E
authors.initials: YE
authors.lastname: Sopena
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ferramola de Sancovich
authors.forename: Horacio A
authors.initials: HA
authors.lastname: Sancovich
mesh_terms: D000818:Animals; D003304:Coproporphyrinogen Oxidase / Q000378:metabolism*; D004072:Digitonin / Q000494:pharmacology; D005243:Feces; D005260:Female; D006581:Hexachlorobenzene / Q000633:toxicity*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D011166:Porphyrins / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000494:pharmacology
chemical_list: D011166:Porphyrins; D006581:Hexachlorobenzene; D003304:Coproporphyrinogen Oxidase; D014357:Trypsin; D004072:Digitonin