Effects of the porphyrinogenic compounds hexachlorobenzene and 3,5-diethoxycarbonyl-1,4-dihydrocollidine on polyamine metabolism.
The naturally occurring polyamines--putrescine, spermidine and spermine--are organic cations present in all living cells and essential for cell growth and differentiation. The aim of the present study was to extend the investigations on the effects of porphyrinogenic compounds on polyamine metabolism. This was achieved by studying putrescine, spermidine and spermine levels in a model of acute porphyria, i.e. 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced porphyria, and in a model of non-acute porphyria, i.e. hexachlorobenzene (HCB)-induced porphyria. HCB administration to female Wistar rats for 7, 14, 21, 28 and 56 days did not alter polyamine levels in liver, even though rats presented clear signs of HCB-induced porphyria. In contrast to HCB, DDC treatment resulted in a remarkable increase in putrescine levels in the liver of female and male Sprague-Dawley rats. This increase was due, at least in part, to ornithine decarboxylase (ODC) activation. DDC induction of putrescine levels did not show organ specificity, since it could also be seen in adrenal gland. Interestingly, the deregulation of polyamine biosynthesis occurred concomitantly with the deregulation of the heme biosynthetic pathway. In addition to porphyria, it is known that DDC intoxication affects several proteins of the hepatocyte cytoskeleton. It is suggested that DDC-induced increase in ODC activity and putrescine levels may be an early event contributing to alter the cytoskeleton.
Cochón
Adriana Cristina
AC
Laboratorio de Porfirias Experimentales y Metabolismo del Hemo, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Nuñez, 1428 Buenos Aires, Argentina.
González
Nélida
N
San Martín de Viale
Leonor Carmen
LC
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D003997:Dicarbethoxydihydrocollidine / Q000494:pharmacology*; D005260:Female; D005294:Ferrochelatase / Q000378:metabolism; D006581:Hexachlorobenzene / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011166:Porphyrins / Q000096:biosynthesis*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012727:Sex Characteristics; D014575:Uroporphyrinogen Decarboxylase / Q000378:metabolism
D015317:Biogenic Polyamines; D011166:Porphyrins; D011506:Proteins; D006581:Hexachlorobenzene; D003997:Dicarbethoxydihydrocollidine; D000624:5-Aminolevulinate Synthetase; D009955:Ornithine Decarboxylase; D014575:Uroporphyrinogen Decarboxylase; D005294:Ferrochelatase