Effects of the porphyrinogenic compounds hexachlorobenzene and 3,5-diethoxycarbonyl-1,4-dihydrocollidine on polyamine metabolism

• Published in: Toxicology (Amsterdam) Vol. 176; no. 3; pp. 209 - 219
• Main Authors: COCHON, Adriana Cristina, GONZALEZ, Nélida, SAN MARTIN DE VIALE, Leonor Carmen
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15-07-2002; Amsterdam Elsevier Science
• Subjects: 3,5-Diethoxycarbonyl-1,4-dihydrocollidine; 5-Aminolevulinate Synthetase - metabolism; Animals; Biogenic Polyamines - metabolism; Biological and medical sciences; Dicarbethoxydihydrocollidine - pharmacology; Female; Ferrochelatase - metabolism; Hexachlorobenzene; Hexachlorobenzene - pharmacology; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Metabolic diseases; Ornithine decarboxylase; Ornithine Decarboxylase - metabolism; Other metabolic disorders; Pigments (porphyrias, hyperbilirubinemias...); Polyamine; Porphyrin; Porphyrins - biosynthesis; Proteins - metabolism; Putrescine; Rat; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sex Characteristics; Spermidine; Spermine; Uroporphyrinogen Decarboxylase - metabolism; ALA-S, 5-aminolaevulinate synthase; Polyamine; Rat; Ornithine decarboxylase; Putrescine; 3,5-Diethoxycarbonyl-1,4-dihydrocollidine; ODC, ornithine decarboxylase; DDC, 3,5-diethoxycarbonyl-1,4-dihydrocollidine; Spermine; TCDD, 2,3,7,8-tetrachlorodibenzo- p-dioxin; URO-D, uroporphyrinogen decarboxylase; Porphyrin; Spermidine; HCB, hexachlorobenzene; Hexachlorobenzene; Porphyria; Photosensitivity; Skin disease; Toxicity; Rodentia; Metabolic diseases; Enzymopathy; Genetic disease; Vertebrata; Experimental disease; Mammalia; Animal; Pigments
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(02)00145-2

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.