Time-dependent porphyric response in mice subchronically exposed to arsenic.
1. A time-course study was carried out in mice subchronically exposed to As III (as sodium arsenite) or As V (as sodium arsenate), via drinking water, relating the pattern of urinary porphyrin excretion to the renal and hepatic enzyme activities of porphobilinogen deaminase (PBGD), uroporphyrinogen III synthetase (URO III-S), uroporphyrinogen decarboxylase (URO-D) and coproporphyrinogen oxidase (COPRO-O), as well as to the hepatic porphyrin accumulation in the treated animals. 2. A time-dependent, wave-like porphyric response was found in mice exposed to As V, and the increases seen in total urinary porphyrins (at 3 weeks of exposure) corresponded to an increased activity of PBGD and Uro III-S in liver. 3. Significant decreases in renal URO-D and hepatic and renal COPRO-O activities were found in treated mice; these inhibitions were more pronounced in animals exposed to As III. 4. The combination of these enzymic effects may explain the time-dependent porphyric response of mice subchronically exposed to As. Finally, the relative magnitudes of URO-D and COPRO-O inhibitions may determine the pattern of porphyrin concentration observed in urine and tissues. 5. The decrease in renal URO-D activity may help to explain the inversion in the coproporphyrin/uroporphyrin ratio previously reported in humans chronically exposed to As; however, there were differences between the urinary porphyrin profiles found in both species. The possible reasons for the similarities and differences are briefly discussed.
García-Vargas
G
G
Departamento de Farmacología y Toxicología, CINVESTAV-IPN, México, D.F., México.
Cebrián
M E
ME
Albores
A
A
Lim
C K
CK
De Matteis
F
F
D000284:Administration, Oral; D000818:Animals; D001149:Arsenates / Q000008:administration & dosage / Q000633:toxicity*; D018053:Arsenites / Q000008:administration & dosage / Q000633:toxicity*; D003304:Coproporphyrinogen Oxidase / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D011163:Hydroxymethylbilane Synthase / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011166:Porphyrins / Q000378:metabolism / Q000652:urine*; D017670:Sodium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D013439:Sulfhydryl Reagents / Q000008:administration & dosage / Q000633:toxicity*; D014575:Uroporphyrinogen Decarboxylase / Q000037:antagonists & inhibitors; D014576:Uroporphyrinogen III Synthetase / Q000037:antagonists & inhibitors
D001149:Arsenates; D018053:Arsenites; D011166:Porphyrins; D017670:Sodium Compounds; D013439:Sulfhydryl Reagents; C017947:sodium arsenite; C009277:sodium arsenate; D003304:Coproporphyrinogen Oxidase; D011163:Hydroxymethylbilane Synthase; D014575:Uroporphyrinogen Decarboxylase; D014576:Uroporphyrinogen III Synthetase