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Time-dependent porphyric response in mice subchronically exposed to arsenic.

作者信息

García-Vargas G, Cebrián M E, Albores A, Lim C K, De Matteis F

机构信息

Departamento de Farmacología y Toxicología, CINVESTAV-IPN, México, D.F., México.

出版信息

Hum Exp Toxicol. 1995 Jun;14(6):475-83. doi: 10.1177/096032719501400602.

DOI:10.1177/096032719501400602
PMID:8519522
Abstract
  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.
摘要

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