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Time-dependent porphyric response in mice subchronically exposed to arsenic

Sección de Toxicología Ambiental, Departamento de Farmacología y Toxicologia, CINVESTAV-IPN, PO Box 14-740, México, D.F. 07000, México, MRC Toxicology Unit, Hodkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK

ME Cebrián

Sección de Toxicología Ambiental, Departamento de Farmacología y Toxicologia, CINVESTAV-IPN, PO Box 14-740, México, D.F. 07000, México

A. Albores

Sección de Toxicología Ambiental, Departamento de Farmacología y Toxicologia, CINVESTAV-IPN, PO Box 14-740, México, D.F. 07000, México

CK Lim

MRC Toxicology Unit, Hodkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK

Francesco De Matteis

MRC Toxicology Unit, Hodkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK

1 A time-course study was carried out in mice subchroni cally 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), uropor phyrinogen decarboxylase (URO-D) and coproporphyrino gen oxidase (COPRO-O), as well as to the hepatic por phyrin 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) corre sponded 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 subchroni cally exposed to As. Finally, the relative magnitudes of URO-D and COPRO-O inhibitions may determine the pat tern of porphyrin concentration observed in urine and tis sues.

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 uri nary porphyrin profiles found in both species. The possi ble reasons for the similarities and differences are briefly discussed.

Key Words: mice • arsenic • porphyrin excretion • renal enzymes • hepatic enzymes

Human & Experimental Toxicology, Vol. 14, No. 6, 475-483 (1995)
DOI: 10.1177/096032719501400602


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