Assessment of arsenic effects on cytosolic heme status using tryptophan pyrrolase as an index.
Acute arsenic (As) administration produced in rat liver a decrease in the heme saturation of tryptophan pyrrolase (TP), accompanied by dose-related increases in 5-aminolevulinate synthetase (ALAS) and heme oxygenase (HO) activities, along with a corresponding decrease in cytochrome P-450 (P-450) concentration. The relationship between heme synthesis and degradation was altered as a result of As treatment. The magnitude of these effects was related to the oxidation state of arsenic, sodium arsenite (AsIII) being more potent than sodium arsenate (AsV). These results support the contention that the heme saturation of TP is sensitive to treatments that modify liver heme concentration. The increase in HO activity produced by As appears to be mediated by a mechanism largely or entirely independent of heme. The main effects of continuous exposure to AsIII were an initial decrease in the heme saturation of TP, which remained constant during the period of treatment, and an initial increase in ALAS activity, which after ten days of exposure dropped somewhat but remained above control values. No significant effects on HO or P-450 concentration were observed. These results were interpreted as indicative that a new balance between heme synthesis and degradation had been reached and that an adaptive response to the subchronic effects of AsIII was taking place.
Cebrián
M E
ME
Robens Institute, University of Surrey, Guildford, UK.
Albores
A
A
Connelly
J C
JC
Bridges
J W
JW
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D001149:Arsenates / Q000633:toxicity*; D001151:Arsenic / Q000633:toxicity*; D018053:Arsenites; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D001149:Arsenates; D018053:Arsenites; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D014366:Tryptophan Oxygenase; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase; C015001:arsenite; D001151:Arsenic; C025657:arsenic acid