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Some hepatic and extrahepatic effects of arsenic and selenium on heme metabolism.

Cebrian-Garcia, Mariano Enrique. (1986) Some hepatic and extrahepatic effects of arsenic and selenium on heme metabolism. Doctoral thesis, University of Surrey (United Kingdom)..

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The acute administration of AsIII or AsV to rats produced in liver a decrease in the heme saturation of tryptophan pyrrolase (TP) accompanied by dose-related increases in aminolevulinate synthetase (ALAS) and heme oxygenase (HO) activities and corresponding decreases in P-450 concentration. The relationship between heme synthesis and degradation was changed as a result of As treatment. The magnitude of these effects was related to the oxidation state of As, AsIII being more potent than AsV. These results support the contention that the heme saturation of TP is sensitive to treatments that modify liver heme concentration. However, it remains to be stablished which parameter, heme saturation of TP or ALA synthetase activity reflect more accurately changes in the "free heme" pool size. The increase in heme oxygenase produced by As in liver appears to be mediated by a mechanism largely or entirely independent of heme. There were indications that the inhibition of P-450- dependent monooxygenases reflects a selective effect of As on certain P-450 isoforms. Although only the higher doses of As were able to affect testicular heme metabolism, the general effect was similar to that observed in liver. AsV affected renal ALAS, HO and P-450 at doses which were ineffective in liver and testis. The main effects of continuous exposure to As III were : 1) an initial decrease in the degree of heme saturation of TP which remained constant during the period of treatment and 2) an initial increase in ALA synthetase which after 10 days of exposure was reduced to a 30% increase. No significant effects on heme oxygenase or P-450 concentration were observed. These observations were interpreted as indicative that a new balance between heme synthesis and degradation had been reached and that an adaptive response to the toxic effects of AsIII was taking place. Se produced effects on TP, ALAS and HO similar to those produced by As, but it was more potent than either AsIII or AsV. Se appears to be unusual in that it increases HO without reducing P-450 concentration. Se also appears to be the first element reported to increase epoxide hydrolase (EH) activity, as yet there is no evidence to explain how or why Se induces EH. It appears that Se has a dual effect on As-induced hepatoxicity. On the one hand it has additive effects in reducing the heme saturation of TP, and on the other it seems to protect against the decrease in P-450 levels produced by AsIII.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
Cebrian-Garcia, Mariano Enrique.
Date : 1986
Contributors :
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1986.
Depositing User : EPrints Services
Date Deposited : 22 Jun 2018 13:01
Last Modified : 06 Nov 2018 16:52

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