Methyl phenyl selenide causes heme biosynthesis impairment and its toxicity is not modified by dimethyl sulphoxide in vivo.

Abstract:

:Organoselenium compounds can cause anemia in mice, possibly as a consequence of impairment of the heme biosynthesis pathway. Such compounds can inhibit the sulfhydryl-containing enzyme delta-aminolevulinate dehydratase (delta-ALA-D), which is involved in the heme biosynthetic pathway, leading to a decrease in the syntheses of hemoglobin, cytochromes and other heme-proteins. Methyl phenyl selenide (CH3SePh) has chemopreventive activity against cancer in rodents, raising the possibility of therapeutic use of this compound by humans. Treatment with methyl phenyl selenide (500 micromol/kg/day, 30 days) inhibited the delta-aminolevulinate dehydratase activity in adult male mice. Furthermore, the exposure to methyl phenyl selenide caused an increase in the liver/body weight ratio and a decrease in the hemoglobin content when compared to the control animals. The vehicle used (DMSO or corn oil) did not affect any of the analyzed parameters or the selenide effects towards these parameters. In summary, results presented here support that delta-aminolevulinate dehydratase is a potential target to CH3SePh, leading to an impairment of hemoglobin content, a heme biosynthetic endpoint.

journal_name

Drug Chem Toxicol

authors

Folmer V,Farina M,Maciel EN,Nogueira CW,Zeni G,Emanuelli T,Rocha JB

doi

10.1081/dct-200039720

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

331-40

issue

4

eissn

0148-0545

issn

1525-6014

journal_volume

27

pub_type

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