title: 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.
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brasil. vandfolmer@yahoo.com.br
authors.forename: Vanderlei
authors.initials: V
authors.lastname: Folmer
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farina
authors.forename: Evelise N
authors.initials: EN
authors.lastname: Maciel
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: Gilson
authors.initials: G
authors.lastname: Zeni
authors.forename: Tatiana
authors.initials: T
authors.lastname: Emanuelli
authors.forename: João B T
authors.initials: JB
authors.lastname: Rocha
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006418:Heme / Q000096:biosynthesis*; D006454:Hemoglobins / Q000032:analysis; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D006454:Hemoglobins; D016566:Organoselenium Compounds; C497779:methyl phenyl selenide; D006418:Heme; D000623:Porphobilinogen Synthase; D004121:Dimethyl Sulfoxide