title: Organochalcogens effects on delta-aminolevulinate dehydratase activity from human erythrocytic cells in vitro.
abstract: Organochalcogens are important intermediates and useful reagents in organic synthesis, which can increase human exposure risk to these chemicals in the workplace. As well, there are a number of reported cases of acute toxicity following organochalcogen ingestion of vitamins and dietary supplements. Since, the erythrocytic delta-ALA-D activity could be an important indicator of toxicity this report investigated the organochalcogens effects on blood delta-ALA-D in vitro. To investigate a possible involvement of cysteinyl groups in the inhibitory actions of diphenyl diselenide, diphenyl ditelluride and Ebselen (4-100 micro M), the effects of thiol reducing agents (0-3 mM) or zinc chloride (0-2 mM) were examined. Diphenyl ditelluride, diphenyl diselenide and Ebselen inhibited in a concentration-dependent manner delta-ALA-D activity from human erythrocytes. Ebselen was lesser delta-ALA-D inhibitor than (PhSe)(2) and (PhTe)(2), whereas the diorganoyldichalcogenides displayed similar inhibitory potency towards delta-ALA-D. Dithiothreitol, a hydrophobic SH-reducing agent, was able to reactivate and to protect inhibited delta-ALA-D. The pre-incubation of blood with the inhibitors changed considerably the reversing potency of thiols. From these findings we suggest that organochalcogens inactivate in vitro human erythrocyte delta-ALA-D by an interaction with the sulfhydryl group essential of the enzyme activity.
authors.affiliation: Departamento de Qui;mica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, CEP 97105-900, Santa Maria, RS, Brazil. gzeni@quimica.ufsm.br
authors.forename: C W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: V C
authors.initials: VC
authors.lastname: Borges
authors.forename: G
authors.initials: G
authors.lastname: Zeni
authors.forename: J B T
authors.initials: JB
authors.lastname: Rocha
mesh_terms: D000975:Antioxidants / Q000633:toxicity*; D001393:Azoles / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D001555:Benzene Derivatives / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D003545:Cysteine / Q000494:pharmacology; D004220:Disulfides / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D004229:Dithiothreitol / Q000494:pharmacology; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D005982:Glutathione Transferase / Q000494:pharmacology; D006801:Humans; D054833:Isoindoles; D009942:Organometallic Compounds / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001393:Azoles; D001555:Benzene Derivatives; D004220:Disulfides; D054833:Isoindoles; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; C434247:diphenylditelluride; C042986:ebselen; C053871:diphenyl disulfide; D005982:Glutathione Transferase; D000623:Porphobilinogen Synthase; D015032:Zinc; D003545:Cysteine; D004229:Dithiothreitol