Organochalcogens effects on delta-aminolevulinate dehydratase activity from human erythrocytic cells in vitro.
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.
Nogueira
C W
CW
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
Borges
V C
VC
Zeni
G
G
Rocha
J B T
JB
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
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