Hemolytic and genotoxic evaluation of organochalcogens in human blood cells in vitro.
This study investigated the hemolytic and genotoxic effect of different organoselenium and organotellurium compounds in human blood cells, as simple tests for screening the toxicity of organochalcogenides. For osmotic fragility (OF) test, samples of total blood were incubated with the organochalcogens at 4, 8, 50, 75 and 100 microM or vehicle (DMSO) for 90 min at 37 degrees C. The EC(50) values for hemolysis were significantly increased in erythrocytes exposed to diphenyl selenide (II), diphenyl diselenide (III), diphenyl telluride (IV), diphenyl ditelluride (V), (S)-2-amino-1-diselenide-3-methylpropanyl (IX), butyl(styryl)telluride (XIII) and 2-(butyltellurium)furan (XIV) at higher concentrations tested. The exposure of erythrocytes to organochalcogens diphenyl diselenide (II) and butyl(styryl)telluride (XIII), which had greater hemolytic effect, did not modify catalase activity, reactive oxygen species (ROS) production and -SH content. On the other hand, Na(+)/K(+) ATPase activity of erythrocyte ghosts was significantly inhibited by the compounds diphenyl diselenide (II) and butyl(styryl)telluride (XIII) (P<0.05) in a concentration-dependent manner. The inhibition of Na(+)/K(+) ATPase activity was completely reversed by dithiothreitol (DTT); indicating reaction of these organochalcogens with thiol groups of the enzyme. The thiol oxidase activity of the compounds II and XIII was supported by the fact that the rate of DTT oxidation was increased significantly by both chalcogens. In the higher concentrations, the compounds (II) and (XIII) were strongly genotoxic and cytotoxic to human leukocytes cells, as verified by the DNA damage and cell viability evaluation. Our results suggest that at relatively high concentration organochalcogenides exhibit hemolytic and genotoxic action in human blood cells, which are probably linked to their thiol oxidase activity and preferential interaction with sulfhydryl groups critical to enzymes.
Santos
D B
DB
Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Schiar
V P P
VP
Paixão
M W
MW
Meinerz
D F
DF
Nogueira
C W
CW
Aschner
M
M
Rocha
J B T
JB
Barbosa
N B V
NB
D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D009996:Osmotic Fragility / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013691:Tellurium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
D016566:Organoselenium Compounds; D013438:Sulfhydryl Compounds; D013691:Tellurium