title: The potential toxicological insights about the anti-HIV drug azidothymidine-derived monoselenides in human leukocytes: Toxicological insights of new selenium-azidothymidine analogs.
abstract: Acquired immunodeficiency syndrome (AIDS) is a worldwide disease characterized by impairments of immune function. AIDS can be associated with oxidative stress (OS) that can be linked to selenium (Se) deficiency. Se is fundamental for the synthesis of selenoproteins, such as glutathione peroxidase and thioredoxin reductase. These enzymes catalyze the decomposition of reactive oxygen species and contribute to maintain equilibrium in cell redox status. Literature data indicate that organoselenium compounds, such as ebselen and diphenyl diselenide, have antioxidant properties in vitro and in vivo models associated with OS. Nevertheless, selenocompounds can also react and oxidize thiols groups, inducing toxicity in mammals. Here, we tested the potential cytotoxic and genotoxic properties of six analogs of the prototypal anti-HIV drug azidothymidine (AZT) containing Se (5'-Se-(phenyl)zidovudine; 5'-Se-(1,3,5-trimethylphenyl)zidovudine; 5'-Se-(1-naphtyl)zidovudine; 5'-Se-(4-chlorophenyl)zidovudine) (C4); 5'-Se-(4-methylphenyl)zidovudine (C5); and 5'-(4-methylbenzoselenoate)zidovudine). C5 increased the rate of dithiothreitol oxidation (thiol oxidase activity) and C2-C4 and C6 (at 100 µM) increased DNA damage index (DI) in human leukocytes. Moreover, C5 (200 µM) decreased human leukocyte viability to about 50%. Taken together, these results indicated the low in vitro toxicity in human leukocytes of some Se-containing analogs of AZT.
authors: 1 Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: Doc
authors: D
authors: Mariano
authors: 1 Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: D
authors: D
authors: de Souza
authors: 1 Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: D F
authors: DF
authors: Meinerz
authors: 1 Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: J
authors: J
authors: Allebrandt
authors: 2 Departamento de Bioquímica, Universidade Federal de Santa Catarina, Santa Catarina, Brazil.
authors: A F
authors: AF
authors: de Bem
authors: 1 Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: W
authors: W
authors: Hassan
authors: 3 Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: Oed
authors: O
authors: Rodrigues
authors: 1 Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: Jbt
authors: J
authors: da Rocha
mesh_terms: D019380:Anti-HIV Agents / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D016566:Organoselenium Compounds / Q000633:toxicity*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000633:toxicity*
chemical_list: D019380:Anti-HIV Agents; D016566:Organoselenium Compounds; D015215:Zidovudine
keywords: AZT; DNA damage; Organoselenium compounds; cell viability; thiol oxidation