CEQUINOR   05415
CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Unidad Ejecutora - UE
artículos
Título:
Hydroxylamido/ amino acid complexes of oxovanadium(V). Toxicological study in cell culture and in a zebrafish model.
Autor/es:
LEÓN IE; DI BIRGILIO AL; BARRIO DA; ARRAMBIDE G; GAMBINO D; ETCHEVERRY SB
Revista:
METALLOMICS
Editorial:
ROYAL SOC CHEMISTRY
Referencias:
Lugar: CAMBRIDGE; Año: 2012 vol. 4 p. 1287 - 1287
ISSN:
1756-5901
Resumen:
<!-- /* Font Definitions */ @font-face {font-family:AdvTimes; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:auto; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:3 0 0 0 1 0;} @font-face {font-family:AdvTimes-i; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-alt:"Arial Unicode MS"; mso-font-charset:128; mso-generic-font-family:auto; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:0 134676480 16 0 131072 0;} @font-face {font-family:AdvPi1; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:roman; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:3 0 0 0 1 0;} @font-face {font-family:AdvEls-ent4; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:3 0 0 0 1 0;} @font-face {font-family:Calibri; mso-font-alt:Arial; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:-520092929 1073786111 9 0 415 0;} @font-face {font-family:"@AdvTimes-i"; panose-1:0 0 0 0 0 0 0 0 0 0; mso-font-charset:128; mso-generic-font-family:auto; mso-font-format:other; mso-font-pitch:auto; mso-font-signature:0 134676480 16 0 131072 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin-top:0cm; margin-right:0cm; margin-bottom:10.0pt; margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri; mso-fareast-font-family:Calibri; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:ES-AR; mso-fareast-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Oxovanadium(V) complexes [VO(NH2O)2(val)] and [VO(NH2O)2(met)] caused inhibition of cell proliferation in two osteoblast cell lines, MC3T3-E1 and UMR106, as well as the viability of zebrafish eggs. In MC3T3-E1, both compounds inhibited cell proliferation (up to ca. 40% at 25 mM [VO(NH2O)2(val)] and 25% at 25 mM [VO(NH2O)2(met)]). This effect occurs in a dose response manner from 2.5 mM (p o 0.01) with a more deleterious action of [VO(NH2O)2(met)]. In UMR106 tumoral cells, [VO(NH2O)2(val)] inhibited cell proliferation up to 75% from 25 mM while [VO(NH2O)2(met)] behaved as an inhibitory agent in the whole range of concentrations (p o 0.01). Similar toxic effects were obtained from morphological studies in cell cultures. Moreover, the IC50 values for both complexes in culture studies correlated with the IC50 values obtained with an in vivo model of toxicity (FET test). Besides, the cytotoxicity evaluation in cell culture showed a decrease in mitochondrial activity which was stronger for [VO(NH2O)2(met)] than for [VO(NH2O)2(val)] (44% vs. 58% at 25 mM) in both cell lines (p o 0.001). Genotoxicity assessed by micronuclei induction also showed a stronger effect of [VO(NH2O)2(met)] in both cell lines. Besides, [VO(NH2O)2(val)] caused DNA damage determined by comet formation in MC3T3-E1 cells in the range of 2.5–25 mM, while this effect could not be observed in the osteosarcoma cells. On the other hand, [VO(NH2O)2(val)] enhanced ROS levels over basal up to 225% and 170% at 100 mM in MC3T3-E1 and UMR106 cells, respectively (p o 0.01). For [VO(NH2O)2(met)] a similar situation was observed, suggesting an important role for oxidative stress in the toxicity mechanism of action. Although both complexes showed interesting results that would deserve further drug development [VO(NH2O)2(val)] was more stable than [VO(NH2O)2(met)] in the solid state. Therefore, we consider that [VO(NH2O)2(val)] is a good candidate to be tested in in vivo models as a potential antitumoral agent. <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} -->
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