info:eu-repo/semantics/article
Nitrosative stress and apoptosis by intravenous ferumoxytol, iron isomaltoside 1000, iron dextran, iron sucrose, and ferric carboxymaltose in a nonclinical model
Registro en:
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Giani, Jorge Fernando; Dominici, Fernando Pablo; Angerosa, Margarita; Nitrosative stress and apoptosis by intravenous ferumoxytol, iron isomaltoside 1000, iron dextran, iron sucrose, and ferric carboxymaltose in a nonclinical model; Georg Thieme Verlag Kg; Drug Research; 65; 7; 7-2014; 354-360
2194-9379
Autor
Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Giani, Jorge Fernando
Dominici, Fernando Pablo
Angerosa, Margarita
Resumen
Iron is involved in the formation as well as in the scavenging of reactive oxygen and nitrogen species. Thus, iron can induce as well as inhibit both oxidative and nitrosative stress. It also has a key role in reactive oxygen and nitrogen species-mediated apoptosis. We assessed the differences in tyrosine nitration and caspase 3 expression in the liver, heart, and kidneys of rats treated weekly with intravenous ferumoxytol, iron isomaltoside 1000, iron dextran, iron sucrose and ferric carboxymaltose (40 mg iron/kg body weight) for 5 weeks. Nitrotyrosine was quantified in tissue homogenates by Western blotting and the distribution of nitrotyrosine and caspase 3 was assessed in tissue sections by immunohistochemistry. Ferric carboxymaltose and iron sucrose administration did not result in detectable levels of nitrotyrosine or significant levels of caspase 3 vs. control in any of the tissue studied. Nitrotyrosine and caspase 3 levels were significantly (p<0.01) increased in all assessed organs of animals treated with iron dextran and iron isomaltoside 1000, as well as in the liver and kidneys of ferumoxytol-treated animals compared to isotonic saline solution (control). Nitrotyrosine and caspase 3 levels were shown to correlate positively with the amount of Prussian blue-detectable iron(III) deposits in iron dextran- and iron isomaltoside 1000-treated rats but not in ferumoxytol-treated rats, suggesting that iron dextran, iron isomaltoside 1000 and ferumoxytol induce nitrosative (and oxidative) stress as well as apoptosis via different mechanism(s). Fil: Toblli, Jorge Eduardo. Universidad de Buenos Aires; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cao, Gabriel Fernando. Universidad de Buenos Aires; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina Fil: Giani, Jorge Fernando. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisico-Química Biológicas; Argentina Fil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisico-Química Biológicas; Argentina Fil: Angerosa, Margarita. Universidad de Buenos Aires; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina