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1.
Eur J Pharmacol ; 661(1-3): 92-101, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21549114

RESUMEN

Acetaminophen (APAP) hepatotoxicity has been related with several cases of cirrhosis, hepatitis and suicides attempts. Notably, oxidative stress plays a central role in the hepatic damage caused by APAP and antioxidants have been tested as alternative treatment against APAP toxicity. In the present study, we observed the hepatoprotector activity of the diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP), an organotellurium compound with low toxicity and high antioxidant potential. When the dose of 200 mg/kg of APAP was used, we observed that all used doses of DPTVP were able to restore the -SH levels that were depleted by APAP. Furthermore, the increase in thiobarbituric acid reactive substances levels and in the seric alanine aminotransferase (ALT) activity and the histopathological alterations caused by APAP were restored to control levels by DPTVP (30, 50 and 100 µmol/kg). On the other hand, when the 300 mg/kg dose of APAP was used, DPTVP restored the non-proteic -SH levels and repaired the normal liver morphology of the intoxicated mice only at 50 µmol/kg. Our in vitro results point out to a scavenging activity of DPTVP against several reactive species, action that is attributed to its chemical structure. Taken together, our results demonstrate that the pharmacological action of DPTVP as a hepatoprotector is probably due to its scavenging activity related to its chemical structure.


Asunto(s)
Acetaminofén/efectos adversos , Citoprotección/efectos de los fármacos , Depuradores de Radicales Libres/farmacología , Hígado/efectos de los fármacos , Compuestos Organometálicos/farmacología , Organofosfonatos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/metabolismo , Radicales Libres/metabolismo , Hígado/patología , Masculino , Ratones , Compuestos Organometálicos/metabolismo , Organofosfonatos/metabolismo
2.
Chem Biol Interact ; 177(2): 153-60, 2009 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-18950608

RESUMEN

Oximes are compounds generally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). The aim of this study was to examine the capacity of the butane-2,3-dionethiosemicarbazone oxime to scavenge different forms of reactive species (RS) in vitro, as well as counteract their formation. The potential antioxidant and toxic activity of the oxime was assayed both in vitro and ex vivo. The obtained results indicate a significant hydrogen peroxide (H2O2), nitric oxide (NO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity at 0.275, 0.5 and 5microM of oxime, respectively (p< or =0.05). The oxime exhibited a powerful inhibitory effect on dihydroxybenzoate formation (25microM) (p< or =0.05) and also decreased deoxyribose degradation induced by Fe2+ and via Fenton reaction (0.44 and 0.66mM, respectively) (p< or =0.05). The oxime showed a significant inhibitory effect on sigma-phenantroline reaction with Fe2+ (0.4mM) suggesting a possible interaction between the oxime and iron. A significant decrease in the basal and pro-oxidant-induced lipid peroxidation in brain, liver, and kidney of mice was observed both in vitro and ex vivo (p< or =0.05). In addition, in our ex vivo experiments the oxime did not depict any significant changes in thiol levels of liver, kidney and brain as well as did not modify the delta-aminolevulinate dehydratase (delta-ALA-D) activity in these tissues. Taken together our results indicate an in vitro and ex vivo antioxidant activity of the oxime possibly due to its scavenging activity toward different RS and a significant iron interaction.


Asunto(s)
Antioxidantes/farmacología , Depuradores de Radicales Libres/farmacología , Peroxidación de Lípido/efectos de los fármacos , Oximas/farmacología , Animales , Antioxidantes/toxicidad , Compuestos de Bifenilo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/toxicidad , Radicales Libres , Hidrazinas/metabolismo , Técnicas In Vitro , Riñón/efectos de los fármacos , Riñón/metabolismo , Dosificación Letal Mediana , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Óxido Nítrico/metabolismo , Oximas/toxicidad , Picratos , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
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