RESUMEN
The ability of the mitochondria-targeted plastoquinone derivative 10-(6'-plastoquinonyl)decyl triphenylphosphonium (SkQ(1)) to decrease ischemia-reperfusion injury in isolated liver during hypothermic storage (HS) was studied. Rat liver was stored for 24 h at 4°C without or in the presence of 1 µM SkQ(1) with following reperfusion for 60 min at 37°C. The presence in the storage medium of SkQ(1) significantly decreased spontaneous production of reactive oxygen species and intensity of lipid peroxidation in the liver during HS and reperfusion. The GSH level after HS in solution with SkQ(1) was reliably higher, but reperfusion leveled this effect. At all stages of experiment the presence of SkQ(1) did not prevent the decrease of antioxidant enzyme activities such as catalase, GSH peroxidase, GSH reductase, and glucose-6-phosphate dehydrogenase. The addition of SkQ(1) to the storage medium improved energetic function of the liver, as was revealed in increased respiratory control index of mitochondria and ATP level. SkQ(1) exhibited positive effect on the liver secretory function and morphology after HS as revealed in enhanced bile flow rate during reperfusion and partial recovery of organ architectonics and state of liver sinusoids and hepatocytes. The data point to promising application of mitochondria-targeted antioxidants for correction of the ischemia-reperfusion injury of isolated liver during long-term cold storage before transplantation.
Asunto(s)
Regulación hacia Abajo/efectos de los fármacos , Hígado/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Plastoquinona/análogos & derivados , Daño por Reperfusión/tratamiento farmacológico , Conservación de Tejido , Animales , Antioxidantes/metabolismo , Frío , Modelos Animales de Enfermedad , Femenino , Humanos , Peroxidación de Lípido , Hígado/metabolismo , Trasplante de Hígado , Mitocondrias/metabolismo , Plastoquinona/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismoRESUMEN
Pretreatment of rats with cytosol of fetal tissue or its thermostable fraction prevented death of animals from CCl4 intoxication, decreased serum transaminase activities and level of TBA-reactive products, and normalized the prooxidant/antioxidant balance in the liver. The effect of cytosol was more pronounced than that of its thermostable fraction.