RESUMEN
Two agents possessing hydroxyl radical scavenger activity, dimethyl sulfoxide and tris(hydroxymethyl)aminomethane, increased the production of lactate plus pyruvate in rat hepatocytes cultured for 2 hours. Enhancement of lactate plus pyruvate formation was no longer observed in rat hepatocytes cultured for 24 hours. The formation of CO2 from glucose and from glycerol in suspensions of freshly isolated rat hepatocytes was also enhanced by the two hydroxyl radical scavengers. These results suggest that glycolysis in hepatocytes is suppressed by hydroxyl radicals formed endogenously due to oxidant stress resulting from cell isolation and that the suppression can be relieved by antioxidants.
Asunto(s)
Dióxido de Carbono/metabolismo , Dimetilsulfóxido/farmacología , Depuradores de Radicales Libres/farmacología , Glicerol/metabolismo , Glucólisis/efectos de los fármacos , Radical Hidroxilo/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Trometamina/farmacología , Animales , Radioisótopos de Carbono , Células Cultivadas , Glucosa/metabolismo , Ácido Láctico/metabolismo , Masculino , Ácido Pirúvico/metabolismo , Ratas , Ratas WistarRESUMEN
The lipophilic iron chelator 1,10-phenanthroline has been used in mechanistic studies on intracellular oxidant damage because iron is assumed to play a role in the endogenous formation of highly reactive oxygen species. This study shows that 1,10-phenanthroline has enzyme-modulatory properties in addition to its antioxidant activity. In rat hepatocytes, 1,10-phenanthroline caused inhibition of respiration and enhancement of cellular ATP content, pyruvate release and CO2 formation from glycerol resulting from a modulatory action of 1,10-phenanthroline on various enzymes involved in cellular energy metabolism. In intact mitochondria and in submitochondrial particles, oxygen consumption, complex I activity, and ATPase degradation are inhibited by 1,10-phenanthroline. In submitochondrial particles, complex II activity can also be suppressed by 1,10-phenanthroline. The purified cytosolic enzymes lactate dehydrogenase and glycerol-3-phosphate dehydrogenase are inhibited while purified glyceraldehyde-3-phosphate dehydrogenase is activated by 1,10-phenanthroline. The results suggest that 1,10-phenanthroline modulates various enzyme activities linked to cellular energy metabolism and that this property must be taken into account when using 1,10-phenanthroline as a tool in experiments on oxidant effects in cells.
