The effect of nitrone spin trapping agents on red cell glucose metabolism

The nitrone spin trapping agents, 5,5-dimethyl-1-pyrroline-N-oxide and N-t-butyl-alpha-phenyl-nitrone, affect the metabolism of glucose by red cells. Both nitrone spin trapping agents have a dose-dependent inhibitory effect on the metabolism of glucose via the hexose monophosphate pathway. The formation of lactate and pyruvate via the Embden-Meyerhoff pathway in red cells is not significantly affected by treatment with 5,5-dimethyl-1-pyrroline-N-oxide, whereas, treatment with N-t-butyl-alpha-phenylnitrone supresses pyruvate and stimulates lactate formation. These results suggest that nitrone spin trapping agents inhibit the hexose monophosphate pathway in red cells. Since the stimulation of the flux of glucose oxidised via this pathway is thought to be important in the ability of red cells to respond to oxidative stress, the treatment of red cells with spin trapping agents appears to inhibit the cellular protective (antioxidant) response. The use of nitrone spin trapping agents in the study of red cells under oxidative stress (imposed by the spontaneous autoxidation of metabolites or by drug-induced processes) is predicted to exaggerate the degree of oxidative damage by virtue of the inhibitory effort of nitrone spin traps on the hexose monophosphate shunt.