Noninvasive evaluation of effects of an aldose reductase inhibitor in rat brain by 19F FDG NMR spectroscopy.
The inhibitory effects of an aldose reductase inhibitor, sorbinil (Pfizer, NY), on cerebral glucose metabolism were investigated noninvasively in rat brain using 19F nuclear magnetic resonance (NMR) spectroscopy and 2-fluoro-2-deoxy-D-glucose (2-FDG). Sorbinil given orally in the daily recommended doses (25 mg/kg) for man for the treatment of diabetic complications inhibited 2-FDG flux into the aldose reductase sorbitol (ARS) pathway, demonstrated as a reduction in the intensity of the ARS index resonance as well as an increase in the resonance area ratio between the pentose monophosphate shunt (PMS) and ARS index resonances (PMS/ARS ratio). Spatial metabolite mapping using rotating frame one-dimensional zeugmatography indicated that the inhibitory effect is spatially nonspecific. The present study is the first direct noninvasive observation of the effects of a pharmacological agent on cerebral enzymatic activities.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003847:Deoxyglucose / Q000031:analogs & derivatives; D019788:Fluorodeoxyglucose F18; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil