title: Noninvasive evaluation of effects of an aldose reductase inhibitor in rat brain by 19F FDG NMR spectroscopy.
abstract: 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.
mesh_terms: 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*
chemical_list: D007093:Imidazoles; D048289:Imidazolidines; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil