Aldose reductase inhibitors as pathobiochemical probes.

摘要: In tissues susceptible to damage from chronic diabetes, excess glucose is metabolized by aldose reductase (AR) sorbitol. Originally, AR-catalyzed sorbitol formation (and accumulation) was found in the diabetic lens; cataractogenicity of this process proven preventing cataract with an AR inhibitor (ARI). These findings were extended hypothesis that, tissues, excessive intracellular initiates a cascade metabolic abnormalities which gradually progress loss functional and structural integrity. The pivotal role as trigger for such established their occurrence animals treated ARI. By inference, led concept that inhibition should prevent, arrest, and, possibly, reverse development late sequelae. addition motivating drug-oriented research, ARI provided rationale use ARIs experimental tools probe pathogenesis complications. helping elucidate metabolic, functional, ramifications disposal schemes, addition, define applicability animal models study early pathogenic alterations occurring subjects, may enable discrimination tissue arrestible reversible irreversible abnormalities.