Effect of tolrestat, an aldose reductase inhibitor, on neutrophil respiratory burst activity in diabetic patients

Metabolism: Clinical and Experimental
S H IhmC J Park

Abstract

One hypothesis for the reduction in oxidative killing of neutrophils in diabetic patients is that increased polyol pathway activity during hyperglycemia reduces intracellular levels of nicotinamide adenine dinucleotide phosphate (NADPH), resulting in the reduction of neutrophil superoxide production during the respiratory burst. To test this hypothesis, we assessed the effect of tolrestat, an aldose reductase inhibitor, on neutrophil respiratory burst activity (NRBA) in diabetic patients. We measured fasting plasma glucose (FPG), hemoglobin A1 (HbA1), and NRBA levels in 79 diabetic patients and 48 normal controls. NRBA was reassessed in 34 patients after 4 weeks of tolrestat or placebo treatment, in seven controls after 4 weeks of tolrestat treatment, and in seven patients after 4 weeks of blood glucose control. NRBA was determined by flow cytometry, which detected fluorescent 2',7'-dichlorofluorescein (DCF) in neutrophils formed from 2',7'-dichlorofluorescein diacetate (DCF-DA) during phorbol myristate acetate (PMA)-induced respiratory bursts. Diabetic patients showed lower NRBA than the normal controls (mean cellular fluorescence, 438 +/- 103 v 668 +/- 101, mean +/- SD, P < .001). NRBA in diabetic patients showed a negative c...Continue Reading

Citations

Dec 30, 2010·Journal of Periodontology·Peter F KadorRichard A Reinhardt
Apr 16, 2021·Endocrinology, Diabetes & Metabolism·Lina MerjanehMargaret Rosenfeld

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