Effects of glucose and SNK-860, an aldose reductase inhibitor, on the polyol pathway and chemiluminescence response of human neutrophils in vitro.
An in vitro incubation study was conducted to investigate whether increased activity of the polyol pathway in human neutrophils under diabetic conditions resulted in a decrease of superoxide anion produced by NADPH oxidase on the membrane of neutrophils. Lucigenin-enhanced chemiluminescence (CL) to phorbol myristate acetate as respiratory burst and sorbitol levels in neutrophils after incubation with glucose and an aldose reductase (AR) inhibitor, SNK-860 (SNK) were measured. Sorbitol levels increased from 0.210 +/- 0.029 nmol 10(7) cells-1 in 5 mmol l-1 glucose to 0.446 +/- 0.036 nmol 10(7) cells-1 in 40 mmol l-1 glucose, while CL decreased from 0.542 +/- 0.034 cpm cell-1 in 5 mmol l-1 glucose to 0.430 +/- 0.018 cpm cell-1 in 40 mmol l-1 glucose. The addition of 10 mumol l-1 SNK normalized the increased sorbitol levels in neutrophils exposed to 40 mmol l-1 glucose and improved, but did not normalize, the decrease in CL induced by 40 mmol l-1 glucose (p < 0.001). Galactose (40 mmol l-1) also reduced CL, which was improved by the addition of SNK (p < 0.01). These results suggest that impaired respiratory burst induced by high-glucose concentrations is caused by competition for NADPH resulting from increased polyol pathway activity and/or glycation and that an AR inhibitor may be capable in part of preventing increased susceptibility to infection in diabetic patients.
Kawamura
T
T
Research Division of Health Examination Centre, Chubu Rosai Hospital, Nagoya, Japan.
Suzuki
K
K
Matsumae
H
H
Sano
T
T
Sakamoto
N
N
Hotta
N
N
D000328:Adult; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D005690:Galactose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008163:Luminescent Measurements; D008353:Mannitol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D012016:Reference Values; D013012:Sorbitol / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001786:Blood Glucose; D007093:Imidazoles; D048289:Imidazolidines; D008353:Mannitol; D013012:Sorbitol; C077139:fidarestat; D000449:Aldehyde Reductase; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D005690:Galactose