title: Effects of glucose and SNK-860, an aldose reductase inhibitor, on the polyol pathway and chemiluminescence response of human neutrophils in vitro.
abstract: 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.
authors.affiliation: Research Division of Health Examination Centre, Chubu Rosai Hospital, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawamura
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Matsumae
authors.forename: T
authors.initials: T
authors.lastname: Sano
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
authors.forename: N
authors.initials: N
authors.lastname: Hotta
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007093:Imidazoles; D048289:Imidazolidines; D008353:Mannitol; D013012:Sorbitol; C077139:fidarestat; D000449:Aldehyde Reductase; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D005690:Galactose