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• W2067356075 startingPage "309" @default.
• W2067356075 abstract "Both reactive oxygen species (ROS) and endothelin-1 (ET-1) have been implicated in the pathophysiology of diabetic nephropathy. The interrelationship between them, however, has not been documented in this disease. To determine whether ROS regulates ET-1 production in diabetic kidneys, we examined the in vitro and in vivo effects of ROS donors and scavengers on ET-1 production of diabetic rat glomeruli. For in vitro study, the glomeruli were isolated with a sieving method from streptozotocin-induced diabetic rats and killed at 1 week, 1 month, and 3 months, respectively. Superoxide was measured by a spectrophotometer, and ET-1 was measured by radioimmunoassay. The results demonstrated that the basal production levels of superoxide and ET-1 were higher in diabetic glomeruli than in normal glomeruli in vitro. There was a positive correlation between the production of superoxide and ET-1 in diabetic glomeruli. The basal ET-1 production was markedly attenuated by ROS scavengers including superoxide dismutase, catalase, dimethyl sulf- oxide, and deferoxamine in diabetic glomeruli. Exogenous ROS generated by xanthine/xanthine oxidase significantly enhanced ET-1 generation by both diabetic and normal glomeruli. A high glucose concentration (500 mg/dL) in vitro increased ET-1 production by normal glomeruli but not diabetic glomeruli, and insulin partly suppressed ET-1 production by diabetic glomeruli. The in vivo study demonstrated that when diabetic rats were injected daily with superoxide dismutase or catalase after diabetes was induced, the basal production of ET-1 was markedly attenuated after 1 week and 1 month, respectively. These results indicate that exogenously or endogenously derived ROS can enhance ET-1 production by diabetic rat glomeruli and that ROS scavengers suppress ET-1 production both in vitro and in vivo. The effects of ROS on ET-1 production of diabetic glomeruli may be partly caused by the effect of hyperglycemia or insulin deficiency. (J Lab Clin Med 2000;135:309-15)" @default.
• W2067356075 created "2016-06-24" @default.
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• W2067356075 date "2000-04-01" @default.
• W2067356075 modified "2023-10-18" @default.
• W2067356075 title "Reactive oxygen species enhances endothelin-1 production of diabetic rat glomeruli in vitro and in vivo" @default.
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• W2067356075 doi "https://doi.org/10.1067/mlc.2000.105616" @default.
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