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      Native and Oxidized Low–Density Lipoproteins Enhance Superoxide Production from Diabetic Rat Glomeruli


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          Oxygen free radicals have been implicated in mediating diabetic complications, and patients with diabetic nephropathy frequently show increased levels of circulating and oxidized low–density lipoproteins (LDL). In the present study, we measured the superoxide production of glomeruli isolated from poorly controlled diabetic (streptozotocin) rats sacrificed 1 week and 1, and 3 months after the induction of diabetes. The animals were stimulated with native and oxidized LDL isolated from normal humans with normolipidemia. The superoxide ion was measured by using a spectrophotometer. The results demonstrated that the poorly controlled diabetic rat glomeruli showed a significantly higher production of superoxide than normal glomeruli under basal conditions, and this production increased further with the progression of diabetes. Stimulation with either LDL or oxidized LDL enhanced superoxide production by diabetic glomeruli, with oxidized LDL being more potent than LDL. Our results suggest that oxidized LDL may play important roles in the pathogenesis of diabetic nephropathy through enhanced generation of oxygen free radicals.

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          Increased oxidizability of plasma lipoproteins in diabetic patients can be decreased by probucol therapy and is not due to glycation.

          Atherosclerosis is considered to be the major complication of diabetes mellitus. Since diabetic patients have increased blood levels of lipid peroxidation products we investigated whether the susceptibility of blood components to oxidation is altered in this disease. We analysed the parameters characterizing the extent of oxidative change and the antioxidant status of low density lipoprotein (LDL) and high density lipoprotein (HDL) in a group of diabetic patients and in a control population. LDL oxidizability was significantly higher for patients (P = 0.001) than for individuals in the control group. There were no significant differences in the alpha-tocopherol content or levels of performed peroxides in LDL samples isolated from diabetic patients and control individuals which could account for this effect. Similarly, LDL glycation, common in diabetes mellitus, was not responsible, since LDL glycated in vitro was more rather than less resistant to oxidation. Even the presence of unbound glucose at normal or elevated physiological concentrations had a delaying effect on the oxidation of LDL. The increased oxidizability of LDL isolated from diabetic patients could be reduced to control levels by a 6-week standard treatment with Probucol, originally applied to reduce their blood cholesterol.
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            Regulation of Heparin Binding-Epidermal Growth Factor-like Growth Factor Gene Expression by LDL and Oxidized LDL in Rat Mesangial Cells


              Author and article information

              Kidney Blood Press Res
              Kidney and Blood Pressure Research
              S. Karger AG
              24 March 2000
              : 23
              : 2
              : 133-137
              Departments of aInternal Medicine and bBiology, Kaohsiung Medical College, Kaohsiung, Taiwan
              25966 Kidney Blood Press Res 2000;23:133–137
              © 2000 S. Karger AG, Basel

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              Page count
              Figures: 5, References: 23, Pages: 5
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/25966
              Self URI (text/html): https://www.karger.com/Article/FullText/25966
              Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology
              Fourth Asian Nephrology Forum

              Cardiovascular Medicine,Nephrology
              Superoxide,Diabetic rat glomeruli,Low–density lipoproteins


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