1. Enalaprilat inhibits hydrogen peroxide production by murine mesangial cells exposed to high glucose concentrations
- Author
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I Lampreabe, F Vidal-Vanaclocha, and L M Ruiz-Muñoz
- Subjects
medicine.medical_specialty ,Enalaprilat ,Antioxidants ,Nephropathy ,Mice ,Internal medicine ,medicine ,Animals ,Antihypertensive Agents ,Cells, Cultured ,Protein kinase C ,Transplantation ,Mesangial cell ,biology ,Lipid peroxide ,business.industry ,Angiotensin-converting enzyme ,Hydrogen Peroxide ,medicine.disease ,Angiotensin II ,Glomerular Mesangium ,Glucose ,Endocrinology ,Nephrology ,Catalase ,biology.protein ,business ,medicine.drug - Abstract
ide; protein kinase C; angiotensin converting enzyme; mesangial cell; diabetic nephropathy. Background. Oxidative stress is considered to play a role in the pathogenesis of diabetic nephropathy. Angiotensin-converting enzyme (ACE ) inhibitors are hypotensive drugs with a well-known effect in pre- Introduction venting the progression of chronic renal failure. Their mechanism of action is not clearly established. Several factors (growth hormone, insulin-like growth Methods. The effect of enalaprilat on hydrogen perox- factor-1, transforming growth factor-beta, tumour necide (H 2 O 2 ) production by cultured murine mesangial rosis factor-alpha, interleukin-1 and others) play a role cells exposed to 5.5 (basal condition), 30 and 50 mM in the damaging effects of hyperglycaemia in chronic glucose concentrations was examined over 8 h. A fluo- renal failure of diabetic nephropathy [1,2]. rimetric method quantifying, in arbitrary units, the Hydrogen peroxide (H 2 O 2 ) and other reactive intracellular dichlorofluorescein ( DCFH) oxidation to oxygen metabolites ( ROM) such as superoxide anion the highly fluorescent compound 2’7’dichlorofluoresc- and hydroxyl radical are also mediators of tissue injury ein (DCF ) from the non‐fluorescent probe dichloro- [3]. These reactive species are associated with both fluorescein-diacetate (DCFH-DA) was employed (a immune and non-immune glomerular injury [4,5], method not previously reported for cultured mesangial chronic progression of renal disease [5,6] and also with cells). Experiments were repeated three times in quad- diabetic vascular complications [3,7]. However, little ruplicate wells. information exists regarding a possible role of mesangResults. H 2 O 2 production by mesangial cells exposed ial cell in ROM production in diabetes mellitus. to 50 mM glucose was significantly increased after 1 Recently a significant lipid peroxide production in h, compared to cells exposed to 5.5 and 30 mM glucose. cultured rat glomeruli exposed to high glucose concenThis observation was not reproduced with 50 mM trations has been reported. The proposed biochemical mannitol. Addition of 100 ng/ml enalaprilat to cells pathway is a de novo synthesis of diacylglycerol with 50 mM glucose significantly inhibited H 2 O 2 pro- resulting from hyperglycaemia, leading to an activation duction during the 8 h of the assay. This response was of the protein kinase C ( PKC ) enzyme [8 ]. similar to that obtained with 100 ng/ml catalase. Angiotensin-converting enzyme (ACE ) inhibitors Increasing enalaprilat concentrations (10, 50 and are drugs with significant clinical benefits in the preven100 ng/ml ) also significantly decreased the constitutive tion of chronic renal failure in diabetic nephropathy H 2 O 2 generation in the presence of 5.5 mM glucose. [9]. The mechanism of renal protection, which appears not to be fully related to their hypotensive effect
- Published
- 1997
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